Non-Small Cell Lung Cancer
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.
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 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).
October 20, 2014
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
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.
September 2, 2013
Eli Lilly released results of a phase III trial of necitumumab (IMC-11F8) in combination with gemcitabine and cisplatin as a first-line treatment, as compared to chemotherapy alone, for the treatment of with stage IV metastatic squamous non-small cell lung cancer (NSCLC). The trial enrolled 1093 patients (age greater than or equal to 18 years, ECOG PS 0-2) with histologically- or cytologicallyconfirmed, stage IV squamous NSCLC, who had received no prior therapy for metastatic disease. Patients underwent radiographic assessment of disease status (computed tomography or magnetic resonance imaging) every six weeks (+/- 3 days), until radiographic documentation of progressive disease (PD). The most common adverse events occurring more frequently in patients on the necitumumab arm were rash and hypomagnesemia. Serious, but less frequent, adverse events occurring more often on the necitumumab arm included thromboembolism. Lilly plans to present results from this study at a scientific meeting in 2014, and currently anticipates submitting to regulatory authorities before the end of 2014.
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.
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 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.
March 4, 2013
Peregrine Pharmaceuticals issued results from a phase II trial of bavituximab for the treatment of non-small cell lung cancer (NSCLC). This Peregrine's randomized, double-blind, placebo-controlled study enrolled 121 patients with previously treated locally advanced or metastatic second-line NSCLC. Subjects received bavituximab 3mg/kg plus docetaxel or placebo plus docetaxel. Results showed a meaningful improvement in median overall survival of 11.7 months in the bavituximab plus docetaxel arm compared to 7.3 months in the control arm (HR=0.73; p value=0.217). Persistent separation in the survival curves was observed with response rates and progression-free survival also favoring the bavituximab plus docetaxel. Bavituximab was well tolerated. The most frequent adverse events were similar between both treatment arms. Based on these data, Peregrine is preparing for an end-of-phase II meeting with the FDA.
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.
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
Boehringer Ingelheim issued results from a phase III trial of afatinib as a first-line treatment for stage IIIb or IV non-small cell lung cancer (NSCLC). This randomized, open-label, comparative study, LUX-Lung 3, enrolled 345 patients with NSCLC harboring an epidermal growth factor receptor (EGFR) mutation. Subjects received afatinib (n≡230) or pemetrexed/cisplatin (n≡115). The study met its primary endpoint of progression-free survival (PFS). In the general population, afatinib-dosed subjects averaged an 11.1 month PFS versus 6.9 months PFS for subjects dosed with pemetrexed/cisplatin. The hazard ratio was 0.58 (95% CI: 0.43-0.78) (p≡0.0004). In the sub-population of patients with the most common EGFR mutations (Del19 and L858R), afatinib-dosed subjects had a PFS of 13.6 months versus 6.9 months in the chemotherapy arm. The hazard ratio in this patient subset was 0.47 (95% CI: 0.34-0.65) (p<0.0001). The most common adverse events were diarrhea, rash and paronychia.
December 12, 2011
Peregrine Pharmaceuticals reported preliminary results from a phase II trial of bavituximab for non-small cell lung cancer. This randomized trial enrolled 86 subjects with front-line, Stage IV metastatic NSCLC. The subjects received bavituximab (3 mg/kg) or placebo weekly, each in combination with paclitaxel (200 mg/m2) and carboplatin (AUC 6), administered on day one of each 21-day cycle, for up to six cycles. Results showed a 50% improvement in overall tumor response rates. Subjects treated with bavituximab plus carboplatin and paclitaxel demonstrated an overall response rate of 39%, versus 26% in subjects treated with carboplatin and paclitaxel alone.
