July 10, 2017
Bristol-Myers Squibb announced promising interim data from its phase III clinical trial of Opdivo 3mg/kg compared to 10mg/kg Yervoy in melanoma. In patients with stage IIIb/c or stage IV melanoma who are at high risk of recurrence after complete surgical resection, Opdivo met its primary endpoint at the planned interim analysis. The endpoint was superior recurrence-free survival (RFS). “These topline results support the potential promise of Opdivo as a treatment option for patients with high-risk surgically resected melanoma,” Vicki Goodman, BMS’ development lead for Melanoma and Genitourinary Cancer, said in a statement. “There remains an unmet need for additional options as the majority of stage III and resected stage IV high-risk melanoma patients experience disease recurrence after surgery. ” The trial is CheckMate-238, which involves 906 patients receiving either Opdivo or Yervoy. The company’s statement did not release any data, but plans to present it at a future medical conference.
June 12, 2017
Hutchison China MediTech (Chi-Med) announced results from its pivotal phase III trial with fruquintinib in patients with locally advanced or metastatic colorectal cancer (CRC). The FRESCO trial is a randomized, double-blind, placebo-controlled, multicenter trial. Enrollment was completed in May 2016; 519 patients were screened. The intention-to-treat (ITT) population of 416 patients was randomized at a 2:1 ratio to receive either: 5mg of fruquintinib orally once per day, on a three-weeks-on/one-week-off cycle, plus BSC (278 patients); or placebo plus BSC (138 patients). Randomization was stratified for prior anti-VEGF therapy and K-Ras gene status. The primary endpoint of median overall survival (OS) was 9.30 months [95% CI 8.18–10.45] in the fruquintinib group vs. 6.57 months [95% CI 5.88–8.11] in the placebo group, with a hazard ratio of 0.65 [95% CI: 0.51–0.83; two-sided p<0.001]. The secondary endpoint of median progression-free survival (PFS) was 3.71 months [95% CI 3.65–4.63] in the fruquintinib group vs. 1.84 months [95% CI 1.81–1.84] in the placebo group, with a hazard ratio of 0.26 [95% CI: 0.21–0.34; two-sided p<0.001]. Chi-Med expects to complete the New Drug Application (NDA) submission for fruquintinib to the China Food and Drug Administration imminently. The company also expects to initiate U.S. clinical studies in 2017.
May 22, 2017
Photocure released phase III study results of Blue Light Flexible Cystoscopy (BLFC) with Hexvix/Cysview for bladder cancer. The study was a prospective, open, comparative, within-patient controlled study, and included 304 patients with non-muscle invasive bladder cancer (NMIBC) enrolled at 17 academic institutions in the US. In the study, BLFC with Cysview was used with the Karl Storz D-Light C PDD Flexible Videoscope System. The study showed that BLFC with Cysview detected bladder cancer recurrence in 21.5% of the patients undergoing surveillance cystoscopy that otherwise would have been missed with white light (WL) alone, which is highly significant (p<0.0001). Of note, the study showed that nine out of 26 patients (34.6%) with flat, more aggressive high grade lesions (carcinoma in situ; CIS) were diagnosed using confirmatory Blue Light Cystoscopy with Cysview alone and not WL (p<0.0001). The study also showed that there was no increase in the rate of related adverse events after repeated administration of Cysview in bladder cancer patients undergoing cystoscopy examination. The company intends to submit the data to the FDA to seek approval of BLFC with Cysview in the surveillance setting in the U.S., and an expansion of the indication to include CIS.
May 1, 2017
Eli Lilly issued results of an interim analysis for MONARCH 3, a phase III study evaluated abemaciclib in combination with an aromatase inhibitor (letrozole or anastrozole) compared to treatment with an aromatase inhibitor alone in women with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. The global, double-blind, placebo-controlled study enrolled 493 patients randomized to receive 150mg of abemaciclib or placebo orally twice a day without interruption, given in combination with either 1mg of anastrozole or 2.5mg of letrozole once daily until disease progression or unacceptable toxicity. Adverse events were generally consistent with previous studies of abemaciclib, with the most common adverse events being diarrhea, neutropenia, fatigue and nausea. Following the MONARCH 3 interim analysis, Eli Lilly intends to begin global submissions of the results in the third quarter of 2017. In addition, Lilly intends to initiate MONARCH 1 and MONARCH 2 submissions beginning in the second quarter of 2017.
April 24, 2017
OncoMed Pharmaceuticals issued results of a 145-patient, phase II trial of tarextumab (anti-Notch2/3, OMP-59R5) in combination with etoposide plus either cisplatin or carboplatin chemotherapy in previously untreated patients with extensive-stage small cell lung cancer. The double-blind, multicenter trial randomized two study arms that received either 15mg/kg of tarextumab every three weeks in combination with six cycles of etoposide and either cisplatin or carboplatin chemotherapy followed by tarextumab maintenance to progression or six cycles of chemotherapy and a placebo. The median progression-free survival (mPFS) for tarextumab plus chemotherapy was 5.6 months versus 5.5 months for chemotherapy plus placebo (HR=0.969). The median overall survival (mOS) analysis did not show a benefit for tarextumab in combination with chemotherapy (mOS=9.3 months) compared to the chemotherapy plus placebo arm (10.3 months; HR=1.01). Five individual Notch biomarkers (Hes1, Hes6, Hey1, Hey2 and Notch3) failed to identify a definitive subset of patients with a treatment effect on either mPFS or mOS. Overall response rates were 68.5% and 70.8% in the tarextumab and placebo arms respectively. The combination of tarextumab plus chemotherapy was well-tolerated.
April 10, 2017
Immunomedics released results of a phase II study of sacituzumab govitecan (IMMU-132) in patients with advanced and heavily pretreated metastatic small-cell lung cancer (SCLC). A total of 53 patients with metastatic SCLC were enrolled into the open-label phase II study after receiving a median of two prior lines of therapy (range, one to seven). All patients had previously received cisplatin or carboplatin plus etoposide, and were considered chemosensitive (n=27, 51%) or chemoresistant (n=26, 49%) to their platinum-containing frontline therapy, based on a duration of response of more than three months or less than three months, respectively. Treatments with sacituzumab govitecan were administered at a dose of either eight or 10 mg/kg on days one and eight of 21-day cycles. The primary endpoints were safety and objective response rate (ORR), with duration of response, progression-free survival (PFS) and overall survival (OS) as secondary endpoints. Sixty percent of patients showed tumor shrinkage from baseline measurements using computed tomography (CT). On an intention-to-treat (ITT) basis (n=50), the ORR was 14% (17% for the 10mg/kg group) and the median response duration was 5.7 months (95% confidence interval [CI], 3.6 to 19.9 months). Clinical benefit rate (CBR) at four months was 34%, with median PFS and median OS at 3.7 months (95% CI, 2.1 to 4.3 months) and 7.5 months (95% CI, 6.2 to 8.8 months), respectively. There was no statistical difference in ORR, PFS or OS between those patients who were chemosensitive or chemoresistant to first-line chemotherapy, but the CBR was 50% and 26%, respectively. There was a statistically significant higher OS in those patients who received prior topotecan versus no topotecan therapy.
March 27, 2017
Eli Lilly issued results of a phase III trial of abemaciclib in combination with fulvestrant in women with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced breast cancer who have relapsed or progressed after endocrine therapy. The global, double-blind study had an intent-to-treat population of 669 patients randomized to receive abemaciclib or placebo orally twice a day on a continuous dosing schedule, given in combination with fulvestrant at its approved dose and schedule, until disease progression. Patients enrolled in the study had experienced disease progression on or within 12 months of receiving endocrine treatment in the neoadjuvant or adjuvant setting or while receiving first-line endocrine therapy for metastatic disease. Patients who had received chemotherapy in the metastatic setting were not eligible for the study. The most common adverse events observed were diarrhea, neutropenia, nausea and fatigue, and were consistent with the previous studies of abemaciclib. Lilly intends to submit a new drug application (NDA) for single-agent abemaciclib in the second quarter of 2017.
March 20, 2017
Advaxis reported results of a phase II trial of axalimogene filolisbac for the treatment of persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC). GOG-0265 is an open-label, single-arm, two-stage study. Patients who progressed on or after at least one prior line of systemic-dose chemotherapy receive one cycle (three doses) of axalimogene filolisbac at 1 x 109 CFU every 28 days. The final efficacy results of GOG-0265 demonstrated that 38% of patients (n=19/50) with heavily pretreated PRmCC were alive 12 months following treatment with axalimogene filolisbac. The GOG-0265 study protocol used a logistic model-based calculation to establish the expected 12-month survival rate. The model identified the key prognostic factors of age, race and performance status significantly related to survival from a database of approximately 500 patients with PRmCC who participated in 17 previous phase II studies conducted by the Gynecologic Oncology Group (GOG), now part of NRG Oncology. Using this model, the expected 12-month survival rate of patients enrolled in the study was calculated to be 24.5%. As a result, the 38% 12-month survival rate of patients treated with axalimogene filolisbac represents a 52% improvement over the expected survival rate and is the highest 12-month survival rate achieved to date in this setting. The probability of this survival improvement being detected by chance versus a true treatment effect was calculated to be 0.02. A compelling and ongoing complete response of 18.5 months was observed and the longest ongoing survival is 40.6 months. Advaxis plans to initiate a global, phase III, randomized registration study in patients with metastatic cervical cancer later this year.
AstraZeneca released results of a phase III trial of Lynparza (olaparib) tablets (300mg twice daily), compared with placebo in the maintenance setting for germline BRCA-mutated (gBRCA), platinum-sensitive, relapsed ovarian cancer. The trial met its primary endpoint of investigator-assessed progress-free survival (PFS) (HR 0.30; 95% CI 0.22-0.41; p<0.0001; median 19.1 months vs 5.5 months). PFS as measured by Blinded Independent Central Review (BICR) evaluation, a pre-specified sensitivity analysis supporting the primary endpoint, demonstrated a median PFS of 30.2 months vs 5.5 months for placebo, representing an improvement of 24.7 months (HR 0.25; 95% CI 0.18-0.35; p<0.0001). Additionally, a statistically-significant benefit in time to second progression or death (PFS2) was also seen in patients treated with Lynparza (HR 0.50; 95% CI 0.34-0.72; p=0.0002; median not reached vs 18.4 months), compared with placebo, as well as improvements in other key secondary endpoints. The most common hematological AEs reported in the Lynparza arm versus placebo were anemia (43.6% vs 8.1%), neutropenia (19.5% vs 6.1%), and thrombocytopenia (13.8% vs 3.0%). Grade ≥3 hematological AEs reported in the Lynparza arm versus placebo were anemia (19.5% vs 2.0%), neutropenia (5.1% vs 4.0%) and thrombocytopenia (1.0% vs 1.0%).
March 6, 2017
Amgen reported results of a phase III head-to-head ENDEAVOR trial of Kyprolis (carfilzomib) and dexamethasone (Kd) for the treatment of relapsed or refractory multiple myeloma. The randomized, open label study enrolled 929 patients and evaluated Kyprolis in combination with low-dose Kd versus Velcade (bortezomib) with low-dose dexamethasone (Vd) in patients whose multiple myeloma has relapsed after at least one, but not more than three, prior therapeutic regimens. The primary endpoint of the trial was progression-free survival (PFS), defined as the time from treatment initiation to disease progression or death. Patients received treatment until progression with Kyprolis as a 30-minute infusion on days one, two, eight, nine, 15 and 16 of 28-day treatment cycles, along with low-dose dexamethasone (20mg). For cycle one only, Kyprolis was administered at 20mg/m2 on days one and two, and if tolerated was escalated to 56mg/m2 from day eight cycle one onward. Patients who received bortezomib (1.3mg/m2) with low-dose Vd (20mg) were treated with bortezomib administered subcutaneously or intravenously at the discretion of the investigator and in accordance with regional regulatory approval of bortezomib. The study met the key secondary endpoint of OS, demonstrating that patients with relapsed or refractory multiple myeloma treated with Kyprolis (carfilzomib) and Kd lived 7.6 months longer than those treated with bortezomib and Vd (median OS 47.6 months for Kd versus 40 for Vd, HR = 0.79, 95% CI, 0.65 0.96). This Kd regimen administered with 56mg/m2 Kyprolis twice weekly is already approved in the U.S., EU and other countries based on the primary analysis of PFS in the ENDEAVOR study.
Augmenix reported results of a phase III trial of SpaceOAR System hydrogel for maintaining sexual function and potency following intensity modulated radiation therapy (IMRT) during prostate radiotherapy. Studies have shown a correlation between radiation dose to the penile bulb, a structure at the base of the penis, and post-radiotherapy impotence. In the SpaceOAR System trial, the median radiation dose to the penile bulb was reduced by 49% in SpaceOAR treated patients (21 Gy for Control vs. 11 Gy for SpaceOAR treated, p=0.036). Among men who were potent at baseline, the analysis showed that SpaceOAR treated men were better able to maintain erections sufficient for intercourse through three years of follow-up (p=0.03). Of the men treated with SpaceOAR, 66.7% were able to have erections sufficient for intercourse at three years compared to 37.5% in the Control arm, a 77.8% improvement.
February 27, 2017
OncoGenex Pharmaceuticals reported results of apatorsen in two randomized phase II clinical trials for bladder and prostate cancer. The Borealis-2 trial evaluated apatorsen in combination with docetaxel treatment in 200 patients with metastatic bladder cancer whose disease had progressed following first-line platinum-based chemotherapy. Patients who received apatorsen treatment experienced a 20% reduction in risk of death, compared to patients receiving docetaxel alone (overall survival hazard ratio (HR)=0.80; 80% CI: 0.65-0.98; p=0.078). Partial or complete responses occurred in 16.2% patients receiving apatorsen plus docetaxel compared to 10.9% patients receiving docetaxel alone with median response durations of 6.2 months versus 4.4 months, respectively. Higher baseline serum heat shock protein 27 (Hsp27) levels were significantly prognostic for indicating an almost two-fold higher risk of death (HR=1.96; p=0.0001). In an exploratory analysis on a subset of patients (20% of total) who completed at least two treatment cycles and had either a decrease in serum Hsp27 levels from baseline or had only a 20.5% increase in serum Hsp27 levels from baseline, the reduction in risk of death with apatorsen treatment was 71% (HR=0.29: 80% CI: 0.18-0.48; interaction p=0.0727). The Pacific trial evaluated the ability of apatorsen, when added to Zytiga (abiraterone acetate), to reverse or delay treatment resistance in 72 men who were experiencing a rising PSA on Zytiga alone. The primary endpoint evaluated the proportion of patients who were progression free (clinical and radiologic) at study day 60 with apatorsen added to Zytiga, compared to continuing Zytiga alone. In men receiving apatorsen, 33% were progression free at study day 60 compared to 17% for those men receiving Zytiga alone. For patients with five circulating tumor cells (CTCs) at baseline, 22% vs 11% of patients had a CTC reduction to less than five CTCs when apatorsen was added to Zytiga vs Zytiga alone, respectively. Clinical data from trials in bladder and prostate cancers demonstrated apatorsen was well-tolerated and improved patient outcomes when administered in combination with standard-of-care treatments.
February 21, 2017
ASLAN Pharmaceuticals issued results of a phase II study of varlitinib (ASLAN001) in combination with capecitabine as second-line treatment for metastatic HER2-positive breast cancer patients progressing on trastuzumab (Herceptin). The multinational, randomized, open-label study compared the effects of varlitinib combined with capecitabine versus that of lapatinib (Tykerb) combined with capecitabine on tumor shrinkage at week 12. Top-line data showed significantly greater tumor shrinkage at week 12 of the treatment cycle in patients who were on therapy for more than a month, receiving 400mg varlitinib (36.4%) twice daily compared to 1,250mg lapatinib (17.8%) once daily (p=0.075). A total of 50 patients were enrolled in the study. While the study was not powered for objective response rate (ORR), it found that patients dosed with varlitinib showed higher ORR compared to patients on lapatinib (60% versus 46%). There were no differences in progression-free survival (PFS) or overall survival (OS) in the study. Adverse events reported included nausea, vomiting and diarrhoea, and occurred at similar frequency in both arms. The incidence of grade three diarrhea was 12.5% in the varlitinib group and was clinically manageable. There were no instances of grade four diarrhea.
January 16, 2017
Halozyme Therapeutics released results of a phase II study of PEGPH20 in combination with ABRAXANE (nab-paclitaxel) and gemcitabine in stage IV pancreas cancer patients. Stage 2 of the randomized, multicenter study showed a 91% improvement in median PFS for HA-High patients in the PEGPH20 arm, 8.6 months compared to 4.5 months in the control arm and achieved its primary endpoint to evaluate and demonstrate a reduction in the rate of thromboembolic events in the PEGPH20 arm. The company has initiated a phase III clinical trial, HALO 301. HALO 301 is a global, randomized, double-blind, placebo-controlled clinical trial evaluating PEGPH20 for metastatic pancreas cancer. The trial will be conducted at approximately 200 sites with two primary endpoints, progression free survival and overall survival in patients receiving PEGPH20 in combination with gemcitabine and ABRAXANE (nab-paclitaxel) compared to gemcitabine and nab-paclitaxel alone.
December 19, 2016
AOP Orphan Pharmaceuticals and
PharmaEssentia reported results of a
phase III study of ropeginterferon alfa-2b
versus HU in patients with Polycythemia
Vera. PROUD-PV is a phase III, randomized,
open-label, multicenter, controlled, parallel
arm study and is part of the development
program to support marketing authorizations
of ropeginterferon alfa-2b (AOP2014/
P1101) in Europe and in the U.S. The
pre-specified primary endpoint, which
was a composite of Complete Hematologic
Response (CHR) and spleen length normality,
was confounded by the fact that the
median spleen length was almost normal
at baseline and the observed change was
not clinically relevant (21.3% for ropeginterferon
alfa-2b versus 27.6% for HU in the
intent-to-treat-population, p=0.2233). At 12
months, Complete Hematologic Response
(CHR) was achieved in a high proportion
of patients and non-inferiority was
demonstrated (43.1% for ropeginterferon
alfa-2b versus 45.6% for HU in the intentto-
treat-population, p=0.0028). Ropeginterferon
alfa-2b showed significantly better
tolerability than HU. Overall, 59.6% of the
patients in the ropeginterferon alfa-2b arm
experienced treatment-related adverse
events compared to 75.6% of the patients
treated with HU (p<0.05). There was no
difference in adverse events of special interest
concerning interferons (auto-immune,
psychiatric) or concerning PV (cardiovascular
AstraZeneca issued results of a phase III
study of TAGRISSO (osimertinib) for epidermal
growth factor receptor (EGFR) T790M
mutation-positive metastatic non-small cell
lung cancer (NSCLC). AURA3 data showed
TAGRISSO offered a statistically significant
improvement in PFS versus standard platinum-
based doublet chemotherapy (10.1
months vs 4.4 months, hazard ratio [HR]
0.30; 95% confidence interval (CI): 0.23, 0.41;
p<0.001). In an investigator-assessed, prespecified
exploratory subgroup analysis of
34% of patients with central nervous system
(CNS) metastases at baseline, PFS was 8.5
months with TAGRISSO versus 4.2 months
with platinum-pemetrexed chemotherapy
(HR 0.32; 95% CI: 0.21, 0.49). The AURA3
safety data for TAGRISSO were in line with
previous experience. Grade =3 drug-related
adverse events (AEs) were reported in 6% of
patients (n=16) treated with TAGRISSO and
34% (n=46) treated with platinum-based
doublet chemotherapy. The most common
drug-related AEs in the TAGRISSO group,
were diarrhea (29% overall; 1% Grade =3)
and rash (28% overall; <1% Grade =3) and,
in the chemotherapy group, they were
nausea (47% overall; 3% Grade =3) and
decreased appetite (32% overall; 3% Grade
=3). TAGRISSO was granted accelerated
approval by the FDA in November 2015,
conditional marketing authorization by the
EMA in February 2016, approval in Japan in
March 2016 and is currently under Fast Track
review in China.
November 21, 2016
Ascend Biopharmaceuticals issued results of a phase I/IIa trial of ASN-002 in nodular basal cell carcinoma (nBCC). The trial is designed to assess the safety, tolerability and response of intra-tumoral injections of ASN-002 in 24 adult patients with nodular basal cell carcinoma. The trial design includes 3 cohorts where escalating doses of ASN-002 were administered via injection into the tumor. All cohorts received one injection per week for three weeks with follow-up visits at weeks four, eight, 12 and 16. The primary endpoints for all cohorts are clinical and histological clearance and overall safety. Results showed that the treatment has a favorable safety profile and demonstrated encouraging signs of efficacy. The complete response (CR) rate in the high dose cohort was 100%. In the second medium dose cohort, 67% of patients achieved a CR with 33% achieving a partial response. The overall objective response rate observed for the medium and high doses was 100% and at the lowest dose administered, 33% of patients achieved a CR.
November 14, 2016
Lexicon Pharmaceuticals reported results of a phase III study of telotristat ethyl in patients with carcinoid syndrome. TELESTAR was a global, double-blind study that enrolled 135 patients from 12 countries with carcinoid syndrome whose symptoms were not adequately controlled on somatostatin analog therapy (SSA), the current standard of care. Data show that patients who added telotristat ethyl to SSA therapy at both the 250mg and 500mg doses experienced a statistically significant reduction from baseline compared to placebo in the average number of daily bowel movements over the 12-week study period (p<0.001), meeting the study’s primary endpoint. There was also a statistically significant reduction in the levels of urinary 5-hydroxyindole acetic acid (5-HIAA), the main metabolite of serotonin, from baseline to week 12 with a reduction of 40mg/24 hours (250mg arm) and 58mg/24 hours (500mg arm) versus an increase of 11mg/24 hours in the placebo arm (p<0.001). Treatment with telotristat ethyl was generally well-tolerated during the double-blind treatment period. Eighty-five percent of the patients originally enrolled in TELESTAR opted to continue study participation, receiving treatment with 500 mg telotristat ethyl in a 36-week open-label extension (OLE) study.
October 24, 2016
OncoGenex Pharmaceuticals released results of a phase III trial of custirsen in patients whose non-small cell lung cancer (NSCLC) has progressed following initial treatments. The ENSPIRIT trial is an international, randomized, open-label trial. The trial investigated if combining custirsen with docetaxel, a standard second-line NSCLC chemotherapy, has the potential to improve survival outcomes compared to docetaxel alone in these patients. The trial enrolled 664 patients at approximately 50 sites globally. The trial did not meet the primary endpoint of demonstrating a statistically significant improvement in overall survival for patients treated with custirsen in combination with docetaxel compared to docetaxel alone. The median overall survival for the custirsen arm was nine months versus 7.9 months for the control arm with a hazard ratio of 0.915 (one-sided p=0.178). Safety results were consistent with those observed in previous trials of custirsen in combination with chemotherapy.
October 17, 2016
Merrimack Pharmaceuticals reported results
of a phase III study of Onivyde (irinotecan liposome
injection) in combination with fluorouracil
(5-FU) and leucovorin for patients with metastatic
pancreatic ductal adenocarcinoma (mPDAC) following
treatment with gemcitabine-based therapy.
The overall survival advantage of Onivyde
in combination with 5-FU and leucovorin versus
5-FU and leucovorin alone was maintained in this
extended analysis: 6.2 months versus 4.2 months
(p=0.039, hazard ratio (HR) =0.75, 95% CI: [0.057-
0.99]). The probability of survival at one year was
greater in the Onivyde combination arm of the
study when compared to the 5-FU and leucovorin
arm: 12-month overall survival estimates of
26% (95% CI, 18-35%) were observed in the
Onivyde combination treatment arm compared
to 16% (95% CI, 10-24%) for 5-FU and leucovorin
arm. The overall response rate (ORR) for the
Onivyde plus 5-FU and leucovorin arm was 16%
versus 1% for the 5-FU and leucovorin arm
(p<0.0001). Treatment with Onivyde in combination
with 5-FU and leucovorin provided a
two-fold improvement in disease control rate
compared with 5-FU and leucovorin alone (52%
v. 24%, respectively). Final results suggest that
patients treated with Onivyde in combination
with 5-FU and leucovorin had no notable deterioration
in quality of life at 12 weeks despite the
addition of a second chemotherapeutic agent
to 5-FU and leucovorin. No new safety concerns
were noted and the overall safety profile was
manageable with the most common grade three
adverse events of neutropenia, diarrhea, fatigue,
vomiting and asthenia.
September 6, 2016
Nymox Pharmaceutical reported results of a phase III trial of fexapotide in late stage development for enlarged prostate (BPH) and for localized prostate cancer. Long-term outcomes were determined in 391 patients who were given double-blind placebo injections, which were followed by crossover to other treatments at the patients’ discretion. The numbers of blinded placebo patients who subsequently received surgical treatment during the next two to three years for their BPH symptoms were then prospectively analyzed. Results have now shown that there was an 82 to 95% reduction in the number of these patients who required surgery after they received crossover fexapotide in the trial, as compared to patients who did not receive fexapotide but instead received crossover, conventionally approved BPH treatments (p<0.0001).
July 11, 2016
Bayer reported results of a phase III trial of Stivarga (regorafenib) for patients with unresectable hepatocellular carcinoma (HCC) who progressed after treatment with Nexavar (sorafenib) tablets. The RESORCE trial was a randomized, double blind, placebo controlled, multicenter study enrolling 573 patients randomized in a 2:1 ratio to receive either regorafenib plus best supportive care (BSC) or placebo plus BSC. Patients received 160mg regorafenib once daily, for three weeks on/one week off, or placebo. Median progression-free survival was 3.1 months in patients taking regorafenib v. 1.5 months in the control group (HR 0.46; 95% CI 0.370.56; p<0.001). Median time to progression was 3.2 v. 1.5 months (HR 0.44; 95% CI 0.360.55; p<0.001). Disease control rate (composed of complete or partial response and stable disease) was 65.2% v. 36.1%, respectively (p<0.001). Overall response rates (complete and partial response) were 10.6% v. 4.1% (p=0.005), respectively. Bayer plans to submit data from the RESORCE study as the basis for marketing authorization of regorafenib in the treatment of unresectable HCC in the U.S. and other markets worldwide in 2016.
July 4, 2016
Celator Pharmaceuticals issued results of
a phase III trial of VYXEOS (cytarabine: daunorubicin)
Liposome for Injection (CPX-351) in
patients with high-risk acute myeloid leukemia
(AML). The randomized, controlled trial enrolled
309 patients, and compared VYXEOS to
the conventional cytarabine and daunorubicin
treatment regimen (commonly referred to as
7+3) as first-line therapy in older (60-75 years
of age) patients. Patients were randomized 1:1
to receive either VYXEOS or 7+3. First induction
for VYXEOS was 100u/m2; days one, three
and five by 90-minute infusion, and for the
control arm was cytarabine 100mg/m2/day by
continuous infusion for seven days and daunorubicin
60mg/m2 on days one, two and three
(7+3). Second induction for VYXEOS-treated
patients was 100u/m2 on days one and three,
and the control arm was cytarabine 100mg/
m2/day by continuous infusion for five days
and daunorubicin 60mg/m2 on days one and
two (5+2). An improvement in overall survival
was also observed in FLT3 mutated patients
with median overall survival of 10.25 months
in the VYXEOS arm compared to 4.55 months
in the 7+3 arm. The Hazard Ratio (HR) was
0.57 (p=0.093). In addition, preliminary data
on NPM1 and CEBP mutations were presented
showing an improvement in response rate and
overall survival in patients with these mutations.
The company expects to submit a NDA
for VYXEOS with the FDA by the end of the
third quarter of 2016.
June 13, 2016
Array BioPharma released results of a phase II trial of encorafenib for BRAF-mutant colorectal cancer. In the phase II trial, 102 patients were randomized 1:1 to receive encorafenib and cetuximab with or without alpelisib. Median PFS was 5.4 months and 4.2 months for the triplet and doublet regimens, respectively. An early analysis of median OS exceeded one year for the triplet regimen and was not reached for the doublet regimen. Confirmed ORR was 27% (95% CI, 16-41%) for the triplet regimen and 22% (95% CI, 12-36%) for the doublet regimen. Grade 3/4 AEs occurring in greater than 10% of patients in either arm included anemia, hyperglycemia and increased lipase. Historical published PFS and OS results after first-line treatment range between 1.8 to 2.5 months and four to six months, respectively, and published response rates from various studies in this population range between 6% to 8%.
Genmab reported results of a phase III POLLUX study (MMY3003) of daratumumab in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. The study enrolled 569 patients who had relapsed or refractory multiple myeloma. The trial met the primary endpoint of improving progression free survival (PFS) at a pre-planned interim analysis (Hazard Ratio (HR)=0.37 (95% CI 0.27-0.52), p<0.0001). Patients who received treatment with daratumumab in combination with lenalidomide and dexamethasone had a 63% reduction in risk of their disease progressing, compared to those who did not receive daratumumab. The median PFS for patients treated with daratumumab in combination with lenalidomide and dexamethasone has not been reached, compared to an estimated median PFS of 18.4 months for patients who received lenalidomide and dexamethasone alone. Based on the results at the pre-planned interim analysis conducted by an Independent Data Monitoring Committee (IDMC), it was recommended that the data be unblinded. Patients originally assigned to the lenalidomide plus dexamethasone alone treatment group will be offered the option of receiving daratumumab monotherapy following confirmed disease progression.
June 6, 2016
Array BioPharma released results of a
phase III trial of binimetinib for NRAS-mutant
melanoma. In the trial, 402 patients with
NRAS-mutant melanoma were randomized
2:1 to receive binimetinib or dacarbazine,
respectively. The primary endpoint of PFS
was met, with a hazard ratio of 0.62, [95% CI
0.47-0.80] and a p-value of less than 0.001.
The median PFS on the binimetinib arm
was 2.8 months versus 1.5 months on the
dacarbazine arm. Importantly, an improvement
in median PFS in binimetinib-treated
patients was observed in the pre-specified
sub-group of patients who received prior
treatment with immunotherapy. The median
PFS on the binimetinib arm was 5.5 months
versus 1.6 months on the dacarbazine arm
[HR=0.46 (95% CI 0.26-0.81)]. Confirmed
overall response rate and disease control rate
were 15% (95% CI, 11-20%) and 58% (95% CI,
52-64%) for all patients receiving binimetinib,
respectively, versus 7% (95% CI, 3-13%) and
25% (95% CI, 18-33%) for patients receiving
dacarbazine, respectively. Grade 3/4 adverse
events reported in greater than or equal to
5% of patients receiving binimetinib included
increased creatine phosphokinase and hypertension.
The company plans to submit an
NDA in the next month.
May 16, 2016
SELLAS Life Sciences Group issued results of a phase II trial of WT1 (Galinpepimut-S) cancer vaccine in patients with malignant pleural mesothelioma (MPM). The randomized, double-blind, placebo-controlled trial compared the WT1 analog peptides vaccine in combination with Montanide-adjuvant + Granulocyte-macrophage colony-stimulating factor (GM-CSF) versus Montanide-adjuvant + GM-CSF in patients with MPM who had previously completed combined modality therapy. Thirty-nine patients were to be enrolled in each arm at two centers. The trial showed a median overall survival of 21.4 months for WT1 vaccine-treated patients versus a median 16.6 months overall survival for patients in the placebo control arm. The WT1 cancer vaccine also resulted in a median progression-free survival of 11.4 months, double that of the control arm, 5.7 months, in patients with MPM. The WT1 vaccine demonstrated a favorable safety and tolerability profile in MPM patients. Patients with a complete tumor resection and subsequent treatment with WT1 showed a significant survival benefit. Patients who mounted an immune-response with WT1 had a significant survival benefit. WT1 was very well-tolerated by patients in this trial. Based on these results, SELLAS is preparing to initiate a pivotal phase IIb/III trial of its WT1 vaccine in patients with MPM by the third quarter of 2016.
April 25, 2016
Morphotek reported results of a phase III trial of farletuzumab (MORAb-003) in combination with a platinum standard chemotherapy regimen (carboplatin plus taxane) in platinum-sensitive ovarian cancer patients in first relapse. All subjects received carboplatin plus paclitaxel or docetaxel (for six cycles combined with randomized test product 1:1:1 farletuzumab 1.25mg/kg, farletuzumab 2.5mg/kg, or placebo), and single-agent test product was continued weekly until disease progression. Neither farletuzumab dose met the study’s primary progression-free survival (PFS) endpoint when compared to placebo, with PFS of 9.0, 9.5 (hazard ratio [HR]=0.99) and 9.7 months (HR=0.86) for the placebo, farletuzumab 1.25mg/kg, and farletuzumab 2.5mg/kg arms, respectively. There was no difference in overall survival. Prespecified subgroup analyses demonstrated that subjects with a low CA125 level (less than three times the upper limit of normal) correlated with longer PFS (HR=0.49) and OS (HR=0.44) for farletuzumab 2.5mg/kg versus placebo. Subjects with higher farletuzumab exposure also showed superior PFS and OS compared to placebo. The most common adverse events were those known to be associated with chemotherapy, including alopecia, nausea, neutropenia, fatigue, thrombocytopenia and neuropathy. Morphotek has initiated a phase II trial to investigate the potential clinical benefit observed in patients with a low CA125 level.
April 11, 2016
BioLineRx issued results from BL-8040’s phase II trial in relapsed or refractory acute myeloid leukemia (r/r AML). The trial was a multicenter, open-label study assessing pharmacodynamics and pharmacokinetic parameters of BL-8040 in combination with Cytarabine (Ara-C). Forty-two patients with r/r AML were enrolled in the study (36 of which received a dose of 1mg/kg and higher). The study included a dose escalation stage followed by an expansion stage. Each patient received a once daily dose of BL-8040 monotherapy (from 0.5 to 2mg/kg) on days one to two, followed by the same dose of BL-8040 plus Ara-C on days three to seven. Extensive pharmacodynamic parameters, such as mobilization of leukemic cells and induction of apoptosis, were assessed after monotherapy with BL-8040 using peripheral blood sampling and bone marrow aspirates at baseline and on day three prior to Ara-C administration. Clinical response to treatment was evaluated by bone marrow biopsy on day 30. Results showed BL-8040, as a single agent and in combination with Cytarabine (Ara-C), was safe and well-tolerated at all doses tested up to and including the highest dose level of 2mg/kg, with no major adverse events (n=45). The composite complete remission rate, including both complete remission (CR) and complete remission with incomplete blood count recovery (CRi), was 38% in subjects receiving up to two cycles of BL-8040 treatment at doses of 1mg/kg and higher (n=39). The company plans multiple additional clinical studies for BL-8040. An AML consolidation treatment is currently being investigated in a large phase IIb study at in Germany.
March 28, 2016
Janssen-Cilag International issued phase III results of ZYTIGA (abiraterone acetate) plus prednisone for early and less aggressive chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). COU-AA-302 was an international, randomized, double-blind, placebo-controlled study that included 1,088 men with mCRPC who had not received prior chemotherapy and were randomized to receive ZYTIGA (abiraterone acetate) 1,000 milligrams (mg) administered orally once-daily plus prednisone 5mg administered twice-daily or placebo plus prednisone 5mg administered twice-daily. The co-primary endpoints of the study were rPFS and OS. The post-hoc analysis used the final dataset for the intent-to-treat population (n=1,088), to stratify patients into Group 1 (BPI 0-1, PSA <80 ng/ml and GS <8) and Group 2 (BPI=2 and/or PSA=80ng/ml and/or GS=8). The study provided an 11.8 months overall survival (OS) benefit (53.6 months vs. 41.8 months; HR=0.61 [95% CI, 0.43-0.87]; p=0.0055), compared to an active control of placebo plus prednisone. The post-hoc analysis divided patients into two groups to identify which group experienced a greater treatment benefit. The patients in Group 1 were in an earlier, less advanced and less symptomatic stage of the disease (which was defined as having a Brief Pain Inventory [BPI] Short Form score of 0-1, prostate-specific antigen [PSA] below 80ng/ml and a Gleason score [GS] of below 8). Those in Group 2 were in a later, more advanced and more symptomatic stage of the disease (defined as a having a BPI of 2 or over and/or PSA of 80ng/ml or above, and/or a GS of 8 or more). The analysis revealed that patients in both groups experienced an OS benefit when treated with ZYTIGA plus prednisone, compared to placebo plus prednisone (Group 1: 11.8 months; HR=0.61 [95% CI, 0.43-0.87]; p=0.0055) (Group 2: 2.8 months; HR=0.84 [95% CI, 0.72-0.99]; p=0.0321).
March 21, 2016
Biofrontera issued results of its phase III clinical trial evaluating BF-200 ALA for the treatment of basal cell carcinoma (BCC). Results of the EU-based, multicenter study confirm that 93.4% of patients treated with BF-200 ALA were cleared of all BCCs, compared to only 91.8% of patients treated with the comparator treatment, methyl aminolaevulinate (MAL) photodynamic therapy, which is marketed as Metvix or Metvixia. In the study, 281 patients with one to three non-aggressive BCCs, including both superficial and nodular BCC subgroups, up to a thickness of 2mm were treated. The analysis of the individual BCCs yielded a complete clearance rate of 94.6% after treatment with BF-200 ALA, compared to 92.9% with MAL (all values refer to the per protocol group). A stronger deviation of efficacy between the two drugs became apparent in thicker tumors. While 96.4% of tumors between 0 and 1mm thickness were completely removed by treatment with BF-200 ALA (95.7% MAL), the value decreased in 1 to 2mm tumors to 72.7% with BF-200 ALA and 66.7% with MAL. 89.3% of nodular BCCs, a subgroup of non-aggressive BCCs, were completely cleared with BF-200 ALA in comparison to only 78.6% with MAL. In addition, treatment with BF-200 ALA resulted in an excellent cosmetic outcome. In 60% of patients treated with BF-200 ALA, skin aesthetic appearance was strongly improved and rated by study physicians as very good to excellent, compared to only 48.6 % of patients treated with MAL. To evaluate these characteristics, various skin parameters had been qualified by the study physicians and graded by the severity of skin damage. The improvement of each parameter was documented and included in the analysis. An unsatisfactory result without cosmetic improvement was observed in 17.1% of BF-200 ALA patients and 18.9% of patients treated with MAL.
February 16, 2016
Leap Therapeutics released results of a
four part (Part A, Part B, Part C and Part D),
dose-escalating, open label, multicenter
study evaluating the safety, pharmacokinetics
and efficacy of DKN-01 in combination with
paclitaxel in adult patients with recurrent or
metastatic esophageal or gastro-esophageal
junction cancer with progressive disease
requiring therapy. Nine patients with cancer
of the esophagus or GEJ were enrolled in the
Part A dose escalation; all were evaluable per
the protocol. Patients received either 150mg
or 300mg twice monthly in combination with
weekly infusions of 80mg/m2 paclitaxel. The
combination of DKN-01 and paclitaxel was
safe and well-tolerated at all doses. There were
no treatment related severe adverse events
(SAEs), or treatment emergent adverse events
(TEAE) leading to study discontinuation.
Three patients had PRs and four patients had
best responses of Stable Disease, with a total
disease control rate of 77.7%. Treatment with
300mg of DKN-01 twice monthly was selected
for further study in combination with weekly
infusions of 80mg/m2 paclitaxel. Patients with
adenocarcinoma of the esophagus or GEJ with
fewer lines of therapy may derive greater benefit
(n=4, ORR=75%, median PFS=37.3 weeks).
February 8, 2016
OncoGenex Pharmaceuticals reported results of a phase II trial evaluating the combination of apatorsen with carboplatin and pemetrexed in patients with untreated metastatic non-small cell lung cancer (NSCLC). Data did not reach the statistical significance required to demonstrate a progression-free survival (PFS) benefit. The placebo-controlled, double-blind, randomized trial enrolled 155 subjects. A potential PFS benefit was observed in patients with high baseline serum Hsp27 status when treated with apatorsen. The study is ongoing and overall survival results are expected in the second half of 2016. Treatment and maintenance therapy with apatorsen was well-tolerated. Adverse events were comparable between the arms and as expected for the study chemotherapy treatment.
February 1, 2016
Leap Therapeutics, a biotechnology company developing novel therapeutics at the leading edge of cancer research, reported its first results of a clinical trial of its lead candidate DKN-01, a monoclonal antibody against the Dickkopf-1 (DKK1) protein. Data from the trial demonstrated meaningful clinical activity in relapsed or refractory cancer of the esophagus or gastro-esophageal junction (GEJ), indications with limited approved therapies. In Part A of the study, the dose escalation phase, three of nine patients achieved a partial response (PR) per RECIST v1.1. In the subset of patients with adenocarcinoma who had received one or two prior lines of therapy, three of four patients achieved a PR. “Patients with relapsed or refractory esophageal carcinoma have an extremely poor prognosis,” commented David Ryan, M.D. Massachusetts General Hospital. “The results from the study of DKN-01 in combination with paclitaxel, while early, provide great encouragement, and we look forward to the data from the next phases of this trial.”
January 25, 2016
Merrimack Pharmaceuticals issued results of a phase III study of ONIVYDE (irinotecan liposome injection) in combination with fluorouracil (5-FU) and leucovorin achieved a substantial improvement in 12-month overall survival in patients with post-gemcitabine metastatic pancreatic adenocarcinoma when compared to 5-FU and leucovorin alone. The randomized, open label study in patients with metastatic adenocarcinoma of the pancreas who received prior gemcitabine-based therapy was the largest phase III study in this setting to date. A total of 417 patients were randomized across the three arms. Primary survival analysis was based on 313 events and showed that ONIVYDE in combination with 5-FU and leucovorin significantly improved overall survival v. 5-FU and leucovorin alone: 6.1 months v. 4.2 months (p=0.012, unstratified hazard ratio (HR) =0.67, 95% CI: [0.49-0.92]). The monotherapy regimen in this study did not show improvement over the 5-FU and leucovorin arm: 4.9 v. 4.2 months (p=0.94, HR=0.99, 95% CI: [0.77-1.28]). No new safety or tolerability concerns were note in the updated analysis. The primary NAPOLI-1 study results were the basis of the recent FDA and Taiwan FDA approval of ONIVYDE in combination with 5-FU and leucovorin for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy. Merrimack and Baxalta have entered into an exclusive licensing agreement for the development and commercialization of ONIVYDE outside of the U.S. and Taiwan. Baxalta’s marketing authorization application for the treatment of patients with metastatic adenocarcinoma of the pancreas who have been previously treated with gemcitabine-based therapy is currently under review with the EMA.
Novocure issued results of a phase II trial showing Tumor Treating Fields (TTFields) therapy plus first-line chemotherapy gemcitabine is tolerable and safe in patients with advanced pancreatic cancer. The first cohort of the prospective, single-arm study included 20 patients with advanced pancreatic cancer whose tumors could not be removed surgically and who had not received chemotherapy or radiation therapy prior to the clinical trial. The primary endpoint measured the incidence and severity of treatment-related adverse events. As a result of TTFields therapy, 10 patients experienced treatable contact dermatitis. No serious adverse events related to TTFields were reported. Fourteen patients reported serious adverse events unrelated to TTFields therapy. In relation to these reported results for gemcitabine alone, PANOVA patients who received TTFields therapy plus first-line gemcitabine experienced a median progression free survival of 8.3 months compared to 3.7 months, a median overall survival of 14.9 months compared to 6.7 months and a median one-year survival of 55% compared to 22%. Thirty percent of the evaluable tumors had partial responses compared to 7% with gemcitabine alone and another 30% had stable disease. The PANOVA trial includes a second cohort testing TTFields plus gemcitabine and nab-paclitaxel in an additional 20 patients. Based on these data, the company will accelerate planning of a phase III clinical trial in pancreatic cancer.
Sellas Life Sciences Group reported positive results from a phase I/II clinical study of the WT1 cancer vaccine in patients with multiple myeloma (MM) following autologous stem cell transplantation. Sellas’s trial enrolled 15 patients, each patient receiving chemotherapy and stem cell transplantation and followed by one to two cycles (six vaccines per cycle) of the company’s WT1 cancer vaccine. Of the patients enrolled, 60% were found to have high risk cytogenetics at diagnosis (9/15), including del p53; this is the most difficult population to maintain in long-lasting remission. Initial data have shown positive safety findings and that treatment with the WT1 vaccine was well-tolerated. Initial results from the study have demonstrated positive immune response data and safety findings as well as early efficacy data. Three patients with high-risk cytogenetics achieved an immune response against WT1 peptides encoded in the vaccine, and two of these patients continued in remission at the time of last follow-up at one year; the third patient was in remission as of the first, three-month follow-up and will continue to be followed through one year. Sellas intends to assess the efficacy of the WT1 cancer vaccine in MM in a larger phase II/III trial including patients with standard risk disease following induction chemotherapy in 2016.
January 18, 2016
Astellas US and Medivation released
results from the phase II TERRAIN trial of
enzalutamide compared to bicalutamide in
metastatic castration-resistant prostate cancer
(CRPC). The trial enrolled 375 patients in North
America and Europe, and evaluated enzalutamide
160mg once daily versus bicalutamide
50mg once daily. The TERRAIN study achieved
its primary endpoint demonstrating a statistically
significant increase in progression-free
survival (PFS) for enzalutamide compared to
bicalutamide (hazard ratio=0.44; 95% confidence
interval, 0.34-0.57; p<0.0001). Median
PFS, defined as time from randomization to
centrally confirmed radiographic progression,
skeletal-related event, initiation of new
anti-neoplastic therapy or death, whichever
occurred first, was 15.7 months in the enzalutamide
group compared to 5.8 months in the
bicalutamide group. The observed adverse
event profile of enzalutamide in TERRAIN
appeared consistent with that from phase
III enzalutamide trials. The median time on
treatment in TERRAIN was 11.7 months in the
enzalutamide group versus 5.8 months in the
bicalutamide group. Serious adverse events
were reported in 31.1% of enzalutamide-treated
patients and 23% of bicalutamide-treated
patients. Individual grade three or
higher adverse events largely occurred at a
similar rate (<1% difference) between treatment
groups, with the exception of hypertension
(7.1% v. 4.2%) and back pain (2.7% v.
1.6%), which occurred more frequently in the
enzalutamide treatment group. Grade three or
higher cardiac events were reported in 5.5%
of enzalutamide-treated patients versus 2.1%
of bicalutamide-treated patients. Two seizures
were reported in the enzalutamide group and
one in the bicalutamide group.
Genentech reported results of a phase II
study of venetoclax for chronic lymphocytic
leukemia (CLL). The study met its primary
endpoint, with an overall response rate (ORR)
of 79.4% with venetoclax, as assessed by
an independent review committee (IRC). In
addition, 7.5% of people achieved a complete
response with or without complete
recovery (complete response without normal
blood counts) in the bone marrow. Forty-five
people had an assessment for minimal
residual disease (MRD) in the blood. Notably
18 people (17% of the total, 21% of responders)
achieved MRD-negativity, meaning no
cancer could be detected using a specific test.
Ten of these 18 people also had bone marrow
assessments and six were MRD-negative. At
one year, 84.7% of all responses and 94.4% of
MRD-negative responses were maintained.
The one-year progression-free survival (PFS)
and overall survival (OS) rates were 72% and
86.7%, respectively. No unexpected safety
signals were reported. AbbVie has submitted
an NDA for venetoclax to the FDA. Venetoclax
received Breakthrough Therapy designation
from the FDA earlier this year for the treatment
of people with relapsed or refractory
CLL harboring the 17p deletion. AbbVie also
has submitted a marketing authorization
application (MAA) to the EMA. Submissions to
other regulatory authorities around the world
are planned in 2016.
Sorrento Therapeutics reported results
of a phase III study of STI-001 in China for
epidermal growth factor receptor (EGFR)
expressing metastatic colorectal carcinoma
patients. STI-001 was used in combination
with irinotecan versus irinotecan alone. The
combination therapy showed significant
improvement compared to chemotherapy
alone in overall response rate (ORR: 32.9% v.
12.8%) and progress-free survival (PFS: 5.6 v.
3.2 months) as well as longer overall survival
(OS: 14.1 v. 13.4 months). The ORR, PFS and
OS using STI-001 and irinotecan are increased
significantly than previously reported in
similar medical settings using Erbitux and
irinotecan (32.9% v. 10%; 5.6 v. 4 months;
14.1 v. 11.6 months). During the 501-patient,
double-blind, randomized trial, STI-001 was
well-tolerated. Adverse events (AEs), especially
grade three and four AEs, were found to
be significantly fewer than those previously
reported using Erbitux. While it was reported
that more than 10% of patients using Erbitux
showed hypersensitive reaction (grade three/
four), none was recorded in the completed
phase III study of STI-001.