July 11, 2011
Oncolytics Biotech reported interim results from a phase II trial of Reolysin for non-small cell lung cancer (NSCLC). This open label trial has enrolled 22 subjects with Kras or EGFR-activated metastatic tumors, including adenocarcinoma), squamous cell carcinoma and bronchioloalveolar carcinoma. The subjects received Reolysin (3 x 1010 TCID50) intravenously daily on days one to five, in combination with carboplatin and paclitaxel. Response evaluation to date in 21 subjects showed six partial responses (28.6%), 13 subjects with stable disease (61.9%) and two with progressive disease (9.5%), for a clinical benefit rate of 90.5% and a response rate of 28.6%.
June 13, 2011
Pfizer released results from a phase I trial of crizotinib for the treatment of ALK-positive non-small cell lung cancer (NSCLC). Data are from 82 ALK+ subjects. The data was compared to phase I historical controls from 37 NSCLC ALK+ subjects who were not treated with crizotinib (ALK+ controls), as well as 253 NSCLC ALK-/EGFR- subjects (ALK- controls). In the 82 ALK+ subjects treated with crizotinib, the one year overall survival was 77% and two year overall survival was 64%. The median overall survival has not been reached. Among the ALK+ controls, the one- and two-year overall survival was 73% and 33%, respectively, and median overall survival was 20 months. Subsets of ALK+ subjects were also evaluated by line of therapy. Survival of 32 subjects treated with second or third line crizotinib was significantly longer than that of 24 ALK+ controls (p≡0.004): one-year overall survival was 71% versus 46%, two-year overall survival was 61% versus 9%. For 123 ALK- controls in the 2nd line setting, the one and two-year overall survival was 49% and 33%, respectively.
June 6, 2011
AVEO Pharmaceuticals reported interim results from an ongoing phase Ib/II trial of ficlatuzumab for non-small cell lung cancer (NSCLC). This trial was designed to evaluate the combination of ficlatuzumab plus gefitinib (Iressa) for the first-line treatment of NSCLC in an Asian population. The phase Ib dose escalation portion enrolled 15 subjects; the first cohort (n≡3) received 10 mg/kg and the second cohort (n≡12) received 20 mg/kg intravenously every two weeks, both in combination with gefitinib 250 mg once-daily, oral for full four week cycle. No dose limiting toxicities were observed and the recommended phase II dose was ficlatuzumab 20 mg/kg intravenously every two weeks combined with gefitinib 250 mg once-daily, orally. Out of the 12 subjects in the second cohort, five (all of whom had no prior EGFR TKI therapy) experienced a partial response and four experienced stable disease.
August 2, 2010
Allos Therapeutics issued positive results from a phase IIb trial of Folotyn for the treatment of advanced non-small cell lung cancer. This enrolled 201 current or former smokers with Stage IIIB/IV disease who had received one or two previous treatment. The first 35 subjects enrolled in the study were randomized to receive Folotyn (intravenous push on days 1 and 15 of a 28-day cycle; initial dose of 230 mg/m2) or erlotinib (oral, 150 mg daily in a 28-day cycle). Subsequently, following a protocol amendment, 166 subjects were randomized to receive either Folotyn at 190 mg/m2 or erlotinib at 150 mg/day. The primary endpoint was a comparison of overall survival between the two treatment arms. The full analysis set included all 201 subjects and the primary efficacy analysis included the 166 patients enrolled subsequent to the protocol amendment. The subjects receiving Folotyn had a 16% reduction in the risk of death compared to erlotinib in the overall population and a 13 % reduction in the risk of death in the primary efficacy analysis population.
April 12, 2010
ArQule released positive results from a phase II trial of ARQ197 for the treatment of non-small cell lung cancer. This randomized, double-blind trial enrolled 167 EGFR (epidermal growth factor receptor) inhibitor nave subjects who were randomized to receive either the combination of ARQ 197 plus erlotinib or placebo plus erlotinib in second and third line settings. The primary endpoint was improvement in median progression-free survival (PFS). The median PFS was 16.1 weeks in the ARQ 197 plus erlotinib arm, compared with 9.7 weeks in the erlotinib plus placebo arm. This improvement was more pronounced in the pre-defined sub-group of patients with non-squamous histology (n≡117). Median PFS was 18.9 weeks in the active treatment arm versus 9.7 weeks in the control arm, representing a 94% improvement.