January 11, 2016
Exelixis has issued results of a phase III trial comparing cabozantinib to everolimus in 658 patients with renal cell carcinoma (RCC). The trial met its primary endpoint of demonstrating a statistically significant increase in PFS for cabozantinib as compared to everolimus, as determined by an independent radiology committee. Per the trial protocol, the primary analysis was conducted among the first 375 patients randomized to ensure sufficient follow-up and a PFS profile that would not be primarily weighted toward early events. The median PFS for that population was 7.4 months for the cabozantinib arm v. 3.8 months for the everolimus arm, corresponding to a 42% reduction in the rate of disease progression or death for cabozantinib as compared to everolimus (hazard ratio [HR]=0.58, 95% confidence interval [CI] 0.45-0.75, p<0.001). As assessed by an independent radiology committee, the median PFS across all enrolled patients was 7.4 months for the cabozantinib arm v. 3.9 months for the everolimus arm, corresponding to a 48% reduction in the rate of disease progression or death for cabozantinib as compared to everolimus (HR = 0.52, 95% CI 0.43-0.64, p<0.001). Cabozantinib currently is marketed in capsule form under the brand name Cometriq in the U.S. for the treatment of progressive, metastatic medullary thyroid cancer (MTC), and in the E.U. for the treatment of adult patients with progressive, unresectable locally advanced or metastatic MTC.
December 21, 2015
Spectrum Pharmaceuticals has reported results of a phase I combination trial of belinostat (Beleodaq) with the CHOP (cyclophosphamide, hydroxyl-doxorubicin, Oncovin and Prednisone) chemotherapy regimen as first-line treatment for newly diagnosed peripheral T-cell lymphoma (PTCL). Oncovin is a brand name for vincristine. The open-label, two-part trial enrolled a total of 23 patients. Eleven were enrolled in part A, the dose-escalation phase, to determine the study’s primary endpoint, the maximum tolerated dose (MTD). Part B of the study, the expansion phase, enrolled 12 additional patients at that dose level. The MTD of belinostat was established at 1,000mg/m2 IV infusion on days one through five (the recommended single agent dose) when combined with the CHOP regimen, with each component given at its full recommended dose. Secondary endpoints included safety, tolerability, Objective Response Rate (ORR: complete response + partial response) and pharmacokinetics. Results showed an ORR of 86% with the belinostat and CHOP combination, based on 21 evaluable patients (18/21), with the vast majority, 67%, achieving a complete response (14/21), and 19% achieving a partial response (4/21). In addition, the belinostat and CHOP combination was shown to have an acceptable safety profile with no new or unexpected toxicities. The most common (>10%) grade three/four hematologic adverse events (AEs) reported with Bel-CHOP were as expected: neutrophil count decreased (30%), anemia (22%), neutropenia (22%), white blood cell (WBC) count decreased (22%), febrile neutropenia (17%) and lymphocyte count decreased (17%). No grade three/four non-hematologic AEs >10% were reported. No patient discontinued therapy due to AEs. One patient died as a result of disease progression during the study. Beleodaq is a histone deacetylase (HDAC) inhibitor that received accelerated approval by the FDA for the treatment of relapsed or refractory PTCL in July 2014.
December 14, 2015
Takeda Pharmaceutical has reported results of a phase III trial of NINLARO (ixazomib) for relapsed and/or refractory multiple myeloma. The TOURMALINE-MM1 trial is an international, randomized, double-blind, placebo-controlled trial designed to evaluate once-weekly oral ixazomib plus lenalidomide and dexamethasone compared to placebo plus lenalidomide and dexamethasone. Trial results demonstrate a statistically significant (35%) improvement in progression free survival (PFS), with patients treated in the ixazomib arm living for a significantly longer time without their disease worsening compared to patients in the control arm (20.6 months vs. 14.7 months in control group; Hazard Ratio [HR] 0.742; p = 0.012). Overall response rate (ORR) was 78.3% in the ixazomib arm and median duration of response was 20.5 months, v. 71.5% and 15 months in the control group. Median PFS in high-risk patients (HR 0.543; HR 0.596 in patients with del(17p)) was similar to that in the overall patient population and in standard-risk patients. The most common grade three adverse events included neutropenia, anemia, thrombocytopenia and pneumonia. Gastrointestinal events included diarrhea, nausea, and vomiting. Peripheral neuropathy rates were 28% in the IRd arm v. 21% in the control arm, 35% v. 21% had rash events, 8% v. 10% had acute renal failure, and 4% v. 3% had heart failure. NINLARO was recently approved by the FDA in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.
December 7, 2015
Exelixis has issued results of a phase III
trial of Cotellic (cobimetinib) in patients
with previously untreated resectable, locally
advanced or metastatic melanoma carrying a
BRAF V600E or V600K mutation, in combination
with vemurafenib. In October, Exelixis
announced the coBRIM trial met its OS secondary
endpoint, demonstrating a statistically
significant increase in OS for the combination
of Cotellic and vemurafenib compared to vemurafenib
monotherapy. The median OS was
22.3 months for the combination of Cotellic
and vemurafenib v. 17.4 months for vemurafenib
alone, corresponding to a 30% reduction
in the rate of death for the combination
as compared to vemurafenib alone (hazard
ratio [HR]=0.70, 95% confidence interval [CI]
0.55-0.90, p=0.005). Ongoing study monitoring
did not identify any new safety signals. On
Nov. 10, the FDA approved Cotellic as a treatment
for patients with BRAF V600E or V600K
mutation-positive unresectable or metastatic
melanoma, in combination with vemurafenib.
Cotellic was first approved in Switzerland in
late August. The Cotellic approvals are based
on data from coBRIM, the phase III pivotal trial
conducted by Genentech in 495 patients with
previously untreated unresectable, locally
advanced or metastatic melanoma carrying a
BRAF V600 mutation. Genentech sponsored
the U.S. NDA and Roche sponsored the Swiss
regulatory application. Roche also filed a
Marketing Authorization Application (MAA)
with the EMA in late 2014, and the Committee
for Medicinal Products for Human Use issued
a positive recommendation on the MAA in
September of this year. Roche anticipates a
decision from the European Commission by
Merrimack and Baxalta have reported
results of a global, randomized, open-label
phase III trial of Onivyde, in combination
with 5-FU and leucovorin, for treatment of
metastatic adenocarcinoma of the pancreas.
Patients were enrolled at 76 sites in North
America, South America, Europe, Asia and
Oceania. A total of 417 patients were randomized
across the three arms. The Onivyde combination
regimen demonstrated a significant
increase in median overall survival v. 5-FU and
leucovorin alone: 6.1 months v. 4.2 months
(p=0.012, unstratified hazard ratio for death
(HR) =0.67, 95% CI: [0.490.92]). The monotherapy
regimen in the study did not show
improvement over the 5-FU and leucovorin
arm: 4.9 v. 4.2 months (p=0.94, HR=0.99, 95%
CI: [0.771.28]). Onivyde in combination with
5-FU and leucovorin achieved a longer progression-
free survival compared with the 5-FU
and leucovorin arm (3.1 months v. 1.5 months;
unstratified HR=0.56 [95% CI, 0.410.75]). Unconfirmed
objective response rate was higher
in the Onivyde in combination with 5-FU and
leucovorin arm than in the 5-FU and leucovorin
arm: 16% (19/117) v. 1% (1/119) (difference
15.4 percentage points, 95% CI, 8.5-22.3;
p<0.0001). The most common grade three
or four adverse events that occurred more
frequently in the Onivyde combination arm
(>2% incidence v. 5-FU and leucovorin) were
neutropenia, diarrhea, vomiting and fatigue.
Study results were the basis of the recent FDA
and Taiwan FDA approval. In May 2015, the
EMA accepted for review Baxalta’s marketing
authorization application for Onivyde based
on the same clinical results.
November 16, 2015
Merck has reported results of a randomized,
pivotal phase II/III study comparing
two doses of Keytruda (the FDA-approved
2mg/kg dose and a higher, investigational
10mg/kg dose, each given every three
weeks) to docetaxel, a commonly used
chemotherapy, for advanced non-small-cell
lung cancer (NSCLC). KEYNOTE-010 is a
global, open-label study in 1,034 patients.
A topline analysis revealed that treatment
with Keytruda was associated with longer
overall survival (OS) compared with
docetaxel treatment. That result was true for
both the approved and the investigational
dose of Keytruda, which showed similar
efficacy. It was also true in both the first set
of patients analyzed—those with a tumor
proportion scores (TPS) of 50% or greater
and for all enrolled patients, all of whom
had a TPS of 1% or greater. Treatment with
Keytruda, at both doses, also provided
superior progression-free survival (PFS) v.
that achieved following treatment with
docetaxel in patients whose tumors had
TPS values equal to or greater than 50%. For
PFS, Keytruda treatment was numerically
but not statistically superior to docetaxel in
the all PD-L1 positive group, again at both
doses. The safety profile of Keytruda in that
trial was consistent with that observed in
previously reported studies in patients with
November 2, 2015
Immunomedics has reported results of
a phase III trial of sacituzumab govitecan
for metastatic triple-negative breast (TNBC),
small-cell (SCLC) and non-small-cell lung
(NSCLC) cancers. At the time of analysis, 56
enrolled patients had received sacituzumab
govitecan at the optimal dose of 10mg/kg
given on days one and eight of a three-week
cycle. Treatment response was available for
52 patients. The objective response rate was
29% (15/52), with two confirmed complete
responses. The interim median progression-free
survival (PFS), a measure of time patients
are living without their cancer progressing,
was seven months. Forty-six percent of these
TNBC patients had experienced a PFS event.
Overall survival (OS) data were too early to
report because 86% of patients are still alive.
For metastatic lung cancers, 33 patients with
NSCLC were enrolled to receive sacituzumab
govitecan at the 8.mg/kg or 10mg/kg dose
level. Among 29 patients assessable, an
objective response rate of 28% (8/29) was
observed, including patients with both squamous
cell and adenocarcinoma NSCLC types.
For the 25 patients at the 10mg/kg dose, the
interim median PFS was 3.8 months, with
48% of patients in this dose group having
experienced a PFS event. In SCLC, of the 27
patients enrolled at doses of 8mg/kg and
10mg/kg, 25 were assessable for response.
Six patients achieved a partial response (objective
response rate=24%). Interim median
PFS for the 12 patients at the 10mg/kg dose
level was 3.6 months and 83% of patients
had experienced a PFS event. Since 96% of
NSCLC patients and 100% of SCLC patients
were still alive at the time of analysis, OS
data at the optimal dose of 10mg/kg are too
early to report. Sacituzumab govitecan has
received Fast Track designation from the FDA
for the treatment of patients with TNBC, SCLC
and NSCLC, and also has been designated an
orphan drug for SCLC or pancreatic cancer
in the U.S., and for the treatment of patients
with pancreatic cancer in the E.U.
October 26, 2015
BeyondSpring Pharmaceuticals has
released results of a phase III study of Plinabulin
combined with docetaxel for non-small cell lung
cancer (NSCLC) in patients who have lung lesions
greater than 3cm. Patients were randomized
one-to-one in a Plinabulin plus docetaxel treatment
arm compared to docetaxel alone. Patients
in the treatment arm received 30mg/m2 dose
of Plinabulin, which was selected as the dose for
an ongoing phase III study. Analysis of median
overall survival (OS) according to tumor size of
any lesion demonstrated evident OS benefit in
favor of Plinabulin and docetaxel treatment arm,
as shown by hazard ratio (HR). In patients with
lesions greater than 3 cm, HR gradually decreased
to <0.6. The HR range was 0.97-0.50. That
trend was consistently observed independent
of number of prior treatments. The importance
of location of lesions also was analyzed. It was
apparent that patients with advanced lesions in
lung parenchyma received more benefit from
Plinabulin plus docetaxel treatment (HR=0.76)
regardless of lesion size. The HR range (0.84-0.44)
based on lung lesion size also was consistent
with findings based on size of all lesion including
extra-pulmonary lesions. Treatment with
Plinabulin plus docetaxel was well-tolerated, with
most common adverse events consistent with
chemotherapy side effects and including nausea,
fatigue, diarrhea, constipation, anorexia, fever,
vomiting and transient blood pressure elevation,
which were mostly grade 1-2.
October 19, 2015
OncoSec Medical has issued results of
a phase II trial of ImmunoPulse IL-12 for
merkel cell carcinoma (MCC). OMS-I110 was
an open-label study that enrolled 15 patients
with MCC. In the study, 79% of patients
(11/14) showed an increase in IL-12 protein
levels in tumor biopsy samples obtained
about 22 days after treatment compared to
baseline, indicating that ImmunoPulse IL-12
leads to successful DNA transfection and
sustained protein expression within the tumor
microenvironment. ImmunoPulse IL-12 was
well-tolerated, with no treatment-related
adverse events above grade two and no
treatment-related serious adverse events. The
most common adverse event was grade one
transient pain associated with the treatment
procedure. Analysis of individual lesions found
that 30% of patients (3/10) who were evaluable
for systemic anti-tumor immunity had
regression of at least one distant, non-injected/
non-electroporated lesion. In patients
considered evaluable for objective response
by modified RECIST criteria (i.e., cohort B,
N=12), 25% of patients (3/12) had an objective
partial response (PR) and one patient had
stable disease (SD) for a disease control rate
(PR + SD) of 33%. In cohort A (N=3), one patient
had a pathologic complete response and
continues to be recurrence-free at six months.
Another patient has been recurrence-free for
over three years.
October 5, 2015
Boehringer Ingelheim has released results
of a phase III trial of fatinib compared
to erlotinib for the treatment of patients
with previously treated advanced squamous
cell carcinomas (SCC) of the lung. More patients
had improved overall health-related
quality-of-life (36% v. 28%, p=0·041), cough
(43% v. 35%, p=0·029) and dyspnoea (51%
v. 44%, p=0·061) with afatinib than with
erlotinib. The rate of severe adverse events
in the LUX-Lung 8 trial was similar between
the two treatment arms with differences
observed in the incidence of certain side effects.
A higher incidence of severe diarrhoea
and stomatitis (mouth sores) was observed
with afatinib compared to erlotinib (grade
3 diarrhoea: 10% v. 2%; grade 3 stomatitis:
4% v. 0%), while a higher incidence of
severe rash/acne was reported with erlotinib
compared to afatinib (grade 3 rash/acne:
10% v. 6%). Diarrhoea occurring in patients
treated with afatinib was manageable. Afatinib
is under review by both the FDA and
EMA for the treatment of SCC of the lung.
Afatinib also has been granted Orphan Drug
designation by the FDA. Afatinib currently
is approved in more than 60 countries for
the first-line treatment of specific types of
EGFR mutation-positive non-small cell lung
Exelixis has issued results of a phase III
trial comparing cabozantinib to everolimus
in 658 patients with renal cell carcinoma
who have experienced disease progression
following treatment with a VEGF receptor tyrosine
kinase inhibitor. The median PFS was
7.4 months for the cabozantinib arm v. 3.8
months for the everolimus arm, corresponding
to a 42% reduction in the rate of disease
progression or death for cabozantinib as
compared to the everolimus arm (hazard
ratio [HR]=0.58, 95% confidence interval [CI]
0.45-0.75, p<0.001). The company is on track
to complete an NDA filing with the FDA by
the end of 2015. Cabozantinib has received
Breakthrough Therapy designation in the
U.S. and Exelixis expects a European filing to
follow in early 2016.
September 8, 2015
Janssen R&D has released results from a
multicenter, two-part, open-label, phase I/II
study of daratumumab for relapsed or refractory
multiple myeloma. In part 1, 32 patients
were treated with escalating doses and no
maximum tolerated dose was identified. In
part 2, 72 patients were enrolled in a dose
expansion cohort and received either
8mg/kg (30 patients) or 16mg/kg (42 patients)
of daratumumab at various schedules until
disease progression or unmanageable toxicity
to optimize doses identified in part 1. Following
that study, 16 mg/kg was chosen as the
dose to be used in all daratumumab clinical
trials. Patients had a median of four prior lines
of therapy and 79% were refractory to their
last therapy, including both lenalidomide
and bortezomib (64%). Additionally, 76% of
patients previously received an autologous
stem cell transplant. In the 16mg/kg cohort,
the ORR was 36% (11 partial responses, two
very good partial responses and two complete
responses) and 10% in the 8mg/kg cohort
(three partial responses). The two complete
responses were confirmed with the use of a
novel assay. Median progression-free survival
was 5.6 months (95% CI: 4.2, 8.1) and 65%
(95% CI: 28, 86) of responders remained in
remission at 12 months. In the 16mg/kg
cohort, serious adverse events (AEs) occurred
in 33% of patients. Infusion-related reactions
(IRRs) occurred in 71% of patients in both the
8mg/kg and 16mg/kg cohorts, and all were
grades 1 and 2, except for the occurrence of
grade 3 reactions in one patient. The majority
of IRRs occurred during the first infusion, with
notably fewer during subsequent infusions.
No patient discontinued treatment due to an
IRR. The most common AEs in either treatment
group were fatigue, allergic rhinitis and pyrexia
(fever). On July 9, Janssen completed the
rolling submission of its BLA for daratumumab
to the FDA for the treatment of patients with
multiple myeloma who have received at least
three prior lines of therapy, including a PI and
an IMiD, or who are double refractory to a proteasome
inhibitor and an immunomodulatory
agent. Daratumumab received Breakthrough
Therapy designation from the FDA for this
patient population in May 2013.
August 10, 2015
Lexicon Pharmaceuticals reported results
of a phase III study of telotristat etiprate for
carcinoid syndrome patients with metastatic
neuroendocrine tumors (NET). The double-blind
study enrolled 135 patients and evaluated
two doses of oral telotristat etiprate—
250mg and 500mg, each taken three times
daily—against placebo over a 12-week period.
Top-line results show that patients who added
telotristat etiprate to SSA therapy at both
the 250mg and 500mg doses experienced a
statistically significant reduction from baseline
compared to placebo in the average number
of daily bowel movements over the 12-week
study period (p<0.001), meeting the study’s
primary endpoint. In another key finding, a
substantially greater proportion of patients on
telotristat etiprate achieved a durable response
(44% and 42% in the 250mg and 500mg arms,
respectively), defined as at least a 30% reduction
in daily bowel movements over at least
half the days of the study period, as compared
to 20% response on placebo (p<0.040). The
12-week double-blind study period is being
followed by a 36-week open-label extension
where all patients receive telotristat etiprate
500mg three times daily.
July 13, 2015
Novartis issued results of a phase III
study of with the combination of Tafinlar
(dabrafenib) and Mekinist (trametinib)
compared to Tafinlar monotherapy alone
for BRAF V600E/K mutation-positive
metastatic melanoma. COMBI-d is a pivotal,
phase III, randomized, double-blinded
study in patients with unresectable (stage
IIIC) or metastatic (stage IV) BRAF V600E/K
mutation-positive cutaneous melanoma.
The study randomized 423 patients. The final
OS analysis showed that the combination of
Tafinlar and Mekinist achieved a statistically
significant OS benefit compared to Tafinlar
monotherapy (median of 25.1 months v.
18.7 months; Hazard Ratio [HR] 0.71 [95%
Confidence Interval (CI), 0.55-0.92], p=0.011).
A 33% reduction in the risk of progression or
death was demonstrated with the combination
therapy compared to monotherapy (median
PFS of 11 months in the 211 patients receiving
combination therapy v. 8.8 months in
the 212 patients receiving monotherapy; HR
0.67 [95% CI, 0.53-0.84], p<0.001). The combination
achieved ORR of 69% compared to
53% for monotherapy [difference=15% (95%
CI, 6.0%-24.5%), p=0.001]. The median DoR
for the 144 responders receiving combination
therapy was 12.9 months [95% CI,
9.4-19.5] compared to 10.6 months in the
113 responders receiving monotherapy [95%
CI, 9.1-13.8]. The safety results were consistent
with the profile observed to date for the
combination and consistent with the profile
observed for Tafinlar monotherapy; no new
safety concerns were observed. Completion
of COMBI-d is a post-marketing requirement
for the FDA’s accelerated approval for the
combination in the U.S.
June 29, 2015
Genentech released results of a phase II study
of Perjeta (pertuzumab) in combination with
Herceptin (trastuzumab) and docetaxel
chemotherapy for HER2-positive early breast
cancer (eBC). The randomized, multicenter,
international study enrolled 417 people with
newly diagnosed HER2-positive, operable, locally
advanced or inflammatory eBC. Participants
were randomized to one of four study arms
and received four cycles (12 weeks) of neoadjuvant
treatment followed by surgery and a
year of adjuvant treatment with Herceptin plus
chemotherapy. Both progression-free survival
(PFS) and disease-free survival (DFS) were evaluated
at three years. The results suggested that
people who received the Perjeta regimen prior
to surgery were 31% less likely to experience
disease worsening, recurrence or death (PFS
HR=0.69; 95% CI, 0.34–1.40) compared to those
who received Herceptin and chemotherapy.
People treated with the Perjeta regimen also
were 40% less likely to experience disease recurrence
or death (DFS HR=0.60; 95% CI, 0.28–1.27).
The results suggested that people who achieved
pathological complete response (pCR; no tumor
tissue detectable at the time of surgery in the affected
breast and local lymph nodes) were more
likely across all arms of the study to be alive and
disease-free at three years (PFS HR=0.54; 95% CI,
0.29–1.00; DFS HR=0.68; 95% CI, 0.36–1.26). It
previously was reported that the Perjeta regimen
significantly increased the number of people
who achieved pCR compared to Herceptin and
docetaxel chemotherapy (39.3% v. 21.5%). In
2013, the FDA granted accelerated approval of
the Perjeta regimen for neoadjuvant treatment
in people with high-risk, HER2-positive eBC.
Roche recently submitted a MAA to the EMA for
the Perjeta regimen as a neoadjuvant treatment
for people with HER2-positive eBC.
June 22, 2015
OncoGenex Pharmaceuticals released results of a phase III study of custirsen therapy in men with metastatic castrate-resistant prostate cancer (CRPC) who had a poor prognosis. The trial evaluated custirsen plus docetaxel/prednisone compared with docetaxel/prednisone alone in men with metastatic CRPC (n=1,022). Following 509 deaths, median overall survival (OS) was 23.4 months (m) v. 22.2 m for custirsen and control arms, respectively (hazard ratio [HR] 0.93; P = 0.42). Median survival for the poor and good prognosis groups in the control arm was 14 m and 30.4 m, respectively (HR = 3.66). The custirsen HR effect differed between poor and good prognosis groups (interaction P = 0.069). The HR estimate for custirsen survival benefit for those in the poor prognosis group was 0.73 (95% CI: 0.59 to 0.90) and 1.02 (95% CI: 0.76 to 1.37) for those in the good prognosis. When analyzed separately (n=492), the median OS in the poor prognostic group was 17 m in the custirsen arm v. 14 m in the control arm (HR=0.73, 95% CI: 0.59 to 0.90, P = 0.004).
June 15, 2015
Janssen R&D reported results of a phase III study of trabectedin (Yondelis) compared to dacarbazine for advanced liposarcoma (LPS) or leiomyosarcoma (LMS) previously treated with an anthracycline and at least one additional chemotherapy regimen. Both treatments were administered via an IV infusion every three weeks with the trabectedin dose of 1.5mg/m2 given over 24 hours v. dacarbazine dose of 1g/m2 given over 20-120 minutes. In this randomized, active-controlled study in patients with advanced LPS or LMS, trabectedin significantly reduced the risk of disease progression or death by 45% compared with those who received dacarbazine (hazard ratio [HR] = 0.550; P<0.0001; median [M] 4.2 v. 1.5 months, respectively), with results validated through an audit by independent radiologists. Safety findings were consistent with the well-characterized safety profiles of both agents, with the most common grade 3-4 toxicities in the trabectedin v. the dacarbazine groups being decreased absolute neutrophil count (40% v. 25%), decreased platelets (19% v. 20%) and transient increases in liver transaminases, including alanine transaminase (29% v. 1%). Drug-related deaths occurred in 2.1% of patients in the trabectedin group v. 0% of patients in the dacarbazine group. Trabectedin is approved in 77 countries in North America, Europe, South America and Asia for the treatment of advanced STS as a single agent. Janssen submitted an NDA to the FDA on November 24, 2014, which was granted Priority Review on February 3, 2015.
March 30, 2015
Astellas Pharma and Medivation issued
results from a phase II study of enzalutamide
compared to bicalutamide in metastatic
castration-resistant prostate cancer (CRPC).
The phase II trial enrolled 375 patients in North
America and Europe and was designed to
evaluate enzalutamide at a dose of 160mg
taken orally once daily v. bicalutamide at a dose
of 50mg taken once daily. The median PFS in
the enzalutamide arm was 9.9 months longer
compared to that in the bicalutamide arm
(15.7 v. 5.8 months, respectively) with a Hazard
Ratio (HR) of 0.44 (95% confidence interval
[CI], 0.34-0.57; p<0.0001). The median time to
PSA progression was 13.6 months longer with
enzalutamide (19.4 months) relative to bicalutamide
treatment (5.8 months) with an HR of
0.28 (p<0.0001). 82% of enzalutamide-treated
patients achieved >= 50% PSA reduction from
baseline by week 13 v. 21% of bicalutamide-treated
patients. The median time on enzalutamide
treatment was 11.7 months compared
to 5.8 months on bicalutamide.
March 2, 2015
Immunomedics reported results of a study
of sacituzumab govitecan for treatment of
non-small cell lung cancer (NSCLC) and small
cell lung cancer (SCLC). A total of 44 heavily-pretreated
patients with relapsed or refractory
lung cancer have been enrolled into this
multicenter study. At the time of analysis, 16
patients with SCLC and 18 with NSCLC were
evaluated by computed tomography for response
and time-to-progression (TTP). Despite
the late-stage setting, TTP for most patients
was longer with sacituzumab govitecan than
the duration of their previous lung cancer therapy.
33% of patients with SCLC and 31% with
NSCLC had their tumor reduced in size by 30%
or more. Sacituzumab govitecan controlled
the progression of the cancer in 75% and
56% of NSCLC and SCLC patients, respectively.
These patients had either failed to respond to
their last lung cancer therapies or their cancer
had returned or progressed. Sacituzumab
govitecan continues to produce an acceptable
safety profile in heavily-pretreated patients,
with neutropenia (24% grades three and four
combined) as the major toxicity. Diarrhea, the
typical side effect of irinotecan treatment, was
minimal at 3% grade three. More importantly,
repeated efficacious doses of the ADC can be
given to patients over months without evoking
any interfering immune response.
February 16, 2015
GlaxoSmithKline released results of a phase
III comparison study of the BRAF inhibitor,
dabrafenib, and the MEK inhibitor, trametinib,
to single-agent therapy with dabrafenib and
placebo in patients with unresectable (stage
IIIC) or metastatic (stage IV) BRAF V600E/K
mutation-positive cutaneous melanoma. The
pivotal, phase III, randomized, double-blinded
study enrolled 423 patients from investigative
sites in Australia, Europe and North and South
America. Overall survival results demonstrate
a statistically significant reduction in the risk of
death (Hazard Ratio [HR] 0.71 [95% Confidence
Interval (CI): 0.55, 0.92], p=0.011) for
the combination of dabrafenib (Tafinlar) and
trametinib (Mekinist) compared to dabrafenib
monotherapy in patients with BRAF V600E/K
mutation-positive metastatic melanoma. The
safety profile was consistent with the profile
observed to date for the combination; no new
safety concerns were observed. At the time of
the primary analysis, the most common adverse
events (=20%) for the combination arm
were pyrexia, fatigue, headache, nausea, chills,
joint pain (athralgia), diarrhoea, rash, hypertension
and vomiting. More patients had AEs leading
to dose modifications with combination
arm compared to dabrafenib monotherapy.
Increased incidence (51% v. 28%) and severity
(grade 3, 6% v. 2%) of pyrexia occurred with
combination. Increased incidence of hyperkeratosis
(32% v. 3%) occurred with dabrafenib
monotherapy. Completion of this study is a
post-marketing requirement for the FDA’s
Accelerated Approval for the combination in
the U.S. The final data from COMBI-d will be
submitted in the coming months.
February 9, 2015
Boehringer Ingelheim released results
of two phase III trials of afatinib compared
to standard chemotherapy for epidermal
growth factor receptor (EGFR) mutation-positive
patients with metastatic non-small
cell lung cancer (NSCLC). In the two
individual phase III studies, treatment-naïve
patients with stage IIIB/IV lung adenocarcinoma
and confirmed EGFR mutations in the
tumor were enrolled in LUX-Lung 3 (n=345;
recruited globally) and LUX-Lung 6 (n=364;
recruited in China, Korea and Thailand).
Patients were randomized (2:1) to receive
oral afatinib (40mg/day) or up to six cycles
of intravenous pemetrexed/cisplatin (LUXLung
3) or gemcitabine/cisplatin (LUX-Lung
6) at standard doses. Stratification factors
included EGFR mutation type (Del19 v.
L858R v. other “uncommon” mutations) and
race (Asian v. non-Asian; LUX-Lung 3 only).
Results from both trials showed similar OS
in the afatinib and chemotherapy arms in
the overall NSCLC EGFR mutation-positive
population (LUX-Lung 3: median OS 28.2 to
28.2 months, HR 0.88; p=0.39); (LUX-Lung
6: median OS 23.1 to 23.5 months, HR 0.93;
p=0.61). There was a survival benefit of
more than a year (LUX-Lung 3: median OS
33.3 to 21.1 months; HR 0.54; p=0.0015);
(LUX-Lung 6: median OS 31.4 to 18.4
months; HR 0.64; p=0.0229).
CytRx reported results of a phase IIb
study of aldoxorubicin compared with
doxorubicin as first-line therapy in subjects
with metastatic, locally advanced or
unresectable soft tissue sarcomas (STS). In
this randomized, open-label, 123-subject,
31-center, phase IIb trial, subjects with
advanced soft tissue sarcomas were
randomized 2:1 to receive either
350mg/m2 of aldoxorubicin (83 subjects) or
75mg/m2 of doxorubicin (40 subjects) every
three weeks for up to six cycles. Subjects
were then followed every six weeks with CT
scans to monitor tumor size. The OS results
in 123 patients showed aldoxorubicin-treated
patients demonstrated a 27%
reduction in the risk of death compared to
patients treated with doxorubicin (HR 0.73:
95% confidence interval 0.44-1.20), the
current standard-of-care in this indication.
In addition, aldoxorubicin-treated patients
demonstrated a 41% likelihood of surviving
more than two years, a two-fold increase,
compared to a 20% probability for doxorubicin-
treated patients. Median overall survival
was 16 months (95% confidence interval
13.1-not reached) for aldoxorubicin-treated
patients v. 14.4 months (95% confidence
interval 8.7-20.9) for doxorubicin-treated
patients (p=0.21). For treatment-naive
patients, representing 90% of the patients in
the clinical trial, median overall survival was
16 months (95% confidence interval
13.1-not reached) for aldoxorubicin-treated
patients v. 14 months (95% confidence
interval 8.7-20.1) for doxorubicin treated
patients (p=0.14). Progression-free survival
(PFS) results demonstrated treatment with
aldoxorubicin increased median PFS approximately
79% to 8.4 months, compared
to 4.7 months with doxorubicin, meeting
the study’s primary endpoint (HR=0.419;
p=0.0007). In blinded central radiology
review, PFS results demonstrated treatment
with aldoxorubicin increased median
PFS approximately 104% to 5.7 months,
compared to 2.8 months with doxorubicin,
also meeting the study’s primary endpoint
February 2, 2015
Medivation and Astellas Pharma reported
results of a phase II study comparing
enzalutamide with bicalutamide in men with
metastatic castration-resistant prostate cancer.
The phase II TERRAIN trial enrolled 375 patients
in North America and Europe. The trial involved
patients with metastatic prostate cancer whose
disease progressed despite treatment with a
luteinizing hormone-releasing hormone (LHRH)
analogue therapy or following surgical castration.
The trial was designed to evaluate enzalutamide
at a dose of 160mg taken once daily
v. bicalutamide at a dose of 50mg taken once
daily, the approved dose in combination with an
LHRH analogue. The study achieved its primary
endpoint demonstrating a statistically significant
increase in progression-free survival (PFS) for
enzalutamide compared to bicalutamide (Hazard
Ratio=0.44; 95% Confidence Interval, 0.34-
0.57; p<0.0001). Median PFS was 15.7 months
in the enzalutamide group compared to 5.8
months in the bicalutamide group. The median
time on treatment in TERRAIN was 11.7 months
in the enzalutamide group v. 5.8 months in the
bicalutamide group. Serious adverse events
were reported in 31.1% of enzalutamide-treated
patients and 23.3% of bicalutamide-treated patients.
Grade 3 or higher cardiac adverse events
were reported in 5.5% of enzalutamide-treated
patients v. 2.1% of bicalutamide-treated patients.
Two seizures were reported in the enzalutamide
group and one in the bicalutamide group. The
most common side effects occurring during
treatment and more common in the enzalutamide-
treated v. bicalutamide-treated patients
included fatigue, hot flush, hypertension, diarrhea,
weight decreased and pain in extremity.
PharmaEngine released results of a phase II
study of PEP02 (MM-398, liposome irinotecan
injection) in unresectable metastatic colorectal
cancer (mCRC). The PEPCOL study evaluated
the efficacy and safety of PEP02 (MM-398) in
combination with 5-FU/LV (FUPEP regimen)
or irinotecan plus 5-FU/LV (FOLFIRI regimens:
FOLFIRI-1 or modified FOLFIRI-3) as a secondline
therapy in patients with mCRC. The primary
endpoint was the objective response rate (ORR).
Fifty-five patients were randomized (FUPEP,
n=28; FOLFIRI, n=27) and non-comparative randomly
assigned to FUPEP (PEP02 80mg/m² d1,
folinic acid (FA) 400mg/m² d1, 5-FU 2,400mg/m²
d1-2) or FOLFIRI (FOLFIRI-1: irinotecan 180mg/
m² d1, FA 400mg/m² d1, 5-FU bolus 400mg/m²
d1, 5-FU infusion 2,400mg/m² d1-2; or modified
FOLFIRI-3: irinotecan 90mg/m² d1 and 3,
FA 400mg/m² d1, 5-FU infusion 2,400mg/m²
d1-2). Bevacizumab q2w (5mg/kg) was allowed
in both arms as of June 2012. In the intent to
treat population, the ORR of the FUPEP regimen
was 14% (4/28), which compared favorably with
FOLFIRI-1 (0%, 0/10) and was comparable to the
modified FOLFIRI-3 regimen (18%, 3/17). Most
common grade 3-4 adverse events reported in
the respective FUPEP and the FOLFIRI arms were
neutropenia (11% v. 30%) and diarrhea (21% v.
33%), which were numerically lower in the FUPEP
arm than in the FOLFIRI arm; other aspects
of the safety profiles were similar between the
two arms. Based on the acceptable safety profile
of the FUPEP regimen in this PEPCOL study,
it was added as the third arm to the phase III
metastatic pancreatic cancer (NAPOLI-1) study in
which this FUPEP regimen (MM-398 + 5-FU/LV
arm) met the primary endpoint of a statistically
significant improvement in overall survival.
January 26, 2015
PharmaEngine released results of a
phase III study of MM-398 (PEP02, liposome
irinotecan injection) for metastatic pancreatic
cancer. The global, randomized, openlabel
study evaluated two MM-398 regimens,
80mg/m2 combined with 5-fluorouracil (5-
FU) and leucovorin (LV) every two weeks, and
120mg/m2 as a monotherapy every three
weeks. Each arm was compared to a control
arm of 5-FU and LV. A total of 417 patients
were randomized across the three arms. Each
MM-398 regimen was compared against the
control arm on the primary endpoint of overall
survival. Patients were enrolled at 76 sites
of the 105 sites initiated in North America,
South America, Europe, Asia and Australia.
The primary analysis demonstrated a statistically
significant increase in overall survival
with an unstratified hazard ratio of 0.67 (95%
CI [0.49-0.92], p=0.0122) and a median of
6.1 months for the combination of MM-398
plus 5-FU/LV compared to 4.2 months in the
5-FU/LV control arm. In the stratified analysis,
which accounts for pre-specified prognostic
factors included in the study randomization
stratification, the overall survival for MM-398
in combination with 5-FU/LV compared to
control arm resulted in a hazard ratio of 0.57
(95% CI [0.41-0.80], p=0.0009). In the Per
Protocol population (defined by patients
who received 80% of protocol defined dose
and were able to remain on treatment for
at least six weeks), MM-398 in combination
with 5-FU/LV demonstrated superior overall
survival and tumor control to the control arm
of 5-FU/LV alone. In the Per Protocol analysis,
median overall survival for the combination
therapy arm was 8.9 months versus 5.1
months in the control arm (stratified HR =
0.47, 95% CI [0.29-0.77], p=0.0018).
January 12, 2015
OncoGenex Pharmaceuticals reported
results of a phase II study of apatorsen in
combination with gemcitabine/cisplatin chemotherapy
compared to chemotherapy alone
in the treatment of metastatic bladder cancer.
The trial, Borealis-1, enrolled approximately
180 patients with documented metastatic or
locally inoperable transitional cell carcinoma
(TCC) of the urinary tract who previously
had not received chemotherapy for metastatic
disease and were not candidates for
potentially curative surgery or radiotherapy.
Patients were randomized to receive standard
chemotherapy (gemcitabine/cisplatin) in
combination with apatorsen at two dose levels
(600mg and 1,000mg) or gemcitabine/cisplatin
plus placebo. Patients received up to six
cycles of weekly intravenous therapy. Overall
trial results indicated the addition of 600mg
apatorsen to standard of care chemotherapy
showed a 14% reduction in risk of death
(overall survival hazard ratio (HR) = 0.86) and
a 17% reduction in progressive disease and
death (progression-free survival HR = 0.83)
when compared to chemotherapy alone. Over
one-third of the patients in the trial had lower
performance status, as defined by a Karnofsky
score of 80% or less. These patients derived
the greatest benefit from 600mg apatorsen
in combination with chemotherapy, resulting
in a 50% reduction in risk of death (overall
survival HR = 0.50) compared to chemotherapy
alone. Less benefit was observed in
the 1000mg apatorsen arm due to increased
adverse events leading to a higher rate of discontinuation
of both apatorsen and chemotherapy.
Apatorsen 600mg was well tolerated
in combination with chemotherapy.
December 1, 2014
GlaxoSmithKline reported results of a
phase III study of trametinib (Mekinist)
and dabrafenib (Tafinlar) compared to
vemurafenib monotherapy in previously
untreated patients with BRAF V600E/K mutation-
positive metastatic melanoma. This phase
III, randomized (1:1), open-label study enrolled
704 patients globally. The study demonstrated
a 31% decrease in the risk of death for patients
treated with the trametinib and dabrafenib
combination compared to vemurafenib
(Hazard Ratio [HR] 0.69; 95% Confidence Interval
[CI] 0.53, 0.89; two-sided P=0.005). Median
OS for the vemurafenib arm was 17.2 months;
median OS for the combination arm had not
been reached. At 12 months, the rate of OS
was 72% for the combination arm and 65%
for the vemurafenib arm. Treatment with the
combination increased median progressionfree
survival to 11.4 months compared to 7.3
months for the vemurafenib arm. Overall, treatment
with the combination resulted in a 44%
reduction in risk of disease progression or death
(HR, 0.56; 95% CI 0.46, 0.69; two-sided P-value
<0.001) compared to vemurafenib. The objective
response rate was 64% (95% CI 59.1%,
69.4%) for the combination and 51% (95% CI
46.1%, 56.8%) for vemurafenib (P<0.001); the
median duration of response was 13.8 months
(95% CI 11.0, not reached) v. 7.5 months (95%
CI 7.3, 9.3), respectively. Additionally, 13% of
patients treated with the combination achieved
a complete response, compared to 8% of
patients in the vemurafenib arm.
November 10, 2014
Bristol-Myers Squibb reported results
from a phase II, single-arm, open-label study
of Opdivo (nivolumab) in patients with
advanced squamous cell non-small cell lung
cancer (NSCLC) who have progressed after
at least two prior systemic treatments with
65% receiving three or more prior therapies
(n=117). The trial, Checkmate -063, was
designed to assess advanced squamous cell
NSCLC patients who progressed after both
platinum-based therapy and at least one
additional systemic therapy, with an ECOG
Performance Status of zero or one. Subjects
were treated with Opdivo as a single agent
3mg/kg by intravenous infusion every two
weeks until disease progression or treatment
discontinuation (n=117). With approximately
11 months of minimum follow up, the objective
response rate (ORR, the study’s primary
endpoint) was 15% (95% CI = 8.7, 22.2) as assessed
by an independent review committee
(IRC) using RECIST 1.1 criteria, and the median
duration of response was not reached.
The estimated one-year survival rate was
41% (95% CI = 31.6, 49.7) and median overall
survival (mOS) was 8.2 months (95% CI =
6.05, 10.91). Grade 3-4 drug-related adverse
events (AEs) were reported in 17.1% of
patients. The most common Grade 3-4 AEs
(greater than or equal to 2%) were fatigue
(4.3%), pneumonitis (3.4%) and diarrhea
(2.6%). Discontinuations due to drug-related
AEs of any grade occurred in 12% of patients,
and there were two drug-related deaths in
patients with multiple co-morbidities and in
the setting of progressive disease.
October 20, 2014
Boehringer Ingelheim issued results
of a phase III trial of afatinib v. erlotinib in
patients with advanced squamous cell carcinoma
(SCC) of the lung. In the randomized,
open-label trial, 795 patients with stage
IIIB/IV SCC of the lung were randomized 1:1
to receive afatinib or erlotinib until disease
progression. The planned primary analysis
was based on 414 progression-free survival
(PFS) events by independent review in the
first 669 patients randomized (afatinib:
335, erlotinib: 334) while recruitment was
ongoing. Afatinib significantly reduced the
risk of disease progression by 18% when
compared to erlotinib and delayed tumor
growth (PFS by independent review: 2.4 v.
1.9 months; HR=0.82; p=0.043). Treatment
with afatinib showed improvement in the
secondary endpoint of disease control rate
(DCR) compared to erlotinib (DCR: 45.7%
v. 36.8%; p=0.020). Objective response
rate was 4.8% in the afatinib arm v. 3% in
the erlotinib arm (p=0.233). More patients
reported an improvement in their global
health status/quality of life (p=0.026) and
cough (p=0.01) with afatinib v. erlotinib; no
difference was observed with pain (p=1.0)
and dyspnea (p=0.298) between groups.
There was no significant difference in the
time to deterioration across these four measures.
The overall rate of severe (>/= grade
3) adverse events was comparable between
both therapies. Incidence of severe adverse
events was 50.2% in patients treated with
afatinib compared to 49.1% with erlotinib.
A higher incidence of severe diarrhea and
stomatitis was observed in patients treated
with afatinib compared to erlotinib (severe
diarrhea: 9% v. 2%; stomatitis: 3% v. 0%),
while there was a higher incidence of severe
rash/acne observed with erlotinib compared
to afatinib (9% v. 6%).
Puma Biotechnology issued results of
a phase II trial of PB272 (neratinib) for the
treatment of non-small cell lung cancer
(NSCLC) with HER2 mutations. In the trial,
patients with confirmed stage IIIB or stage
IV NSCLC with documented somatic HER2
mutations were randomized to receive
either oral neratinib monotherapy, 240mg
per day, or the combination of oral neratinib,
240mg daily, with intravenous temsirolimus
administered at a dose of 8mg per
week. A total of 27 patients completed the
first stage of the trial; 13 of these patients
received neratinib monotherapy and 14 of
these patients received the combination of
neratinib plus temsirolimus. Results showed
that of the 13 patients who received neratinib
monotherapy, no patient experienced
a partial response, seven (54%) patients
achieved stable disease and four (31%)
patients achieved clinical benefit (defined
as a partial response or stable disease for
12 or more weeks). For the 14 patients who
received the combination of neratinib plus
temsirolimus, three (21%) patients experienced
a partial response, 11 (79%) patients
experienced stable disease and nine (64%)
patients achieved clinical benefit. The
median progression free survival of the
neratinib monotherapy arm was 2.9 months
and the median progression free survival of
the arm that received neratinib plus temsirolimus
was four months. Patients continue
to be enrolled in the arm of the trial that is
receiving the combination of neratinib plus
October 13, 2014
Janssen R&D issued results of a phase
III study of ZYTIGA (abiraterone acetate)
plus prednisone in men with chemotherapynaive
metastatic castration-resistant prostate
cancer (mCRPC). The international, randomized,
double-blind, placebo-controlled study
included 1,088 men with mCRPC who had
not received prior chemotherapy and were
randomized to receive ZYTIGA (abiraterone
acetate) 1,000mg administered orally once
daily plus prednisone 5mg twice daily or
placebo plus prednisone 5mg twice daily. The
study demonstrated a 19% reduction in risk
of death in this study population (median OS,
34.7 v. 30.3 months, respectively; HR= 0.81
[95% CI, 0.70-0.93]; p = 0.0033), after a median
follow-up of more than four years (49.2
months). 67% of men in the ZYTIGA plus
prednisone arm and 80% in the control arm
received subsequent therapy. This includes
44% of men in the control arm who subsequently
received ZYTIGA plus prednisone.
The use of subsequent therapies did not impact
the statistical significance between the
ZYTIGA and control arms and makes these
results all the more compelling after adjusting
for the crossover effect. Final analysis
demonstrated a significant improvement in
median time to opiate use for cancer-related
pain compared to placebo plus prednisone
(median 33.4 v. 23.4 months, respectively;
HR= 0.72 [95% CI, 0.61-0.85]; p = 0.0001).
With two additional years (a total of four
years) of follow-up since the last clinical cutoff
(median 49.2 months), the safety profile
of ZYTIGA remained unchanged compared to
previous reports. Janssen has initiated regulatory
submissions to health authorities for a
revision to the ZYTIGA label.
October 6, 2014
Bristol-Myers Squibb released results of
a phase III trial of Opdivo (nivolumab) v.
investigator’s choice chemotherapy (ICC) in
patients with advanced melanoma who were
previously treated with Yervoy (ipilimumab).
In the randomized, controlled, open-label
study (n=370), patients were randomized
2:1 to receive Opdivo 3mg/kg by intravenous
infusion every two weeks (n=268) or ICC (dacarbazine
1000mg/m2 every three weeks or
carboplatin [AUC] 6 plus paclitaxel 175mg/
m2 every three weeks; n=102) until progression
or unacceptable toxicity. The objective
response rate (ORR) was 32% (95% CI = 24,
41) in the Opdivo arm and 11% (95% CI = 4,
23) in the ICC reference arm in patients with
at least six months of follow up. The majority
of Opdivo treatment-related adverse events
(AEs) were grade 1/2 and managed using
recommended treatment algorithms. Grade
3/4 drug-related AEs were less frequent for
the Opdivo arm (9% versus 31% of patients
treated chemotherapy). Serious Grade 3/4
drug-related AEs were reported in 5% and
9% of patients treated with Opdivo and ICC,
respectively. Discontinuations due to drug-related
AEs, of any grade, occurred in 2% of
Opdivo-treated patients and 8% of patients
Genentech reported results of a phase
III trial of cobimetinib in combination with
vemurafenib in previously untreated patients
with unresectable locally advanced or metastatic
melanoma harboring a BRAF V600 mutation.
The trial was an international, randomized,
double-blind, placebo-controlled study
evaluating 60mg once daily of cobimetinib
in combination with 960mg twice daily of
vemurafenib, compared to 960mg twice
daily of vemurafenib alone. In the study, 495
patients with BRAF V600 mutation-positive
unresectable locally advanced or metastatic
melanoma, and previously untreated for
advanced disease, were randomized to
receive vemurafenib every day on a 28-day
cycle plus either cobimetinib or placebo for
days 1-21. Median follow up was 7.4 months
for the combination arm and 7.2 months
for the control arm. The median PFS was 9.9
months for the combination of cobimetinib
and vemurafenib v. 6.2 months for vemurafenib
alone (hazard ratio [HR]=0.51, 95%
CI 0.39-0.68; p<0.0001), demonstrating the
combination reduced the risk of the disease
worsening by half (49%). The median PFS
by independent review committee (IRC), a
secondary endpoint, was 11.3 months for the
combination arm compared to six months for
the control arm (HR=0.60, 95% CI 0.45-0.79;
p=0.0003). Objective response rate (ORR) was
68% for the combination v. 45% for vemurafenib
alone (p<0.0001). Overall survival
data are not yet mature (HR=0.65, 95% CI
0.42-1.00; p=0.046). Roche has submitted
an MAA to the EMA, and Genentech plans to
submit an NDA to the FDA later this year.
August 25, 2014
Austrianova released results of a phase II
study of Cell-in-a-Box combined with ifosfamide
for treatment of advanced, inoperable
cancer. Thirteen patients with advanced, inoperable
pancreatic cancer have been treated
with the Cell-in-a-Box/ifosfamide combination
in the uncontrolled (no comparator arms),
open-label study. A single implantation of
Cell-in-Box capsules (each capsule contained
approximately 10,000 cells capable of converting
the anticancer prodrug ifosfamide into its
“cancer-killing” form by virtue of their overexpression
of an isoform [CYP2B1] of human
cytochrome P450) was used and two courses
of treatment with ifosfamide were administered.
There were no deleterious effects, such
as inflammation or pancreatitis, that could be
attributed to the Cell-in-a-Box capsules being
implanted in the patients. The median survival
of patients in the phase I/II clinical trial was
about 40 weeks versus the 33 weeks seen in
the phase II clinical trial. The percentage of
patients who survived one year was somewhat
lower in the phase II clinical trial (23%) than in
the phase I/II clinical trial (38%). The dose (1g/
m2) of ifosfamide used in the phase I/II clinical
trial was one-third of the “normal” dose of
ifosfamide, whereas the dose used in the phase
II clinical trial was twice (2g/m2) that dose. A
phase IIb trial has been planned in Australia
implementing the 1g/m2 dose of ifosfamide
instead of the 2g/m2 dose.
August 11, 2014
Amgen and Onyx Pharmaceuticals
reported results of a phase III study of Kyprolis (carfilzomib) for injection in combination with Revlimid (lenalidomide) and low-dose dexamethasone (KRd) for multiple myeloma. Patients were randomized to receive Kyprolis (20mg/m on days one and two of cycle one only, then 27mg/m subsequently), in addition to a standard dosing schedule of lenalidomide (25mg per day for 21 days on, seven days off) and low-dose dexamethasone (40mg per week in four week cycles), versus lenalidomide
and low-dose dexamethasone alone. The study randomized 792 patients at sites in North America, Europe and Israel. Patients treated with Kyprolis for injection in combination
with Revlimid and low-dose dexamethasone
lived significantly longer without their disease worsening (median 26.3 months) compared to patients treated with Revlimid and low-dose dexamethasone (Rd) (median 17.6 months) (HR=0.690, 95% CI, 0.570, 0.834, p<0.0001). Treatment discontinuation due to adverse events and on-study deaths were comparable between the two arms. These results will form the basis for regulatory submissions
throughout the world beginning in the first half of 2015.
August 4, 2014
Celsion released result of an ongoing, open-label
phase II trial of ThermoDox in recurrent
chest wall breast cancer (RCWBC). The trial is
designed to enroll 20 patients at several U.S.
clinical sites and is evaluating ThermoDox in
combination with mild hyperthermia. Of the 13
patients enrolled and treated, 10 were eligible
for evaluation of efficacy. To date, 60% of patients
experienced a stabilization of their highly
refractory disease with a local response rate
of 50% observed in the 10 evaluable patients,
notably three complete responses, two partial
responses and one patient with stable disease.
July 14, 2014
Taiho Oncology issued results of a
phase III trial of TAS-102 (trifluridine
and tipiracil hydrochloride) for the treatment
of refractory metastatic colorectal
cancer. The trial was a global, randomized,
double-blind, placebo-controlled comparison
trial. The trial enrolled 800 patients in
North America, Japan, Europe and Australia
who received at least two prior regimens
of standard chemotherapies for mCRC and
were refractory to, or failed, those chemotherapies.
Patients were randomized (2:1)
to receive TAS-102 (35mg/m2) or placebo,
plus best supportive care, twice daily.
The trial met the primary efficacy endpoint
of statistically significant improvement in
overall survival versus placebo (H =0.68,
p<0.0001). TAS-102 reduced the risk of
mortality by 32% when compared to
placebo. Median overall survival was 7.1
months (95% CI: 6.5-7.8) and 5.3 months
(95% CI: 4.6-6.0) for TAS-102 and placebo,
respectively, and was improved in favor
of TAS-102 by 1.8 months. There also was
a statistically significant 52% decrease in
the risk of disease progression between
the two arms (HR=0.48, p<0.0001). In
addition, the disease control rate of
patients treated with TAS-102 was 44.0%
versus 16.3% for patients treated with
placebo (p<0.0001). Taiho plans to submit
regulatory submissions in the U.S. at the
end of 2014 and in Europe in the first
quarter of 2015.
June 23, 2014
Novartis reported phase I trial results
of Zykadia (LDK378) in patients with
anaplastic lymphoma kinase-positive (ALK+)
non-small cell lung cancer (NSCLC). The 246
patients with ALK+ NSCLC in this single-arm
study received ceritinib 750mg ALK+ daily.
Findings from the study showed patients
treated with ceritinib achieved an ORR of
58.5% [95% CI, 52.1-64.8%] and a median
PFS of 8.2 months [95% CI, 6.7-10.1 months].
The median duration of response was 9.7
months [95% CI, 7.0-11.4 months], with a
median time to first response of six weeks
after starting treatment. Among 163 patients
receiving 750 mg of ceritinib daily and who
were previously treated with the commonly
prescribed ALK inhibitor crizotinib, ORR
was 54.6% [95% CI, 46.6-62.4%] and PFS
was 6.9 months [95% CI, 5.4-8.4 months].
In 83 patients who had not received prior
treatment with an ALK inhibitor, ORR was
66.3% [95% CI, 55.1-76.3%] and PFS had
not been reached. In the 124 patients who
started the study with brain metastases,
ceritinib achieved an ORR of 54.0% [95% CI,
44.9-63.0%] and a median PFS of 6.9 months
[95% CI, 5.4-8.4 months]. Tumor shrinkage
was seen in 50.0% of patients [49 of
98 patients; 95% CI, 39.7-60.3%] with brain
metastases who had received previous ALK
inhibitor therapy, while 69.2% of patients
[18 of 26 patients; 95% CI, 48.2-85.7%] with
brain metastases who were not previously
treated achieved tumor shrinkage following
treatment with ceritinib.
June 2, 2014
Boehringer Ingelheim reported result
of two phase III trials (LUX-Lung 3 and
LUX-Lung 6) of afatinib for treatment
of advanced non-small cell lung cancer
(NSCLC) with epidermal growth factor
receptor (EGFR) mutation. The LUX-Lung 3
trial compared afatinib with chemotherapy
(pemetrexed/cisplatin); LUX-Lung 6
evaluated afatinib v. chemotherapy
(gemcitabine/cisplatin) for Asian patients.
Afatinib prolonged survival of lung cancer
patients whose tumors have common
EGFR mutations compared with standard
chemotherapy by a median of three months
(27.3 to 24.3 months) and significantly
reduced the risk of death by 19% (HR=0.81,
p=0.037). The most pronounced reduction
in risk of death was 41% (HR=0.59, CI 0.45,
0.77) in patients whose tumors have the
most common EGFR mutation (exon 19
deletion of the EGFR gene); for patients
with the exon 21 (L8585R) mutation
there was no impact on overall survival
(HR=1.25, CI 0.92, 1.71). Those patients
who continued afatinib treatment, with
the addition of chemotherapy, after
progressing on afatinib alone, had a further
delay in tumor growth compared to the
group who stopped afatinib treatment
and received chemotherapy only (tumor
growth was delayed by 5.6 months and
2.8 months respectively, p=0.003). This
corresponded to a 40% reduction in risk of
disease progression (HR=0.60). The most
common adverse events in patients treated
with afatinib and chemotherapy versus
chemotherapy were diarrhea (53.8% v.
6.7%), hair loss or alopecia (32.6% v. 15%)
and weakness or asthenia (27.3% v. 28.3%).
April 28, 2014
GlaxoSmithKline and Genmab released
results of a phase III study of Arzerra (ofatumumab),
in combination with chlorambucil
for previously untreated patients with chronic
lymphocytic leukemia (CLL). Results from the
randomized, open-label, parallel-arm, pivotal
phase III study evaluating the combination
of ofatumumab and chlorambucil (N=221) v.
chlorambucil alone (N=226) demonstrated
statistically significant improvement in median
PFS in patients randomized to ofatumumab
and chlorambucil compared to patients randomized
to chlorambucil alone (22.4 months
v. 13.1 months, respectively) (HR=0.57 [95%
CI, 0.45, 0.72] <0.001). The majority of adverse
reactions (ARs) were Grade 2 or lower in both
treatment arms. The most common (>/=5% in
the ofatumumab plus chlorambucil arm and
also >/=2% more than in the chlorambucil
monotherapy arm) non-infusion-related ARs
(all grades) as reported by investigators within
60 days following the last treatment were
neutropaenia (27% ofatumumab + chlorambucil,
18% chlorambucil), asthaenia (8%, 5%),
headache (7%, 3%), leukopaenia (6%, 2%),
herpes simplex (6%, 4%), lower respiratory tract
infection (5%, 3%), arthralgia (5%, 3%) and upper
abdominal pain (5%, 3%).
April 14, 2014
Synta Pharmaceuticals issued interim
results from a single-arm, multi-center, phase
II proof-of-concept study designed to evaluate
ganetespib for the treatment of metastatic
breast cancer. Target enrollment is 35 patients
in three cohorts, which include HER2+ breast
cancer, triple-negative breast cancer (TNBC)
and, recently added and now recruiting,
ER/PR-positive patients previously untreated
for locally advanced or metastatic disease.
The goal of the trial design is to obtain initial
evidence of a clinical activity signal with
single-agent ganetespib administered for
up to 12 weeks. Ten patients were enrolled
into the HER2+ cohort and 38 patients were
enrolled into the TNBC cohort. Of the patients
evaluable for metabolic response based on
having reached the week 3 PET assessment,
six of seven achieved a metabolic response
in the HER2+ cohort and 18 of 31 achieved
a metabolic response in the TNBC cohort.
Of the 6 HER2+ and 26 TNBC patients that
reached the six-week assessment and therefore
evaluable for objective RECIST response, four
achieved an objective response and two
achieved stable disease in the HER2+ cohort,
while two achieved an objective response, 11
achieved stable disease and 13 had progressive
disease in the TNBC cohort. One HER2+ patient
achieved a complete objective response and
has remained on treatment for over 10 months.
April 7, 2014
Novartis released results of a phase I
study of LDK378 in 130 patients for the
treatment of advanced anaplastic lymphoma
kinase positive (ALK+) non-small cell
lung cancer (NSCLC). Of 114 ALK+ NSCLC
patients treated with LDK378 at 400mg or
higher per day, 80 had progressed during
or following treatment with crizotinib,
and 34 patients with ALK+ NSCLC were
crizotinib-naive. The maximum tolerated
dose observed in the study was 750mg
per day. The median duration of response
for the 66 responding patients treated at
400mg or higher per day was 8.2 months
[95% CI; 6.9-11.4 months]. In all, 114 ALK+
NSCLC patients treated at 400mg or higher
per day, median progression-free survival
was 7 months [95% CI; 5.6-9.5 months]. In
the 114 ALK+ NSCLC patients treated with
LDK378 at 400mg or higher per day, the
overall response rate (ORR) was 58% [95%
CI; 48-67%] (1 complete response [CR] and
65 partial responses [PR]), which includes
those patients who had progressed during
or after crizotinib therapy (ORR 56% [95%
CI; 45-67%]) and those who were crizotinibnaive
(ORR 62% [95% CI; 44-78%]). In the
78 patients with ALK+ NSCLC who received
LDK378 at the maximum tolerated dose of
750mg per day, the ORR was 59% [95% CI;
47-70%] (46 PRs), which includes those who
had progressed during or after crizotinib
therapy (ORR 56% [95% CI; 41-70%]) and
those who were crizotinib-naive (ORR
64% [95% CI; 44-81%]). The most frequent
adverse events were nausea (82%), diarrhea
(75%), vomiting (65%), fatigue (47%) and
increased alanine aminotransferase levels
(35%). At the 750mg dose level, 50 of 81
patients (62%) required at least one dose reduction,
of which 32 occurred in cycle three
or later. The FDA has accepted regulatory
filings for LDK378.
March 24, 2014
Amgen issued results of a phase III study of
talimogene laherparepvec in patients with
injectable unresected stage IIIB, IIIC or IV melanoma
compared to granulocyte-macrophage
colony-stimulating factor (GM-CSF). Of the
295 patients treated with talimogene laherparepvec,
almost 4,000 tumor lesions were
tracked. Half of these lesions were injected
with talimogene laherparepvec at least once,
while the rest were not injected, including
visceral tumor lesions. The results showed
a 50% or greater reduction in tumor size in
64% of injected tumors. In addition, one-third
of uninjected non-visceral tumors, and 15%
of visceral tumors, also were reduced by at
least 50%. There were 35 melanoma-related
surgeries performed during this trial, of which
30% successfully removed all residual disease.
The most frequently observed adverse events
in the phase III study were fatigue, chills and
pyrexia. The most common serious adverse
events include disease progression in both
groups, and cellulitis and pyrexia in the talimogene
March 3, 2014
Eli Lilly reported results of a phase III study of
ramucirumab in combination with chemotherapy
in patients with second-line non-small cell
lung cancer (NSCLC). The global, randomized,
double-blind trial compared ramucirumab and
docetaxel to placebo and docetaxel in NSCLC
patients whose disease has progressed after
failure of prior platinum-based chemotherapy
for locally advanced or metastatic disease.
Ramucirumab showed a statistically significant
improvement in overall survival in the
ramucirumab-plus-docetaxel arm compared
to the control arm of placebo plus docetaxel,
and a statistically significant improvement in
progression-free survival in the ramucirumab
arm compared to the control arm. The most
common (>5% incidence) Grade 3 adverse
events on the ramucirumab-plus-docetaxel
arm were decreased white blood cell count
(neutropenia/leukopenia), febrile neutropenia,
fatigue/asthenia and hypertension.
February 17, 2014
Aeterna Zentaris reported results of a
phase II trial of zoptarelin doxorubicin
(AEZS-108) for the treatment of endometrial
cancer. Forty-four patients entered into
the study at eight centers in Germany and
three centers in Bulgaria. Forty-three of
these patients were eligible. Two patients
had a complete remission (5%) and eight
achieved a partial remission (18%). Stable
disease for at least six weeks was observed
in 44%. The median time to progression
(TTP) was seven months and median overall
survival (OS) was 15 months. The most
frequently reported grade 3 or 4 adverse effects
were neutropenia (12%) and leucopenia
(9%). Data showed zoptarelin doxorubicin
has clinically meaningful activity with
low toxicity in women with advanced or recurrent
LHRH receptor positive endometrial
cancer, supporting the principle of receptor
mediated targeted chemotherapy. These
results were the basis of a phase III trial of
zoptarelin doxorubicin, currently enrolling.
Eisai reported positive results of a phase
III trial of lenvatinib for the treatment
of radioiodine-refractory differentiated
thyroid cancer (RR-DTC). The study was a
multicenter, randomized, double-blind,
placebo-controlled, phase III study to compare
the PFS of patients with radioiodinerefractory
differentiated thyroid cancer and
radiographic evidence of disease progression
within the prior 12 months, treated
with once-daily, oral lenvatinib (24mg) v.
placebo. Secondary endpoints of the study
included overall response rate (ORR), overall
survival (OS) and safety. The study enrolled
392 patients at over 100 sites in Europe,
North and South America and Asia. The
preliminary safety analyses showed the
five most common adverse reactions were
hypertension, diarrhea, decreased appetite,
decreased weight and nausea. Based on
positive clinical results, Eisai will submit
marketing authorization applications for
lenvatinib to health authorities in the U.S.,
Japan and Europe.
Medivation and Astellas Pharma
released results of a phase III trial of
enzalutamide in patients with chemotherapy-
naïve metastatic prostate cancer who
have failed androgen deprivation therapy
and have few or no symptoms. The trial
is a randomized, double-blind, placebocontrolled,
multi-national trial that enrolled
more than 1,700 patients at sites in the U.S.,
Canada, Europe, Australia, Russia, Israel and
Asian countries including Japan. The trial
was designed to evaluate enzalutamide at
a dose of 160mg taken orally once daily v.
placebo. Treatment with enzalutamide demonstrated
a statistically significant overall
survival benefit compared with placebo
treatment. Enzalutamide reduced the risk
of death by 29% (HR=0.71). Treatment with
enzalutamide significantly reduced the
risk of radiographic progression or death
by 81% compared with placebo treatment
(HR=0.19). Men taking enzalutamide
experienced a 17-month delay in the time to
initiation of chemotherapy compared with
men taking placebo (28.0 months versus
10.8 months; HR=0.35). Enzalutamide extended
the median time to PSA progression
from 2.8 months (placebo) to 11.2 months
(HR= 0.169). Nearly four out of five patients
in the enzalutamide group experienced a
PSA decline of 50% or more, compared to
less than 4% in the placebo group (78% vs.
3.5%). Regulatory applications to the FDA
will be filed in early 2014.
February 10, 2014
Pfizer issued results of a phase II trial of
palbociclib for the treatment of human
epidermal growth factor receptor 2 negative
(HER2-) locally advanced or newly diagnosed
metastatic breast cancer. The phase
II, multi-center trial, with 101 global sites
participating, was designed to assess the
PFS of palbociclib (125mg once daily for
three out of four weeks in repeated cycles)
in combination with letrozole v. letrozole
alone (2.5mg once daily on a continuous
regimen) in post-menopausal women with
ER+, HER2- advanced breast cancer. PFS is
comprised of time from randomization to
time of disease progression or death from
any cause. A randomized, global phase III
trial (PALOMA-2) in this patient population is
currently enrolling patients.
February 3, 2014
Janssen has issued positive results of a
phase II study of siltuximab for the treatment
of Multicentric Castleman’s Disease
(MCD) in subjects who are HIV-negative and
human herpes virus-8 (HHV-8)-negative. The
multi-national, randomized, double-blind,
placebo-controlled study involved 79 subjects
randomized 2:1 to receive either siltuximab
plus best supportive care (BSC) or placebo plus
BSC until protocol-defined treatment failure,
after which patients taking the placebo could
cross over to un-blinded siltuximab. Half of
the patients on placebo (13 out of 26) crossed
over to siltuximab. The study found more
than one-third of patients in the siltuximab
arm had a durable tumor and symptomatic
response to treatment, compared to none of
the patients who received placebo plus BSC
(34% v. 0%). In looking at the response rate to
treat MCD-related symptoms, 25% of patients
who received siltuximab plus BSC had durable
complete symptom resolution, defined as
100% reduction of baseline overall symptom
scores for at least 18 weeks, compared to none
of the patients who received placebo plus BSC.
These data supported the recent regulatory
filings of siltuximab in the U.S. and E.U.
January 6, 2014
Daiichi Sankyo has released results of phase III trials of edoxaban for the treatment of either acute symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE) or both, in cancer and non-cancer patients. The global, event-driven, randomized, double-blind, parallel-group phase III study involved 8,292 patients in 439 clinical sites across 37 countries. Patients with either a history of cancer (n=563) or with active cancer (n=208) treated with the once-daily factor Xa-inhibitor edoxaban had a numerically lower incidence of recurrent symptomatic venous thromboembolism (VTE) compared to warfarin (3.7% v. 7.1%, respectively; hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.28 to 1.00). Once-daily edoxaban also had a lower incidence of clinically relevant bleeding (major or non-major) compared to warfarin in cancer patients (12.4% v. 18.8%, respectively; HR, 0.64; 95% CI, 0.45 to 0.92). In the subset of 208 patients with active cancer, once-daily edoxaban had a rate of VTE recurrence of 3.7% compared to 7.1% for warfarin (HR, 0.55; 95% CI, 0.16 to 1.85) and an incidence of clinically relevant bleeding of 18.3% compared to 25.3% for warfarin (HR, 0.72; 95% CI, 0.40 to 1.30).
Takeda Pharmaceutical issued results of a phase III study of VELCADE (bortezomib) for the treatment of multiple myeloma (MM) in previously untreated patients. Results showed a higher cumulative dose suggests improved overall survival (OS) (hazard ratio [HR] 0.53; p<0.0001). Patients who received a cumulative dose of VELCADE of 39mg/m2 or greater lived 20 months longer on average than those who received lower cumulative doses (median OS 66.3 months and 46.2 months, respectively). Patients (n=340) treated with the VELCADE-melphalan-prednisone regimen received up to nine six-week cycles (up to 54 weeks) of the combination therapy (cycles 1-4: VELCADE 1.3mg/m2 IV, days 1, 4, 8, 11, 22, 25, 29, 32; cycles 5-9: VELCADE 1.3mg/m2 IV, days 1, 8, 22, 29; all cycles: melphalan 9mg/m2 and prednisone 60 mg/m2). The maximum planned dose of VELCADE was 67.6mg/m2, including 41.6mg/m2 during cycles 1-4 and 26mg/m2 during cycles 5-9. The median cumulative VELCADE dose received was 39mg/m2. OS was longer in patients in the higher (=39 mg/m2) v. lower (<39 mg/m2) cumulative dose group (median 66.3 v. 46.2 months; HR 0.53; p<0.0001). The HR for OS between the two groups, adjusted for age differences, that were significant between the two groups, was 0.56 (p=0.0002). A landmark analysis showed that in patients who survived past the 180-day threshold, OS was longer in the higher (=39mg/m2) v. lower (<39mg/m2) cumulative dose group (median 60.4 v. 50.3 months; HR 0.71; p=0.04).
December 9, 2013
Oncolytics Biotech reported results of
Reolysin in combination with carboplatin
and paclitaxel in patients with second-line
platinum-refractory, taxane-naïve head
and neck cancers. The double-blinded,
randomized study enrolled 167 patients and
showed a median PFS of 94 days in the test
arm (n=62), v. 50 days in the control arm
(n=56). Patients were evaluated for progression
at the first scheduled post-treatment
scan (performed at six weeks, post-cycle
two of therapy). Of 62 patients on the test
arm, 32.3% had progressed, compared with
51.8% of the 56 patients on the control arm
(p=0.04). Of 86 patients with measurable
disease at the first post-treatment scan, the
test arm (n=48) had a statistically significant
increase in tumor shrinkage over the control
arm (n= 38; p=0.049).
Threshold Pharmaceuticals issued results
of a phase I trial of TH-302 in combination
with Avastin (bevacizumab) in patients with
recurrent glioblastoma following bevacizumab
failure. No dose-limiting toxicity has
been reported to date at doses of TH-302 up
to 670mg/m2 plus bevacizumab at 10mg/m2
every two weeks. A total of 19 patients have
been enrolled in the ongoing trial. Of 14
patients evaluable for tumor response, the
median time to progression was 86 days.
46% (95% CI: 18%-74%) of patients were
alive without disease progression after three
months of treatment. Preliminary data in 14
patients showed TH-302 in combination with
bevacizumab was associated with a median
time to progression of 2.8 months. One patient
achieved a complete response and two
patients achieved partial responses. No grade
4 adverse events were observed at any dose.
Two grade 3 adverse events were observed at
340mg/m2 and 670mg/m2 of skin ulceration
and thrombocytopenia, respectively. The
study is continuing to enroll patients.
December 2, 2013
Merck issued results for a phase Ib trial of
MK-3475 for the treatment of advanced
melanoma. The trial is an ongoing, multi-center,
single-arm, open-label study evaluating
MK-3475 monotherapy in more than 1,000
patients with diverse late-stage cancers
lung and melanoma. Three dosing regimens
of MK-3475 were evaluated: 10mg/kg every
two weeks, 10mg/kg every three weeks or
2mg/kg every three weeks. The overall
response rate at five months was 41%
(CI 95%: 32 to 51%); 88% (43/49) of patients
with a partial or complete response showed
no evidence of disease progression. The
maximum ongoing duration of response
recorded was 65 weeks (range 8+ to 65+).
The disease control rate across doses for
patients in the melanoma cohort was 61%
(CI 95%: 52 to 70%), and median progressionfree
survival at time of analysis was 36 weeks.
The company plans to initiate combination
trials this year and in early 2014.
November 18, 2013
Angiochem released results of a phase II
study of ANG1005 in 80 HER2-positive and
HER2-negative breast cancer patients with
brain metastases. Two doses, 650mg/m2
(n=13) and 550mg/m2 (n=67), were evaluated
for intracranial anti-tumor responses
including response rate, progression-free survival
(PFS) and overall survival (OS). ANG1005
adverse events included neutropenia,
fatigue, peripheral neuropathy and mucosal
inflammation. HER2-positive patients (n=36)
achieved PR’s (9, 25%) and stable disease
(SD) (18, 50%) thereby demonstrating
disease control in 75% of those patients. At
550mg/m2, three month PFS was 71% with a
median PFS of 128 days and OS at six months
of 82%. Her2-negative patients (n=44)
achieved PR’s (5, 11%) and SD (17, 32%),
demonstrating disease control in 50% of
patients. In addition, at 550mg/m2, three
months of PFS was 35% with a median PFS
of 84 days and OS at six months of 60%.
Angiochem will advance ANG1005 into a
phase II clinical study in patients with
recurrent high grade gliomas and a phase II
clinical study in HER2-positive breast cancer
patients with brain metastases.
November 11, 2013
Medivation and Astellas Pharma reported results of a phase III trial of enzalutamide in 1,700 men with metastatic prostate cancer that has progressed despite androgen deprivation therapy and who have not yet received chemotherapy. The randomized, double-blind, placebo-controlled, multinational trial enrolled patients at sites in the U.S., Canada, Europe, Australia, Russia, Israel and Asian countries including Japan. The trial was designed to evaluate enzalutamide at a dose of 160mg taken orally once daily v. placebo. Patients treated with enzalutamide demonstrated a statistically significant overall survival advantage compared with patients receiving placebo (p<0.0001). Enzalutamide provided a 30% reduction in risk of death compared with placebo (Hazard Ratio=0.70; 95% confidence interval, 0.59- 0.83). Patients treated with enzalutamide demonstrated a statistically significant radiographic progression-free survival advantage compared with placebo (p<0.0001). Enzalutamide provided an 81% reduction in risk of radiographic progression or death compared with placebo (Hazard Ratio=0.19; 95% confidence interval, 0.15-0.23). The percentage of patients alive in the enzalutamide arm was 72%, as compared with 65% in the placebo arm, at the time of the interim analysis data cut-off date. Treatment with enzalutamide resulted in a calculated point estimate for median overall survival of 32.4 months (95% confidence interval, 31.5 months-upper limit not yet reached) v. 30.2 months (95% confidence interval, 28.0 months-upper limit not yet reached) for patients receiving placebo. Medivation and Astellas will initiate meetings with and submissions to regulatory agencies beginning in early 2014.
October 28, 2013
Acacia Pharma issued results from a phase II study of APD515 for the treatment of xerostomia (dry mouth) in advanced cancer patients. The randomized, double-blind, placebo-controlled, cross-over trial was conducted in 11 centers in the U.K. and Denmark, and enrolled 32 patients with advanced cancer and a persistently dry mouth. Patients received a week of APD515 treatment and a week of placebo, in a randomly assigned order, with a week’s washout in between. Patients graded their symptoms before and after treatment and were asked to record which treatment week they preferred. Patients’ unstimulated salivary flow was measured before and after each treatment period. Subjective scoring was done on a standard 100mm visual analogue scale, where 0 represented no dryness and 100 the worst dryness possible. The average score for mouth dryness was 26.01 after treatment with APD515 and 43.52 after placebo (p=0.0005). Other subjective scores, for oral comfort, difficulty speaking and difficulty swallowing, all showed a significant improvement for APD515 over placebo. The overall number of adverse events was low, with no significant difference between APD515 and placebo.
September 9, 2013
Incyte issued results of a phase II trial of ruxolitinib, its oral JAK1 and JAK2 inhibitor, in combination with capecitabine in patients with recurrent or treatment refractory metastatic pancreatic cancer. The randomized, double-blind, placebo-controlled trial enrolled 136 patients. The hazard ratio (HR) for overall survival (OS) in the intent to treat population was 0.79 (one-sided p=0.12), and in a pre-specified subgroup analysis conducted in patients identified prospectively as most likely to benefit from JAK pathway inhibition, the HR for OS was 0.47 (one-sided p=0.005). Within this subgroup of patients, which represented 50% of the randomized population, six-month survival in the ruxolitinib arm was 42% v. 11% for placebo. Durable tumor responses were observed only in patients receiving ruxolitinib, and ruxolitinib-treated patients achieved a significant improvement in body weight relative to placebo. A phase III trial will be reviewed with the FDA.
August 19, 2013
Boehringer Ingelheim issued results of a phase III study of afatinib in patients with advanced non-small cell lung cancer (NSCLC). Data from the LUX-Lung 3 trial demonstrate superiority of afatinib over chemotherapy considered best-in-class (pemetrexed/cisplatin) in EGFR-mutation positive advanced NSCLC patients. Patients treated with afatinib lived for almost one year (progression-free survival (PFS) of 11.1 months) before their tumor started to grow again compared to just over half a year (PFS of 6.9 months) for those treated with chemotherapy. Patients taking afatinib with the most common EGFR mutations (del19 and L858R, accounting for 90% of all EGFR mutations) lived for well over a year without progression (PFS of 13.6 months) v. just over half a year (PFS of 6.9 months) for those in the comparator arm. Afatinib significantly delayed the time to deterioration for cough (hazard ratio [HR], 0.60; P=0.007) and dyspnoea (HR, 0.68; P=0.015) and showed significantly better mean scores over time in global health status/QoL (P=0 .015) and physical (P<0.001), role (P=0.004) and cognitive (P=0.007) functioning compared with chemotherapy, as measured by standard questionnaires. The LUX-Lung clinical trial program currently involves eight studies designed to investigate the use of afatinib in various settings of advanced NSCLC, including head-to-head trials with the first-wave of reversible tyrosine kinase inhibitors.
August 12, 2013
GlaxoSmithKline issued results of a randomized, double-blind, phase III, placebo controlled trial of pazopanib monotherapy in women with epithelial ovarian, fallopian tube or primary peritoneal cancer whose disease had not progressed after completing standard debulking surgery and first-line chemotherapy. After completion of five or more cycles of platinum-taxane chemotherapy, 940 patients were randomized 1:1 to receive 800mg pazopanib once daily or placebo for up to 24 months (median time from diagnosis to randomization was approximately seven months). Pazopanib treatment reduced the risk of disease progression or death by 23% (HR = 0.77; 95% CI: 0.64-0.91; p = 0.0021). The incidence of serious adverse events was higher in the pazopanib group compared to the placebo group (26% v. 11%). Regulatory applications will be submitted before 2014.
Immunomedics reported results of a phase Ib study of 90Y-labeled-clivatuzumab for the treatment of metastatic pancreatic cancer in 58 patients who had received at least two prior treatments. Patients were randomized to receive either 90Y-labeled-clivatuzumab once a week for three weeks at 6.5mCi/m2 with gemcitabine 200mg/m2 given weekly for four weeks (Arm A) or 90Y-labeled-clivatuzumab alone (Arm B). This treatment cycle was repeated every four weeks until unacceptable toxicity, patient deterioration or patient withdrawal. Patients were followed for one year or until death. The median overall survival (OS) for Arm A (N=27) was 119 days, an improvement over Arm B (N=26), with a median OS of 80 days (P=0.04). For the 23 patients who received multiple cycles of therapy, the median OS increased to 157 days in Arm A compared with 103 days in Arm B. Survival also was related to patients’ Karnofsky Performance Status (KPS) scores at study entry, increasing from a median of 79 days for patients with 80% KPS to 119 days for patients with 90% to 100% KPS. In contrast, increased number of prior treatments is a negative prognostic indicator for survival. The median OS decreased from 90 to 82 to 73 days for patients who received 2, 3 or 4 to 5 prior treatments, respectively. Phase III trials are planned for 2013 or the beginning of 2014 in the U.S. and the E.U.
July 29, 2013
Amgen released results from a phase II study of XGEVA (denosumab) in adults and skeletally mature adolescents diagnosed with giant cell tumor of bone (GCTB). In the international, open-label, phase II study enrolling 282 patients, there were three cohorts: patients with surgically unsalvageable GCTB (Cohort 1), patients with salvageable GCTB whose surgery was associated with severe morbidity (Cohort 2) and patients who transferred from a previous XGEVA GCTB study (Cohort 3). All three cohorts received subcutaneous XGEVA 120mg every four weeks with loading doses on days eight and 15. In Cohort 1, 96% (163/169) of patients had no disease progression after a median follow-up of 13 months. In Cohort 2, 74% (74/100) of patients required no surgery and 62% (16/26) of patients who had surgery underwent a less morbid procedure than planned. XGEVA was approved June 13 by the FDA for the treatment of adults and skeletally mature adolescents with GCTB that is unresectable or where surgical resection is likely to result in severe morbidity.
Bayer HealthCare issued results from a phase III study of Xofigo in castration-resistant prostate cancer (CRPC) patients with symptomatic bone metastases. The randomized, double-blind, placebo-controlled, international study enrolled 921 patients in 100 centers in 19 countries. Patients were stratified based on their baseline alkaline phosphatase (ALP) level, current bisphosphonate use and whether or not they had received docetaxel prior to enrollment. Treatment consisted of up to six intravenous injections separated by four weeks. Xofigo improved overall survival (OS) at the prespecified interim analysis (HR=0.695, [95% CI: 0.552-0.875], p=0.00185); median OS was 14.0 months with Xofigo (95% CI: 12.1-15.8) vs. 11.2 months with placebo (95% CI: 9.0-13.2). These findings were supported by an exploratory analysis performed before patient crossover with an additional 214 events in which Xofigo showed improvement in OS (HR=0.695, [95% CI: 0.581-0.832]); median OS was 14.9 months in the Xofigo arm (95% CI: 13.9-16.1) v. 11.3 months in the placebo arm (95% CI: 10.4-12.8). These data supported the FDA approval of Xofigo injection in May.
July 1, 2013
Amgen reported results from a phase III trial of trebananib plus paclitaxel v. placebo plus paclitaxel for the treatment of recurrent ovarian cancer. This global, multicenter, randomized, double-blind, placebo-controlled study enrolled 900 women with recurrent partially platinum-sensitive or -resistant (platinum-free interval of 12 months or less) epithelial ovarian, primary peritoneal or fallopian tube cancer. Patients were randomized 1:1 to receive either 15mg/kg of intravenous trebananib weekly plus 80mg/m of intravenous paclitaxel weekly (three weeks on, one week off) or weekly intravenous placebo plus 80mg/m of intravenous paclitaxel weekly (three weeks on, one week off). The trial met its primary endpoint of progression-free survival (PFS). A statistically significant difference was observed in PFS with a 34% reduction in the risk of disease progression or death (HR = 0.66, 95% CI, 0.57, 0.77, p<0.001). The median PFS was 7.2 months in the trebananib arm v. 5.4 months in the control arm.
June 24, 2013
Novartis reported results from a phase I trial of LDK378 for anaplastic lymphoma kinase positive (ALK+) metastatic non-small cell lung cancer (NSCLC) in patients who had progressed during or after crizotinib therapy or had not been previously treated with crizotinib. This single-arm study enrolled 114 patients. The results showed an overall response rate of 60% in patients with ALK+ NSCLC taking LDK378 (750 mg/day), which includes patients who had progressed during or after crizotinib therapy (overall response rate of 59%) and those who were crizotinib-naive (overall response rate of 62%). 78 patients were treated at 750mg/day; 36 patients were treated with LDK378 at 400-750mg/day. The median duration of response for patients treated at 400mg/day or higher (n=66) was 8.2 months (95% confidence interval [CI], 6.9-NE), with a median progression-free survival of 8.6 months (95% CI; 5.7-9.9). The six-month duration of response rate at 750mg/day was 61% (95% CI; 34.9-78.8). This trial will serve as the basis for the first regulatory filing, anticipated in early 2014.
June 17, 2013
DelMar Pharmaceuticals reported results from a phase I/II trial of VAL-083 (dianhydrogalactitol) for the treatment of recurrent malignant glioma and progressive secondary brain tumors. Of the three cohorts of patients currently enrolled, all have failed standard therapies and have no viable treatment options. The subjects received VAL-083 at a dose of 1.5mg/m; 3.0mg/m and 5.0mg/m. At these doses, 25% (2/8) of GBM patients and 17% (1/6) of secondary-progressive brain cancer patients showed stable disease or tumor regression in response to treatment. VAL-083 therapy is well tolerated in glioblastoma multiforme (GBM) and secondary-progressive brain tumor patients with no drug-related serious adverse events at doses studied to date. DelMar plans to split the protocol into two separate studies: one focusing solely on refractory glioblastoma and the other focusing on metastatic brain cancers.
Halozyme Therapeutics reported results from a phase Ib trial of PEGPH20 (PEGylated Recombinant Human Hyaluronidase) for the treatment of stage IV metastatic pancreatic cancer. The single-arm phase Ib trial enrolled 28 stage IV treatment naïve pancreatic ductal adenocarcinoma patients. The overall response rate (complete response + partial response) by RECIST 1.1 criteria was 42% (95% CI 22-62) for those treated at therapeutic dose levels of PEGPH20 (1.6 and 3.0μg/kg) as assessed by an independent radiology review (n=24). Additionally, in subjects with high levels of hyaluronan (HA), a substance found in a protective matrix that surrounds many pancreatic cancers, the overall response rate was 64% (seven of 11 subjects with available biopsy). Moreover, 43% (six of 14 subjects) saw a reduction of at least 70% in serum carbohydrate antigen 19-9 (CA 19-9), a biomarker that often correlates with tumor cell burden. Treatment was generally well tolerated, and the adverse event profile was consistent with those seen in previous studies of PEGPH20 as a single agent and as previously reported for gemcitabine alone. The most common adverse events were muscle spasms, myalgia and arthralgia (all grade 1/2). There was no evidence of new toxicities when used in combination with gemcitabine. The results support the dosing regimen at 3μg/kg, being used in the phase II trial.
June 10, 2013
Boehringer Ingelheim issued results from a phase III trial of LUME-Lung 1 for the treatment of advanced non-small cell lung cancer (NSCLC). This randomized, openlabel, double-blind study enrolled 1,314 patients with locally advanced or metastatic (stage IIIb/IV or recurring) NSCLC after first-line therapy. The subjects received nintedanib 200mg BID plus docetaxel 75mg/m(2) once a day for three weeks (n=655), or docetaxel plus placebo (n=659). LUME-Lung 1 improved progression-free survival (PFS)—the primary endpoint—as a second-line treatment in patients with NSCLC compared to docetaxel alone. Secondary endpoints included overall survival. Results showed patients treated with nintedanib plus docetaxel lived for a median of 3.4 months before their tumor started to grow again, versus 2.7 months with docetaxel alone (HR 0.79; p=0.0019). The most common adverse events (AEs) of any grade in the nintedanib combination and docetaxel alone groups were diarrhea (42.3% v. 21.8%, respectively) and ALT elevations (28.5% v. 8.4%, respectively). Incidence of > grade 3 AEs was 71.3% in patients treated with nintedanib plus docetaxel compared to 64.3% with docetaxel alone. A higher incidence of > grade 3 diarrhea and elevated ALT were observed in patients treated with nintedanib plus docetaxel compared to docetaxel alone (> grade 3 diarrhea: 6.6% v. 2.6%; elevated ALT: 7.8% v. 0.9%). Incidence of > grade 3 hypertension, bleeding and thrombosis were similar in both treatment arms. There was a 1% difference in discontinuation between the treatment arms, with 22.7% of patients stopping treatment with nintedanib plus docetaxel versus 21.7% with docetaxel alone.
Novartis reported results from a phase III trial of Afinitor for the treatment of HER2 positive advanced breast cancer. This randomized, double-blind study of everolimus plus trastuzumab and vinorelbine conducted at 159 clinical trial sites globally included 569 women with HER2 positive locally advanced or metastatic breast cancer who were previously treated with a taxane and were resistant to trastuzumab. Subjects received either everolimus 5mg/day orally or placebo, plus weekly vinorelbine 25mg/m IV and weekly trastuzumab 2mg/kg IV following a loading dose of 4mg/kg. The primary endpoint of significantly extended progression-free survival (PFS) when compared to treatment with placebo plus trastuzumab and vinorelbine was met. Final PFS results showed adding everolimus to the standard treatment of trastuzumab and vinorelbine reduced the risk of disease progression by 22% (hazard ratio=0.78 [95% confidence interval (CI):0.65 to 0.95]; p<0.01). Median time to progression was 7.0 months in the everolimus combination arm and 5.8 months in the placebo combination arm. Adverse events were consistent with the known safety profile of everolimus. The most common all-grade adverse reactions (incidence >30%) were neutropenia, stomatitis, anemia, leukopenia, fatigue, pyrexia, diarrhea, nausea, decreased appetite and constipation.
May 20, 2013
Syndax Pharmaceuticals published results from a phase II trial of entinostat for the treatment of estrogen receptor-positive (ER+) breast cancer in the Journal of Clinical Oncology. This randomized, double-blind, placebo-controlled study, ENCORE 301, enrolled 130 postmenopausal women with ER+ breast cancer whose cancer had progressed after treatment with a nonsteroidal aromatase inhibitor. Subjects received 25mg exemestane daily plus 5mg entinostat once per week, or 25mg exemestane plus placebo. Based on intent-to-treat analysis, patients treated with entinostat saw improved median progression-free survival to 4.3 months versus 2.3 months in patients treated with placebo (hazard ratio 0.73; 95% confidence interval, 0.50 to 1.07; one-sided p=.055; two-sided p=.11). Overall survival was an exploratory endpoint, and median survival improved to 28.1 months in entinostat-treated patients versus 19.8 months in placebo-treated (hazard ratio 0.59; 95% confidence interval, 0.36 to 0.97; p=.036). Entinostat was well tolerated. The most frequent adverse events were fatigue and neutropenia. Based on this data, Syndax Pharmaceuticals is working to move entinostat into a confirmatory pivotal study this fall.
April 22, 2013
Activartis reported preliminary results from a phase II trial of AV0113 for the treatment of glioblastoma multiforme (GBM). This multi-center, randomized, placebo-controlled study had enrolled 100 subjects with GBM at the time of analysis. Subjects received standard first-line therapy, plus AV0113 DC-CIT inoculated into inguinal lymph nodes: after six weeks of chemo and radiotherapy, four weekly applications; six more applications every four weeks; and then one boost immunization every three months. Preliminary results revealed a very promising trend suggesting an overall survival benefit of patients in the AV0113 treatment group compared to the randomized control group. At 12 months, 64% of patients in the treatment group and 48% of patients in the control group were still alive. At 18 months, 50% of patients in the treatment and 33% of patients in the control group were still alive. Patients receiving AV0113 cancer immunotherapy tended to experience signs of relapse earlier compared to control patients. AV0113-triggered inflammation in the tumor tissue may explain this observation, which was also made in other clinical trials studying cancer immunotherapy. AV0113 treatment was well tolerated. The most frequent adverse events were local swelling, redness and tenderness at the injection site. Activartis will continue the phase II trial to confirm the observed trend.
April 15, 2013
Navidea Biopharmaceuticals issued interim results from a phase III trial of Lymphoseek (technetium 99m tilmanocept) for identifying sentinel lymph nodes (SLNs) in patients with head and neck squamous cell carcinoma. This open-label, multicenter, within-patient study, NEO3-06, enrolled 80 patients with head and neck squamous cell carcinoma. After receiving a Lymphoseek injection, 39 of the 80 patients were determined to have pathology-positive lymph nodes. Results demonstrated of these 39 patients, Lymphoseek accurately identified 38, for an overall False Negative Rate (FNR) of 2.56%, which was statistically significant (p=0.0205) and met the statistical threshold for success of the primary endpoint. Moreover, multiple-level nodal dissection of patients in the trial with cancer-positive lymph nodes led to an average removal of 38 lymph nodes per patient, whereas Lymphoseek on average led to the removal of approximately four lymph nodes, representing a substantial reduction in potential morbidity for patients with head and neck cancer undergoing sentinel lymph node biopsy. Based on these data, Navidea Biopharmaceuticals will evaluate the possibility of filing a Supplemental New Drug application (sNDA) later this year.
February 4, 2013
Amgen issued results from a phase III trial of Neulasta (pegfilgrastim) for the treatment of colorectal cancer. This multinational, randomized, double-blind, placebo-controlled trial enrolled 845 patients receiving FOLFOX or FOLFIRI and bevacizumab for the first-line treatment of locally-advanced or metastatic colorectal cancer. Subjects received 6mg of Neulasta, or placebo, at least 24 hours after each cycle of chemotherapy. Results showed the study met its primary endpoint: Neulasta significantly reduced the incidence of febrile neutropenia (low white blood cell count accompanied by a fever). In the study, the incidence of grade 3 or 4 febrile neutropenia in patients receiving Neulasta across the first four cycles of chemotherapy was 2.4%, compared to 5.7% in the placebo group (OR=0.41, p=0.014). A similar incidence of grade 3 or higher adverse events was seen in both arms of the trial (28% placebo; 27% Neulasta). The drug was well tolerated. Amgen did not note its plans for Neulasta.
January 28, 2013
Celgene International issued results from a phase III trial of Abraxane in combination with gemcitabine for the treatment of metastatic pancreatic cancer. This open-label, randomized, international study, MPACT, enrolled 861 treatment-naïve patients with metastatic pancreatic cancer. Subjects received 125mg/m2 Abraxane plus 1000mg/m2 gemcitabine for three weeks, followed by a week of rest, or 1000mg/m2 gemcitabine alone for seven weeks, followed by a week of rest. Data demonstrated a statistically significant improvement in overall survival in the Abraxane/gemcitabine arm compared to patients receiving gemcitabine alone (median of 8.5 vs. 6.7 months) (HR 0.72, p=0.000015). Results showed the Abraxane/gemcitabine arm demonstrated a 59% increase in one-year survival (35% versus 22%, p=0.0002) and demonstrated double the rate of survival at two years (9% versus 4%, p=0.02) as compared to gemcitabine alone. Furthermore, the Abraxane/gemcitabine arm demonstrated a 31% reduction in the risk of progression or death with a median progression-free survival of 5.5 versus 3.7 months (HR 0.69, P=0.000024) and an overall response rate of 23% compared to 7%. The drug was well tolerated. The most frequent adverse events were neutropenia, fatigue and neuropathy. Based on these results, Celgene International plans to submit dossiers for registration in the U.S. and Europe during the first half of 2013, followed by submissions in other countries/regions during the second half of 2013.
January 7, 2013
Bristol-Myers Squibb reported results from a phase II trial of elotuzumab in combination with lenalidomide and low-dose dexamethasone for the treatment of multiple myeloma. This randomized, multi-center, open-label study enrolled patients with previously treated multiple myeloma. Subjects received either 10mg/kg or 20mg/kg of elotuzumab intravenously on days 1, 8, 15 and 22 of a 28-day cycle in the first two cycles, and then on days 1 and 15 of subsequent cycles. Subjects also received lenalidomide 25mg PO daily on days 1 to 21 and dexamethasone 40mg PO weekly. Results demonstrated in the 10mg/kg arm, median progression-free survival (PFS) was not reached after 20.8 months of follow up (n=36) and the objective response rate (ORR; according to the International Myeloma Working Group response criteria) was 92%. Of patients who received elotuzumab at a dose of 20mg/kg, median PFS was 18.6 months (n=37) and ORR was 76%. Elotuzumab was well tolerated. The most frequent adverse events were lymphopenia, neutropenia, thrombocytopenia, anemia, leukopenia, hyperglycemia, pneumonia, diarrhea, fatigue and hypokalemia. BMS also is studying elotuzumab in two phase III trials for treatment of relapsed/refractory multiple myeloma.
December 10, 2012
ARIAD Pharmaceuticals released results from a phase I trial of ponatinib for the treatment of resistant and refractory chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). This dose-escalation study enrolled 81 patients with resistant hematologic cancers, including 60 patients with CML and five patients with Ph+ ALL, who had become resistant to one or more tyrosine kinase inhibitors. Results showed that after 73 weeks, 72% of patients (31 of 43) with chronic-phase CML had a major cytogenetic response (MCyR), including 92% (11 of 12) who had the T315I gatekeeper mutation, the most common mutation among resistant patients. In addition, of 22 patients with accelerated-phase or blast-phase CML or Ph+ ALL, 36% (8 of 22) had a major hematologic response and 32% (7 of 22) had aMCyR. The drug was well tolerated. The most frequent adverse events were rash, thrombocytopenia, arthralgia, increased lipase, fatigue, acneiform dermatitis dry skin and nausea. ARIAD did not disclose its plans for ponatinib.
November 28, 2012
Aeterna Zentaris reported results from a phase I trial of perifosine combined with temsirolimus for the treatment of malignant glioma. This combination, dose-ranging study enrolled 32 patients with recurrent or progressive malignant glioma, anaplastic astrocytoma, anaplastic oligodendroglioma and transformed low-grade gliomas with median Karnofsky Performance Status 80. Subjects either received a 600mg or 900mg dose of perifosine on day one, followed by a nightly dose of 100mg of perifosine. All subjects also received 15mg to170mg of temsirolimus once weekly. Preliminary survival results demonstrated that median overall survival was 7.4 months. There were 27 radiographic responses: complete response (0), partial response (2), stable disease (13) and progressive disease (12). The most frequent adverse events were hypophosphatemia, hypocholesterolemia and hypertriglyceridemia. The maximum tolerated dose was not defined, so Aeterna Zentaris is creating expansion cohorts.
OncoSec Medical issued preliminary results from a phase II trial of ImmunoPulse for the treatment of metastatic melanoma. This single-arm, open-label and multi-center study has enrolled 13 patients with stage III or IV cutaneous and in-transit metastatic melanoma, of 25 patients expected. Subjects received a maximum dose of 1.5mg of DNA IL-12 via ImmunoPulse on days one, five and eight, applied to up to four lesions. Subjects also received electroporation treatment. Results suggested that ImmunoPulse is able to induce regression or stabilization of distant untreated metastases following a single cycle of treatment. Ninety-five percent of treated lesions demonstrated response at day 39 (5% progressive disease, 14% stable disease (SD), 42% partial response (PR), 39% complete response (CR)). All treated lesions at day 90 (5% SD, 50% PR, 45% CR), and at day 180 (33% PR, 67% CR) demonstrated a response. At day 180, two subjects were evaluable for the primary endpoint of objective overall response (ORR). One patient has a confirmed stable disease, and the second patient has a confirmed complete response of all treated and untreated lesions. ImmunoPulse and DNA IL-12 were well tolerated. The most frequent adverse events were generally limited to transient pain related to electroporation treatment. OncoSec Medical will continue the phase II study, which it expects to be completed by the end of 2012.
November 12, 2012
MorphoSys and Xencor released results from a phase I/IIa trial of MOR208 (MOR00208/XmAb5574) for the treatment of tumor activity. This dose-ranging study enrolled patients with high-risk, heavily pretreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Subjects received doses ranging from MOR208 0.3mg/kg to 12mg/kg as an intravenous infusion on days 1, 4, 8, 15 and 22 in cycle one, and on days 1, 8, 15 and 22 in cycle two. Overall response rate by International Working Group on CLL (IWCLL) 2008 criteria was 11%, which utilizes more rigorous CT scan reduction of internal lymph nodes not previously required in older historic studies. Using IWCLL 1996 response criteria resulted in a response rate of 42%. MORE208 was well tolerated and found safe. The most frequent adverse events were mild to moderate infusion reactions usually with the first dose. Based on these results, MorphoSys plans to commence phase II studies of MOR208 in B-cell malignancies in the near future.
October 29, 2012
Celgene International reported results from a phase III trial of pomalidomide plus low-dose dexamethasone compared to high-dose dexamethasone for multiple myeloma. This multi-center, randomized, open-label study enrolled patients with relapsed and/or refractory multiple myeloma. Subjects in Arm 1 received 4mg pomalidomide on days 1-21 of each 28-day cycle, with patients 75 years or younger also receiving 40mg of low-dose dexamethasone and patients older than 75 receiving 20mg of low-dose dexamethasone on days 1, 8, 15 and 22 of each 28-day cycle, until disease progression. Subjects in Arm 2 received 40mg high-dose dexamethasone on days 1-4, 9-12 and 17-20 of each 28-day cycle if they were 75 years or younger, and patients older than 75 received 20mg high-dose dexamethasone on days 1-4, 9-12 and 17-20 of a 28-day cycle, until disease progression. The study met its primary endpoint of improvement in progression-free survival (PFS) at the PFS final analysis. Additionally, the study crossed the superiority boundary for overall survival (OS), a key secondary endpoint. As a result, patients who had not yet progressed in the high-dose dexamethasone arm should be crossed-over to the pomalidomide plus low-dose dexamethasone arm. Celgene has submitted an NDA application to the FDA, as well as an MAA application to the EMA.
October 15, 2012
Boehringer Ingelheim released results from a phase III trial of afatinib for the treatment of non-small cell lung cancer (NSCLC). This randomized, open-label study enrolled 345 previously untreated patients with EGFR mutation positive NSCLC. Subjects received afatinib or standard chemotherapy agents (pemetrexed/cisplatin) as first-line treatment. Data showed afatinib-dosed patients had a progression-free survival (PFS) of 11.1 months versus a PFS of 6.9 months for those receiving pemetrexed/cisplatin. NSCLC patients with tumors harboring the two most common EGFR mutations (del19 and L858R) receiving afatinib had a PFS of 13.6 months versus a PFS of 6.9 months for those in the comparator arm. The afatinib-dosed arm experienced an improvement in shortness of breath, cough and chest pain, a delay in deterioration of these symptoms, and overall improved quality of life. Afatinib was well tolerated. Boehringer Ingelheim has initiated two head-to-head trials comparing afatinib to Iressa (gefitinib) and Tarceva (erlotinib), to demonstrate any potential efficacy and safety superiority.
September 17, 2012
ImmunoGen released results from a phase II trial of IMGN901, in combination with etoposide and carboplatin, for the treatment of small cell lung cancer (SCLC). This randomized, dose-finding study, NORTH, enrolled 120 patients. Subjects received etoposide 100 mg/m2 on days one through three every 21 days; carboplatin AUC5 or AUC6 on day one every 21 days; and IMGN901 ranging up to 112 mg/m2, administered on days one and eight every 21 days. Results showed that IMGN901 112 mg/m2, carboplatin AUC5 and etoposide 100 mg/m2 was the most effective dose. Of the 33 patients dosed with this regimen, 10 had an objective response and 24 (72.7%) had disease control (objective response or stable disease). IMGN901 was well tolerated. The most frequent adverse event was low grade peripheral neuropathy.
August 27, 2012
Medivation and Astellas Pharma published results from a phase III trial of enzalutamide for the treatment of metastatic castration-resistant prostate cancer. This international, randomized, double-blind, placebo-controlled study, AFFIRM, enrolled 1,199 men who had been previously treated with docetaxel-based chemotherapy. Subjects received enzalutamide 160mg once daily (as four 40mg capsules), or placebo. Data showed enzalutamide exhibited a statistically significant benefit in overall survival compared to placebo. Men treated with enzalutamide had a median overall survival of 18.4 months (95% confidence interval, 17.3 to not yet reached) compared to 13.6 months (95% confidence interval 11.3-15.8) for men treated with placebo (hazard ratio 0.63; p<0.0001), representing a 37% reduction in the risk of death. The drug was well tolerated. The most frequent adverse events were fatigue, diarrhea and hot flush. Seizure was reported in less than 1% of enzalutamide-treated patients. Neither Medivation nor Astellas noted its next steps for enzalutamide.
July 9, 2012
Synta Pharmaceuticals reported interim results from a phase IIb/III trial of ganetespib in combination with docetaxel for the treatment of advanced non-small cell lung cancer (NSCLC). This multi-arm, randomized, open-label phase IIb part of the GALAXY study enrolled 183 patients to date with stage IIIB/IV NSCLC who have progressed following one prior line of therapy. All subjects received a standard regimen of docetaxel 75mg/m2 on Day 1 of a 21-day cycle; subjects in the combination arm receive in addition ganetespib 150mg/m2 on Day 1 and 15. Both primary endpoints were met based on RECIST 1.1 criteria. Subjects with elevated baseline level of serum LDH (lactate dehydrogenase) who received a combination of ganetespib and docetaxel had a median PFS of 4.2 months, compared to 1.4 months in those treated with only docetaxel; subjects with a tumor KRAS mutation receiving the combination treatment had a median PFS of 4.2 months, while the docetaxel group had a PFS of 1.6 months. The treatment was well tolerated. The most frequent adverse events were neutropenia, diarrhea and fatigue. Synta Pharmaceuticals will continue to enroll more subjects in the phase IIb trial. The transition into phase III is expected later this year.
June 11, 2012
Bayer Healthcare and Onyx Pharmaceuticals released results from a phase III trial of regorafenib for the treatment of metastatic and/or unresectable gastrointestinal stromal tumors (GIST). This randomized, double-blind, placebo-controlled, multi-center, cross-over study, GRID, enrolled 199 patients who had been treated unsuccessfully with imatinib and sunitinib. Subjects received either 160mg regorafenib daily for three weeks followed by a week off plus best supportive care or placebo plus best supportive care. The GRID study met its primary endpoint of improvement in progression-free survival (PFS) (HR≡0.27, p<0.0001). The median PFS was 4.8 months in the regorafenib arm versus 0.9 months in the placebo arm. The most common adverse events included hand-foot skin reaction, hypertension, diarrhea, fatigue, oral mucositis, alopecia, hoarsness and anorexia, among others. Based on these data, Bayer plans to submit an NDA in the second half of 2012.
December 12, 2011
Acacia Pharma issued results from a phase IIa trial of APD209 for cancer cachexia. The trial enrolled 13 subjects with an average weight loss of 11.4% in the previous six months. The subjects received APD209 for eight weeks. The primary efficacy endpoint was major response, defined as an increase in quadriceps muscle size of at least 4% and/or an increase of at least 10% in quadriceps strength. Seven subjects completed the eight week course of treatment, with six achieving a major response. Among the responders, the average increase in quadriceps volume was 6% and quadriceps strength rose on average 16%. Hand grip strength increased on average 17%. Physical activity was also markedly improved in three subjects. In two of these subjects the average daily step count more than doubled between the start and end of treatment. Side effects related to APD209 were generally mild.
April 13, 2009
Oncolytics issued positive results from a phase II trial of Reolysin with low-dose fractionated radiotherapy for the treatment of advanced cancers. This open-label, single-arm, multi-center study, dubbed REO-008, enrolled 16 subjects in the UK. All subjects had advanced or metastatic cancers that are refractory to standard therapy. The subjects receive two intratumoral doses of Reolysin at 1x10(10) TCID(50) with a constant localized radiation dose of 20 Gy in five consecutive daily fractions. The primary endpoint was objective tumor response rate in treated lesions. Secondary endpoints were to evaluate viral replication, immune response, and safety. Of the 16 enrolled subjects, 14 were evaluable for response. Thirteen subjects had stable disease or better in the treated target lesions. Of these, partial responses were observed in four and minor responses were observed in two subjects, for a total disease control rate (stable disease + partial response + complete response) of 93% in the treated lesions. The combination was well tolerated.
March 30, 2009
Oncolytics Biotech issued positive interim results from a phase I/II trial (REO-011) of Reolysin for the treatment of advanced cancer. All subjects had cancer refractory to standard therapy or for which no curative standard therapy exists. The phase I portion of this trial was designed as an open-label, non-randomized study. The subjects received escalating doses of intravenous Reolysin with standard doses of paclitaxel and carboplatin every three weeks. The phase II portion of this trial was a single arm, open-label, dose-targeted, non-randomized design. Fourteen subjects were enrolled and received the determined maximum tolerated dose of Reolysin given intravenously in combination with a standard dosage of paclitaxel and carboplatin. Data is from 15 subjects with head and neck cancer; all but one had prior platinum treatment. Of 12 subjects evaluable for clinical response, 5 had partial response and four had stable disease ranging from two to six months. For the subjects who have been followed for at least six months since their initial treatment, the median progression-free survival is currently six months, while the overall survival is currently seven months.
November 26, 2007
Thallion reported positive results from a phase I/II trial of ECO-4601 for the treatment of advanced cancers. The trial enrolled twenty-six subjects who were refractory to their respective standard of care therapy. ECO-4601 was administered in twenty-one day cycles consisting of a two week continuous intravenous infusion followed by a one week rest period. The trial was conducted in two portions. In the first portion, fourteen subjects received escalating doses ranging from 30 to 480mg/m2/day to assess safety, pharmacokinetics and maximum tolerated dose. In the second portion of the trial, twelve subjects were treated at the highest dose, 480mg/m2/day. Treatment was well tolerated and the maximum target dose was attained before the maximum tolerated dose was reached. Pharmacokinetic data demonstrated that estimated therapeutic plasma concentrations of ECO-4601 were reached at the higher doses and that ECO-4601 was rapidly eliminated from the bloodstream following infusion. In addition, six of seven subjects with refractory cancer who had completed six cycles of treatment achieved stable disease. Based on the results, phase II trials were expected to be initiated in early 2008.
October 29, 2007
Cephalon reported positive results from a phase III trial of Treanda for the treatment of non-Hodgkins lymphoma (NHL). This multicenter, single-arm study, conducted under a SPA from the FDA, enrolled 100 subjects with relapsed, rituximab-refractory NHL who were no longer responsive to treatment with rituximab. The primary endpoints, overall response rate and median duration of response, were both achieved. The overall response rate, including complete, unconfirmed complete or partial response, was reached by 75% (p<0.0001) and the median duration of response was 40 weeks (9.2 months). Treatment was determined to be safe and well tolerated. Based on the results, Cephalon plans to file a sNDA with the FDA in Q4 of 2007.
EntreMed issued positive results from a phase II trial of Panzem for the treatment of ovarian cancer. This open label trial enrolled 18 women with platinum refractory epithelial ovarian cancer who received Panzem administered as a single agent. One subject had confirmed partial response of their CA- 125, a tumor bio-marker. Five of the eighteen subjects achieved stable disease lasting greater than three months. Treatment was well tolerated, with no reports of significant neuropathy, myelosuppression or thromboembolic side effects. Two subjects remain in the study at this time. Based on the results, EntreMed plans to advance the development of Panzem for this indication.
Exelixis released positive results from an ongoing phase I trial of XL184 for the treatment of solid tumors. To date, this open-label, dose-finding trial had enrolled 33 subjects with unresectable or malignant advanced solid malignancy or lymphoma in whom alternative therapy does not exist or is ineffective. The subjects received two cycles of XL184, administered as a daily oral dose for 5 consecutive days with a 9-day observation period (0.08-11.52 mg/kg), or dosed daily (175 and 265 mg). Of seven subjects with thyroid cancer, 3 had partial responses, 6 had tumor shrinkage and 1 had non-measurable disease. All seven subjects experienced a rapid decrease in plasma levels of calcitonin and six had a decrease in the tumor marker carcinoembryonic antigen. In addition, one subject with a neuroendocrine tumor had an unconfirmed partial response. Fifteen subjects with various solid malignancies or lymphoma have had stable disease lasting from three months to up to 20 months, including nine with stable disease for more than six months. Preliminary pharmacokinetic analyses of nine dose levels (0.08-11.52 mg/kg) indicate a long half-life of 59 to 136 hours. Treatment has been well tolerated and dose escalation is continuing to determine the maximum tolerated dose. Based on positive results, Exelixis plans to commence phase II trials by the end of 2007.
Human Genome Sciences reported positive results from a phase Ib trial of lexatumumab for the treatment of cancer. This open-label, dose-escalation study enrolled 41 subjects with a variety of solid malignancies. The subjects received HGS-ETR2 (5 mg/kg or 10 mg/kg) administered intravenously, plus a full-dose regimen of chemotherapy (gemcitabine, pemetrexed, doxorubicin or FOLFIRI). Objective responses were reported for two subjects; one with colorectal cancer in the FOLFIRI arm and one with small-cell lung cancer in the doxorubicin arm. Stable disease was observed in 22 of the subjects. The pharmacokinetics of lexatumumab were not affected by the chemotherapeutic agents, nor were the pharmacokinetics of the chemotherapeutic agents affected by lexatumumab. Treatment was determined to be safe and well tolerated. Based on the results, the company plans to advance the development of lexatumumab.
October 15, 2007
Adventrx issued negative results from a phase IIb trial of CoFactor for the treatment of colorectal cancer. This open-label, randomized, controlled study enrolled 300 subjects who received CoFactor/5-fluorouracil (5-FU) or leucovorin/5- FU. The primary endpoint was a reduction in the proportion of subjects reporting at least one hematological or gastrointestinal adverse event of grade 3 or greater. The CoFactor/5-FU arm demonstrated comparable overall safety to the leucovorin/5-FU arm. However, the CoFactor/5-FU arm did not demonstrate statistically significant improved safety in the primary endpoint. In addition, no statistically significant differences were observed in overall safety and efficacy variables between the two arms. Adventrx plans to fully analyze the data in order to determine the future course of development of CoFactor for this indication.
Cell Therapeutics announced positive results from a phase I trial of brostallicin for the treatment of advanced solid tumors. This multicenter, dose-escalation trial enrolled 21 subjects who received brostallicin, escalated from 5 to 7 to 9 mg/m2 in combination with a fixed dose of cisplatin (75 mg/m2). Treatment cycles were three weeks. The primary objective was to determine any dose limiting toxicities (DLT) during the first cycle and to define the optimal dose for future studies. No DLTs occurred at the 5 or 7 mg/m2 dose, while two subjects experienced DLTs at the 9 mg/m2 dose. Hence, the optimal dose for upcoming phase II trials was determined to be brostallicin 7 mg/m2 and cisplatin 75 mg/m2 every three weeks. In addition, of the 21 treated subjects, 14 experienced disease stabilization with 7 subjects experiencing disease stabilization for more than 18 weeks. Based on the results, phase II trials are expected to commence shortly.
August 20, 2007
Cytopia reported positive preliminary results from a phase I trial of CYT997 for the treatment of cancer. This safety and efficacy trial enrolled subjects with a variety of solid tumors who had failed previous therapy or for whom no other therapy exists. The subjects received CYT997 administered as a 24-hour intravenous infusion on a three-weekly cycle, for a maximum of six cycles The primary endpoints, determination of the maximum tolerated dose (MTD) and dose limiting toxicities, were both achieved. The MTD was established at 358 mg/m2 and two reversible dose limiting toxicities were observed; a prolongation of the QTc interval and hypoxia/dyspnoea. Based on the results, Cytopia is planning to initiate phase II trials by the end of 2007.
pSivida released positive preliminary results from a phase IIa trial of BrachySil for the treatment of inoperable pancreatic cancer. This trial enrolled 17 subjects in the United Kingdom and Singapore. Subjects received BrachySil directly to a tumor in the pancreas via endoscopic ultrasound, in combination with standard chemotherapy. The primary endpoint was safety. Secondary endpoints included efficacy (reduction of tumor size) and overall survival. Eight weeks follow-up data shows treatment was well tolerated, with no reports of drug related adverse events. Efficacy data from the first 10 treated subjects shows 90% of these subjects have had either stabilization or reduction in the size of their primary tumor. Full results are expected by the end of 2007.
June 4, 2007
Alchemia released positive final results from a phase II trial of HyCAMP for the treatment of colorectal cancer. This randomized trial enrolled 80 subjects with metastatic colorectal cancer who had previously failed therapy with 5 FU. Subjects received up to eight cycles of irinotecan (Camptosar) or HyCAMP intravenously. The results concluded that when compared to the irinotecan arm, the subjects receiving HyCAMP: showed a significantly greater increase in tumor response, showed a statistically significant increase in 'time to treatment failure', had a significantly longer period (+116%) of 'progression-free survival', were able to receive therapy for a median of three times longer than those receiving Camptosar, showed a trend towards longer overall survival and received less doses of anti-diarrheal medication. Based on the results, Alchemia plans to meet with the FDA and EMEA to determine the best future course of action towards gaining approval.
Peregrine announced positive results from a phase Ib trial of bavituximab for the treatment of cancer. This open-label trial enrolled 12 subjects in India who received bavituximab given with standard chemotherapy (including docetaxel, gemcitabine and carboplatin/paclitaxel) over an eight week period. The primary endpoints were safety and tolerability as well as preliminary efficacy. Treatment was generally well tolerated, with a safety profile similar to that seen in advanced cancer patients undergoing chemotherapy alone. Objective tumor response or stable disease occurred in 50% of the subjects evaluable for tumor response. This response was greater In the subjects receiving bavituximab in combination with gemcitabine, with 75% of the subjects showing objective tumor response or stable disease. Based on the results, Peregrine plans to initiate further efficacy trials later in 2007.
February 19, 2007
Bayer and Onyx announced positive results from a phase III trial of Nexavar for the treatment of hepatocellular carcinoma. This double-blind, randomized, placebo-controlled trial, dubbed SHARP (Sorafenib HCC Assessment Randomized Protocol), enrolled 602 subjects with primary liver cancer who had not undergone prior systemic therapy. Subjects received 400 mg of oral Nexavar twice daily or matching placebo. Treatment was well tolerated with no difference in adverse events between the two treatment arms. The trial's primary endpoint was met, with the Nexavar arm resulting in superior overall survival when compared to the placebo arm. Based on these results, Bayer and Onyx stopped the trial to allow all of the subject's access to Nexavar. They plan to move forward with filing for FDA approval.
Favrille reported positive long-term results from a phase II trial of Favld for the treatment of non-Hodgkin's lymphoma (NHL). This trial enrolled 15 subjects who received Favld after high dose therapy and autologous stem cell transplantation. The first of five monthly injections of Favld was administered three months following transplantation. The trial was designed to evaluate the ability of treatment to induce humoral and cell-mediated immune responses, and to induce or maintain complete remission. Treatment was well tolerated. Data revealed that the majority of the subjects developed a rapid and tumor-specific immune response. In addition, at 61 months post-transplant, nine of the subjects remained in complete transmission. Favld is currently undergoing a second phase III trial with results expected by the end of 2007.
November 20, 2006
Kosan announced positive results from two ongoing phase I trials of KOS-1584 for the treatment of solid tumors. The first trial enrolled 37 subjects who received KOS-1584 via one-hour weekly intravenous infusion, in doses escalating from 0.8 to 25 mg/m2, every three out of four weeks. Treatment was generally well tolerated with low grade toxicities reported. Pharmacokinetic data revealed a half-life of 20-25 hours and a large volume of distribution. Antitumor activity was observed in 17% of the subjects, with one confirmed partial response and four subjects who reached stable disease over four or more cycles of treatment. The second trial enrolled 45 subjects who received KOS-1584 administered as a three-hour intravenous infusion, in doses escalating from 0.8 to 36 mg/m2, every three weeks. Treatment was well tolerated with the most common toxicities mild in nature. Antitumor activity was observed in 29.5% of the subjects, with 12 subjects reaching stable disease after 4 or more cycles of treatment. Both of these trials are ongoing in order to determine the best dose for phase II trials.
November 13, 2006
Amgen issued positive results from a phase II trial of AMG706 for the treatment of gastrointestinal stromal tumors. This trial enrolled 138 subjects who received at least one oral dose of AMG 706 at 125 mg per day until disease progression or toxicity. The primary endpoint of the trial was objective response per RECIST criteria. Secondary endpoints included an assessment of AMG706 on duration of response, progression-free survival, time to progression, survival and adverse events. The RECIST assessment showed a clinical benefit rate of 27% (3% partial response plus 24% durable stable disease greater than or equal to 22 weeks). The median progression-free survival was 16 weeks, with 26 week progression-free survival of 27%. Median survival was 59 weeks. Treatment was generally well tolerated with the most commonly reported adverse events including diarrhea, hypertension, fatigue and headache. Based on these results Amgen plans to move forward with the development of AMG706.
August 7, 2006
AEterna Zentaris and Spectrum Pharmaceuticals reported positive results of a phase II trial of ozarelix (D-63153), their luteinizing hormone releasing hormone (LHRH) antagonist for the treatment of hormone dependent prostate cancer. Trial data met their primary efficacy endpoint, establishing that cycles of 130 mg of the drug suppressed testosterone to castration-equivalent levels (< 0.5 ng/ml) for three months. In patients with castration-level suppression, serum PSA was reduced by at least 50% in 97% of subjects, compared to baseline. This open-label, randomized-controlled study enrolled 64 patients, who received one of three doses of the drug (65 mg, 100 mg 0r 130 mg) via intramuscular injection on varying 28-day dosing schedules for 3 treatment cycles. Additional results from the study were to be presented at the upcoming SIU (Societe Internationale D'Urologie) meeting in Cape Town, South Africa, on November 12, 2006.
Aida Pharmaceuticals has issued positive results of a phase I trial of Rh-Apo2L, their investigational gene therapy product for the treatment of malignant tumors. Preliminary efficacy data indicated that the drug reduced tumor size in non-Hodgkin lymphoma, sarcoma and adrenal gland cortical tumors, and affected tumor size in non-small cell lung cancer, colorectal cancer and parotid gland capsule adenocarcinoma. Treatment was generally well tolerated with no evidence of hematological toxicity observed. The study enrolled 20 patients at the Chinese Academy of Medical Sciences Oncology Hospital in Beijing, China. Based on these results, the company announced plans to apply for clearance from the SFDA to initiate phase II and III trials in the near future, with projected completion of all studies before the end of 2007.
June 12, 2006
Ariad Pharmaceuticals announced positive results of a phase II trial of AP23573, for the treatment of soft-tissue and bone sarcomas. Trial data indicated significant improvements in the trial's co-primary endpoints, clinical benefit rate (CBR; combined rate of complete response, partial response and stable disease) and duration of progression-free survival (PFS) for patients with the three most common subclasses of sarcoma. Specifically, CBR was 30% for patients with bone sarcoma; 33% for leiomyosarcoma, and 30% for liposarcomas, compared to a historical baseline of 8%; rate of PFS through 6 months (24%) and median duration of PFS (15 weeks) did not significantly differ between the 3 groups, and was superior to a historical baseline of 7 weeks. Patients with less common "other" sarcomas experienced a 6-month PFS rate comparable to the other sub-groups, though CBR was lower (23%), and below the pre-determined 25% success threshold. This multi-center study enrolled 212 patients with metastatic and/or unresectable disease, who received fixed doses of 12.5 mg AP23573 monotherapy via intravenous infusion in 4-week cycles of 5 days on/9 days off treatment.
Exelixis reported positive results of a phase I trial of XL647, for the treatment of solid tumors. Trial data yielded preliminary evidence of efficacy, with 1 partial response (NSCLC) and 12 cases of stable disease through at least 3.5 months (3 NSCLC, 2 chordoma, 2 adenoid cystic carcinoma, and 1 each adrenocortical carcinoma, colorectal, ovarian, mesothelioma, and head & neck cancer). Maximum tolerated dose was set at 4.68 mg/kg; 2 subjects administered doses higher than this level experienced dose-limiting grade 3 diarrhea. This dose-escalation study enrolled 40 subjects, who were received multiple oral doses of the drug (0.06 mg/kg to 7.0 mg/kg).
GlaxoSmithKline reported positive results of a phase III trial, dubbed EGF100151, of Tykerb, for the treatment of breast cancer. Trial data yielded significant efficacy, significantly extending time to disease progression compared to control therapy (36.9 weeks vs. 19.7 weeks; p=0.00032). Rates of treatment-related adverse events leading to discontinuation were comparable between the Tykerb (14%) and control (11%) regimens. This international, multicenter, open-label study enrolled 392 women with trastuzumab-refractory ErbB2 positive breast cancer, who received either a combination regimen of Tykerb and the approved drug capecitabine, or capecitabine alone. These results were sufficiently positive for the trial's DSMB to recommend early termination of the study in April 2006, so all patients could be transferred to the combination regimen.
ImClone announced positive results of a phase I trial of IMC-1121B, for the treatment of advanced cancers. Maximum tolerated dose had yet to be reached, with anorexia, vomiting, anemia, depression, fatigue and insomnia noted as the most frequent adverse events. These adverse events were noted as potentially distinct from those observed with other compounds designed to disrupt the VEGF system. Preliminary evidence of efficacy was also noted, with 1 partial tumor response and 5 instances of stable disease. This open-label study had enrolled 14 subjects to date, and dose-escalation was ongoing.
Pharmion and MethylGene reported interim results of a pair of phase I trials of MGCD0103, for the treatment of hematological malignancies (leukemias and myelodysplastic syndromes (MDS)), and solid tumors. Both trials were open-label, dose-escalation monotherapy studies, which had enrolled 23 and 28 patients to date, respectively. In the leukemia/MDS study, the maximum tolerated dose was somewhat below 80 mg/m2 thrice weekly, at which dose nausea, vomiting, diarrhea, and/or fatigue were dose-limiting. 3 patients (2 with acute myelogenous leukemia, 1 with MDS) achieved complete bone-marrow response. In the solid tumor trial, maximum tolerated dose had not yet been reached; the most common adverse event to date was Grade 1-3 fatigue. Stable disease was observed in 5 subjects (3 kidney cancer, 1 NSCLC and 1 colon cancer). Based on these results, the company announced plans to initiate a phase I/II trial of the drug in Q2 2006, with phase II trials to follow before year's end.
May 2, 2005
Point Therapeutics has announced results of a phase II trial of their investigational orally active irreversible dipeptidyl peptidase IV inhibitor talabostat, for the treatment of non-small cell lung cancer (NSCLC). Results from the study indicated that the drug, in combination with the chemotherapeutic docetaxel, met the study's primary endpoints of improving overall tumor response vs. docetaxel alone. This single-arm, two-stage study enrolled patients with stage IIIb/IV NSCLC whose tumors were refractory to a platinum-based first-line chemotherapy regimen. The company announced plans to present expanded results of the study at the 41st Annual Meeting of the American Society of Clinical Oncology in May, and to initiate phase III trials of the drug later in 2005.
April 25, 2005
Adventrx Pharmaceuticals reported results of a phase II trial of CoFactor (CH2FH4), in combination with 5- fluorouracil (5-FU), for the treatment of colorectal cancer. Toxicity and pharmacodynamic data indicated a positive toxicity profile based on a laboratory measures. Specifically, administration of CoFactor produced an increase producing increases in RBC folate pool expansion (form a mean baseline score of 533 ng/ml to a score of 1295 ng/ml following weekly dosing), urinary folate excretion (an indication of formaldehyde toxicity) showed a small decrease (from a baseline historical baseline of 5 ug/ml to a post-treatment mean of 3.7 ug/ml). These data support the use of CoFactor in combination with 5-FU to improve efficacy and reduce toxicity. This open-label study enrolled subjects with metastatic colorectal cancer, and was designed to investigate several laboratory measures of the toxicity associated with CoFactor administration and metabolism, in the hopes that the drug in combination with 5-FU will provide better efficacy and reduced toxicity, compared to standard therapy of 5-FU and leucovorin. The company announced that these data would serve to support upcoming phase IIb and III trials in the UK and the US.
Agennix reported positive results of a phase II trial of talactoferrin alpha in combination with chemotherapy, for the first line treatment of non-small cell lung cancer (NSCLC). Results from the study found that the addition of talactoferrin significantly improved overall response rate vs. placebo. Specifically, overall response rate in the prospectively defined evaluable patient group was 47%, vs. 29% for placebo (p= 0.05). The addition of talactoferrin was also well tolerated, with no evidence of increased toxicity. This double-blind, placebo- controlled study enrolled 110 treatment-naïve NSCLC patients, who were randomized 1:1 to receive talactoferrin or placebo, in combination with a standard chemotherapeutic regimen of carboplatin/paclitaxel.
Human Genome Sciences reported positive results of an ongoing phase I trial of their investigational TRAIL-1 monoclonal antibody HGS-ETR1, for the treatment of solid tumors. Trial data met their safety endpoints, with the highest dose acceptably tolerated and a generally mild (Grade 1 or 2) adverse event profile. Pharmacokinetics were proportional to dose, and mean elimination half-life was 17 days. Efficacy was also noted, with 10 instances of stable disease, including one subject who had received 16 treatments with the drug. This open-label, multi-center, dose- escalation trial had enrolled 44 heavily pretreated subjects to date (median prior chemotherapeutic regimens: 6), who received one of 7 IV doses of the drug (0.01, 0.03, 0.1, 0.3, 1.0, 3.0, or 10.0 mg/kg), once every 14 or 28 days.
Medarex and Bristol-Myers Squibb reported positive results of a phase II study of their investigational two-drug therapy for metastatic melanoma, which includes the anti-CTLA-4 antibody MDX-010 and the gp100 melanoma vaccine MDX-1379. Both trial dosing regimens yielded evidence of efficacy, with 2 complete responses (ongoing through 30 and 31 months) and 2 partial responses (4 months; ongoing through 34 months) in cohort 1, and 3 partial responses (6 months; ongoing through 25 and 26 months) in cohort 2. Serious Grade III/IV adverse events occurred more often in cohort 1 (n=9) than cohort 2 (n=5). This two- armed open-label study enrolled 56 subjects with metastatic melanoma, who received MDX-1379 plus 3.0 mg/kg MDX-010 every 3 weeks (cohort 1; n=29), or MDX-1379 plus an initial 3.0 mg/kg dose of MDX-010, followed by 1.0 mg/kg every 3 weeks (cohort 2; n=27).
April 18, 2005
Celgene reported positive interim results of a pair of parallel phase III trials of Revlimid (lenalidomide), for the treatment of multiple myeloma. Trial data have yielded strong evidence of superiority, with a median time to progression of at least 15 months for the US study and more than 11 months for the international study, vs. only 5 months for subjects receiving dexamethasone alone. This superiority was highly statistically significant (p<0.00001), and the duration and number of ongoing responses mean that the primary endpoint, which was to characterize the overall time to progression, cannot yet be calculated. Clinical responses were observed in 51.3% and 47.5% (respectively by trial) of subjects receiving combination therapy with the drug, vs. 22.9% and 18.4% of subjects receiving dexamethasone monotherapy (p=0.001). Both studies were randomized, double-blinded, placebo-controlled trials which enrolled relapsed or refractory multiple myeloma patients; these patients were randomized 1:1 to receive Revlimid plus dexamethasone (combination therapy) or dexamethasone alone. One trial enrolled 354 subjects across 47 US sites, while the other enrolled 351 subjects across 50 international sites. These ongoing trials are being conducted under a Special Protocol Assessment with the FDA, and will form the basis of both NDA and MAA submissions.
CureTech issued results of a phase I trial of their investigational monoclonal antibody CT-011, for the treatment of hematological malignancies. Trial data yielded positive safety indications, with no significant adverse events noted and a positive overall toxicity profile: no dose-limiting toxicities were observed, the most common adverse events were mild allergic reaction and low grade fever, and single-administration maximum tolerated dose was not reached. Preliminary evidence of clinical response was also observed in 5 subjects, with 1 partial response (including platelet transfusion independence) through 8 months, 2 incidences of stable disease through at least 7 months, and 2 minimal responses. This open-label escalating dose study enrolled 17 subjects with advanced refractory hematological malignancies at the Chaim Sheba Medical Center in Tel-Hashomer, Israel. Subjects received a single 5-hour intravenous infusion of escalating doses of the drug, and were followed for safety, tolerability, and evidence of disease progression.
Lorus Therapeutics has reported preliminary results of a phase II study of GTI-2040, their investigational ribonucleotide reductase R2 inhibitor, for the treatment of renal cell carcinoma. Results from the study yielded evidence of efficacy, with 52% of subjects experiencing disease stabilization or better, including 1 patient with a 23% reduction in tumor burden and disease stabilization through 10 months and 1 partial response, a 39% reduction in tumor burden and disease stabilization through 8 months. This open-label study enrolled 33 patients with advanced metastatic renal cell carcinoma across 7 US sites, who received combination therapy with GTI-2040 and capecitabine, an approved chemotherapeutic. The trial was co-sponsored by the National Cancer Institute.
April 4, 2005
Viventia Biotech reported positive preliminary results from a phase I investigating Proxinium, a monoclonal antibody conjugated to a cytotoxic protein payload for the monotherapy treatment of refractory head and neck cancer. Efficacy results showed that 25% of the 16 patients who expressed the therapeutic target for Proxinium had a complete response to therapy, which was defined as a complete disappearance of the tumor. Data showed that 63% of subjects had an objective response, defined as significant or partial shrinkage of the tumor; and 88% had tumor growth control, defined as an objective response or stabilization of disease. The drug was shown to have a good safety profile and was well tolerated. The study enrolled 20 subjects who had failed previous courses of surgery, chemotherapy and/or radiotherapy. The patients received the drug by direct intratumoral injection directly into a target tumor on a weekly basis for four weeks. The study was conducted in Brazil. The company plans to report full results at the American Society of Clinical Oncology (ASCO) Annual Meeting in May 2005.<
March 22, 2004
AVI BioPharma reported positive results from a clinical trial investigating AVI-4557, an oral Neugene antisense drug. Results showed that administration of AVI-4557 lowered midazolam levels by 700 ml/min from a baseline of 877 ml/min. Maximal blood concentration (Cmax) increased from 51 ng/ml pre-dose to 81 ng/ml post-dose. The study was designed to investigate AVI-4557 ability to inhibit expression of CYP and alter the pharmacokinetics of midazolam, an anesthetic drug metabolized by CYP. The study evaluated a 10mg midazolam dose, followed by five daily oral doses of AVI-4557. The primary endpoint was a reduced rate of midazolam metabolism as demonstrated by a decrease in midazolam clearance and an increase in midazolam (Cmax).
October 27, 2003
Astrazeneca reported final results from a pivotal phase II trial investigating Iressa (gefitinib), an approved drug for the treatment of non-small cell lung cancer. Results showed that 12% of subjects who received Iressa (250 mg),once daily, demonstrated at least a 50% reduction in tumor size. Further analysis showed a tumor response rate of 13.6% at the recommended dose of 250 mg and 10.6% overall for both doses tested. The median duration of response was 7 months. The double-blind, randomized study enrolled 216 subjects who had previously received two or more types of chemotherapy. Iressa is approved in the U.S. for use as monotherapy for the treatment of advanced non-small cell lung cancer after failure of both platinum-based and docetaxel chemotherapy. Results were reported in October 2003 in The Journal of the American Medical Association.
GlycoGenesys reported positive results from a phase I trial investigating GSC-100, a Galectin-3 targeting agent for the treatment of various cancers. Results showed that five (41.7%) subjects achieved stable disease for at least three months. One subject still remains on GCS-100 after 18 months of treatment and has achieved a partial response. GCS-100 was well tolerated with no dose-limiting toxicity observed. A maximally tolerated dose was not reached at dose levels up to 80 mg/m2. The open-label, dose escalation study enrolled 12 subjects and was designed to test the drug on subjects with unresectable, relapsed, or refractory advanced solid tumors for which there is no curative therapy. GCS-100 was administered intravenously, twice weekly, at doses of 30, 42.5, 60 or 80 mg/m2 for up to six, four-week treatment cycles, or six months.
June 9, 2003
Agennix and Veterans Affairs Medical Center reported positive results from two phase I/II trials investigating Lactoferrin (rhLF), a natural protein found in milk, for the treatment of solid tumors. Data showed that 53% of evaluable subjects (10 /19) demonstrated stable disease, three of which showed tumor shrinkage. In addition, 29 subjects completed dosing, with only one withdraw due to disease progression. The saftey portion of the studies enrolled 30 subjects and evaluated rhLF as a single agent for the treatment of solid non-resectable tumor cancer patients, who had progressed on standard chemotherapy. Subjects were administered one of four different doses of rhLF, (1.5g to 9g), either for 14 days or in cycles of 14 days. The drug was well tolerated with no drug-related serious adverse events reported.
February 10, 2003
Aphton reported positive interim results from a phase II trial investigating G17DT, an anti-gastrin immunogen for the treatment of gastric cancers. Interim results showed an overall response rate of 51%, with 37 subjects achieving a partial or complete tumor response. An additional 23 subjects achieved stable disease. One subject responded to the treatment with a 70% reduction in tumor size and disease stabilization 7 to 8 months after therapy. After the sixth treatment the subject achieved a complete response. The randomized study enrolled 103 subjects (73 evaluable) with metastatic stomach cancer who were treated with G17DT plus chemotherapy and 5FU.
Exelixis reported positive preliminary results from a phase II trial investigating DEAE-Rebeccamycin, an anticancer compound for the treatment of bile duct tumors. Data revealed that the drug was safe and may result in tumor shrinkage. Early results included two partial responses and 7 disease stabilizations, a 45% non-progression rate. Adverse events included transient and reversible myelosuppression. Nine subjects had survived upon a 12.5-month median follow-up. The results were compiled from a cohort of 20 subjects with advanced unresectable bile duct cancers. Subjects were given a 165 mg dose of rebeccamycin analogue daily for five days every three weeks. Exelixis and the NCI are collaborating on the development of rebeccamycin.
February 3, 2003
Amgen reported positive results from a phase III trial investigating rHu-KGF, a natural keratinocyte growth factor for the treatment of oral mucositis as a complication of cancer treatments. Preliminary results from the randomized, double blind trial were positive on all endpoints showing a highly significant decrease in both the duration and incidence of severe mucositis. In addition, results showed that the drug was well tolerated. The study enrolled subjects who underwent bone marrow transplantation treatment for hematologic malignancies such as lymphoma, multiple myeloma, and leukemia.
January 21, 2003
ImmunoGen reported results of a phase I dose-escalation study of HuC242-DM1/SB-408075 (cantuzumab mertansine) in subjects with refractory cancer that expresses the CanAg antigen. Dosing was increased in each new cohort of subjects until dose-limiting toxicity was demonstrated. Based on the results, the recommended dose for cantuzumab mertansine is 235 mg/m2 when administered once every three weeks. In addition, one subject with colon cancer exhibited DM1 localization at the tumor site 24 hours after administration of the drug. Furthermore, this subject had a reduction in lung metastases after two and four courses of cantuzumab mertansine
Introgen reported positive results from a phase II trial investigating Advexin (p53 therapy) for the treatment of non-small cell lung cancer. Results showed that approximately 60% of subjects' primary tumors regressed or disappeared, as assessed by both biopsies and by CT scans three months after treatment. Administration of the drug did not appear to increase the side effect caused by radiation treatment. The study enrolled subjects with non-metastatic non-small cell lung cancer who were ineligible to receive alternative treatments. Advexin was administered via injection into tumors at a range of doses over one month.
Rational Therapeutics reported positive results from two phase II trials investigating gemcitabine with cisplatin as a combination therapy in the treatment of relapsed ovarian cancer. In the first study, results showed that the combination therapy achieved a 70% response rate, with more than 20% of subjects achieving complete remission. Subjects who demonstrated the most tumor response also showed the most sensitivity to the drug in ex-vivo laboratory assays. Out of 27 subjects, there were 26% (7) complete and 44% (12) partial responses. Subjects received cisplatin (30 mg/m2) plus gemcitabine (600-750 mg/m2) intravenously. Seventeen subjects underwent ex vivo analyses for correlation with clinical response. The second study enrolled 36 platinum and paclitaxel resistant subjects. Of the 15 subjects that responded, 11 were partial clinical responses and 4 were complete clinical responses. Gemcitabine (750 mg/m2) was administered intravenously over 30 min followed by cisplatin (30 mg/m2).
January 6, 2003
Isis Pharmaceuticals reported positive results from a phase II trial investigating ISIS 2503 in combination with gemcitabine for the treatment of pancreatic cancer. Results showed 57.5% of subjects who received ISIS 2503, in combination with gemcitabine, survived six months or longer with a median survival time for those 20 subjects of 6.7 months. This was compared to historical gemcitabine pivotal trial results of 46% at six months survival with a median survival time of 5.6 months. The open-label Phase II trial enrolled 48 subjects with locally advanced or metastatic pancreatic cancer who had not received prior chemotherapy for their disease.
Neurocrine Biosciences reported positive results from two trials investigating IL-4 Fusion Toxin (NBI-3001) for the treatment of glioblastoma multiforme and solid tumors. Preliminary data from an ongoing phase I trial conducted in subjects with peripheral solid tumors showed the study has met the primary objectives of defining dose toxicity and tolerance. Two subjects with kidney carcinoma showed stable disease at the maximum tolerated dose. Data from a phase II trial conducted on subjects with glioblastoma multiforme (GBM) showed a median survival greater than six months at low dosage (90 mcg) with the majority of the subjects still alive at time of follow up. MRI scans showed 25% of the subjects reached stable or partial regression of disease. The open label study enrolled 32 subjects with recurrent GBM and infused them intramorally at high, medium and low doses over five days.
December 16, 2002
SuperGen reported positive results from more than 12 trials investigating Nipent for the treatment of multiple cancers. A phase II trial using Nipent in combination with Rituximab for the treatment of chronic lymphocytic leukemia (CLL) demonstrated that 33% of subjects achieved an objective response. Stable disease was observed in 54% of subjects with a median response of 9.8 months. A phase I trial using Nipent for the treatment of steroid refractory acute graft-versus-host disease enrolled 23 subjects with a variety of hematological malignancies. Results showed 11 subjects achieved complete responses and 6 achieved partial or mixed responses. A long term follow-up study of Nipent in 180 subjects with hairy cell leukemia demonstrated a response rate of 98%. Data showed that 83% of subjects achieved a complete response and 15% achieved a partial response.
Titan Pharmaceuticals reported mixed results from a phase III trial investigating CeaVac, a monoclonal antibody for the treatment of metastatic colorectal cancer. CeaVac failed to demonstrate a statistically significant improvement in the primary endpoint of survival in the overall efficacy, but a trend toward 2-3 month survival improvement was shown in subjects receiving at least 5 doses. The randomized, placebo-controlled study enrolled 631 subjects receiving chemotherapy with 5- flourouracil (5-FU) and leucovorin for metastatic colorectal cancer. Subjects in the study received injections of CeaVac once every two weeks for 2 months and then once per month after. Treatment with CeaVac was generally well tolerated, with the most common side effect being local injection site irritation.
December 2, 2002
Cell Therapeutics reported positive results from a series of clinical trials investigating Trisenox (arsenic trioxide) and concluded that the drug may be effective in inducing high rates of remission in hematologic malignancies like myelodysplasia (MDS) and chronic myeloid leukemia (CML). In the study, 29 subjects with newly diagnosed CML, 19 subjects (66 %) achieved complete remission with four subjects achieving partial remission for an overall response rate of 79 %. In 21 subjects with MDS-refractory anemia (MDS-RA), six subjects (29 %) achieved a complete remission and eight subjects (38 %) achieved a partial remission for an overall objective response rate of 67 %. In 18 subjects with MDS-refractory anemia with excess blasts (MDS-RAEB), three achieved stable disease or better.
Kosan Biosciences and Roche reported positive interim results from a phase I trial investigating KOS-862 (Epothilone D), a polyketide natural product similar to paclitaxel for the treatment of advanced solid tumors. The study is determining possible drug-related toxicities, pharmacokinetics, and pharmacodynamics of escalating intravenous doses of KOS-862 administered every 3 weeks. Pharmacokinetics are linear and the drug shows a 10-hour half-life with good tissue penetration. The pharmacodynamic measurements demonstrate that maximal microtubule bundle formation in peripheral blood cells correlates with maximal plasma concentrations. To date, KOS-862 has been evaluated in 42 subjects with results showing no myelosuppression.
November 25, 2002
GenVec reported positive results from a phase Ib trial investigating TNFerade for the treatment of cancer. The study was designed to test the safety and efficacy of TNFerade in 63 subjects with a wide variety of cancers. The data showed 73% of subjects showed objective tumor shrinkage, their tumors shrank between 25% and 100%, with TNFerade therapy. The objective tumor responses were shown to be: Complete Response (CR) 16.6% of subjects, Partial Response (PR) 30% of subjects and Minor Response (MR) 26% of subjects. Among the subjects with pancreatic cancer, 75% showed tumor shrinkage and one subject showed no disease progression after 18 months. TNFerade was well tolerated and side effects were all classified as mild.
Maxim Pharmaceuticals reported positive results from a phase II trial investigating Ceplene (histamine dihydrochloride) with interleukin-2 (Il-2) for the treatment of advanced metastatic melanoma. The treatment significantly increased the expression of CD3 zeta in T cells and Natural Killer (NK) cells. Treatment with Ceplene and IL-2 also resulted in a decrease in the production of IL-6, a pro-inflammatory cytokine associated with the down-regulation of T cells and NK cells. The study, which enrolled a total of 50 subjects, was designed to investigate the effect of Ceplene and IL-2 on the expression of specific cellular markers that may be associated with the function of key immune cells.
November 4, 2002
PRIMABioMed reported positive preliminary results of a phase I trial investigating their dendritic cell based therapy as a cancer treatment. The therapy recognizes a cancer protein that is highly expressed in breast, ovarian, lung and prostate cancers and so is able to stimulate a specific immune response. The study consisted of 10 subjects with various cancers, treated with three doses of therapy, over a 12-week period. Data demonstrated the therapy was safe and was able to produce the specific immunological response. The study was conducted at the Austin Research Institute (ARI) and the Austin & Repatriation Medical Centre in Melbourne, Australia.
October 21, 2002
Novartis reported positive results from a study to examine the long-term efficacy of Zometa. Novartis submitted the data along with its sNDA for the indication of bone metastases developed from advanced cancers. The data was analyzed from three large multi-center, randomized pivotal trials of more than 3,000 patients The trials demonstrate that the benefits of Zometa were maintained over the approximately two years of treatment follow-up. In addition, breast cancer patients treated with Zometa 4 mg had a significantly lower risk of developing skeletal complications after two years of treatment, compared with those treated with pamidronate 90 mg.
April 8, 2002
Phase I trial results for Oncolytics Biotech's Reolysin, a potential cancer therapeutic for Ras activated tumors, indicate that the drug is generally well tolerated. The trial evaluated escalating dosages of Reolysin administered directly into a subcutaneous tumor in 18 terminal cancer subjects with progressive cancer that had failed to respond to conventional therapies. None of the subjects receiving Reolysin experienced any serious adverse events related to the virus, and no dose-limiting toxicities were detected. Evidence of viral activity, which was defined as transitory or lasting tumor regression of at least 30%, was detected in 11 of 18 patients (61%), with regression ranging from 32% to 100%.