March 22, 2010
Abraxis reported positive preliminary results from a phase III trial of Abraxane for the first-line treatment of non-small cell lung cancer (NSCLC). This international trial enrolled 1,052 subjects with advanced disease who were placed in one of two treatment arms: Arm A received Abraxane 100 mg/m2 weekly plus carboplatin AUC 6 and Arm B received Taxol 200 mg/m2 weekly plus carboplatin AUC 6. Both arms receive treatment on Day One of a three-week treatment cycle. The primary study endpoint was disease response, measured as complete and partial responses as defined by RECIST. Preliminary data showed that Abraxane resulted in a significant improvement in overall response rate as compared to Taxol.
March 30, 2009
Endocyte reported positive interim results from a phase II trial of EC145 for the treatment of advanced non-small cell lung cancer. This single-arm, open label trial planned to enroll 41 subjects in the US. During the induction phase the subjects received EC145 as a 1.0 mg intravenous injection, Monday through Friday, for the first three weeks of each four week cycle. During the maintenance phase the subjects received EC145 as a 2.5 mg intravenous injection, Monday, Wednesday, and Friday on weeks one and three of each four week cycle. The primary endpoint was disease progression. At the planned interim analysis, 35% of subjects achieved clinical benefit (complete response + partial response + stable disease). In addition, 67% of subjects had duration of response of six months or longer, and one subject had significant tumor reduction of greater than 30%.
November 10, 2008
YM Biosciences released positive results from two phase II trials of nimotuzumab for the treatment of brain metastases and brain cancer. The first trial was a randomized, open, controlled trial in 30 subjects diagnosed with advanced non-small cell lung cancer (NSCLC) and unresectable brain metastases. The subjects received nimotuzumab (200 mg administered as weekly intravenous infusions over weeks 1-6) plus palliative radiation (40 Gy in four weeks) or palliative radiation alone. The primary endpoint was disease control rate (DCR- Complete Response + Partial Response + Stable Disease). Data are from the first 21 subjects. DCR was 91.6% for the nimotuzumab plus radiation arm compared to 44.4% for the radiation alone arm. Subjects treated with the combination had a median survival of 7 months compared to the control group for whom the median survival was 2.47 months (p= 0.0039). The second trial was a randomized, double blind phase II/III trial in 80 subjects with newly diagnosed high-grade glioma. Following biopsy, partial or total resection of the tumor, the subjects received six weekly infusions of placebo or nimotuzumab (200 mg) while also receiving radiotherapy, followed by a maintenance dose of nimotuzumab or placebo every 21 days. The treatment duration was one year. Results are from the first 65 enrolled subjects. The median survival time for the subjects treated with nimotuzumab plus radiotherapy was 16.43 months, while the median survival time for the placebo arm was 10.49 months. Nimotuzumab was well tolerated in both studies.
May 5, 2008
Boehringer Ingelheim released positive results from a phase II trial of BIBF 1120 for the treatment of non-small cell lung cancer. This double blind, randomized study enrolled 73 subjects with advanced and metastatic NSCLC who had received at least one platinum-based therapy, and had an ECOG score of 02. The subjects received BIBF-1120 administered twice daily (150 mg or 250 mg). The primary endpoints were progression-free survival (PFS) and objective tumor response. Secondary endpoints included overall survival (OS) and safety. BIBF 1120 showed a substantial clinical effect in a subset of 57 subjects with ECOG scores of 0 or 1. The data showed that the median OS and PFS of this group were 9.5 and 2.9 months, respectively, compared with 5.5 and 1.7 months in the overall study population. This subset also had a higher stable disease rate of 59%, compared with the overall study population. Disease control was achieved in 48% of subjects and no difference in efficacy between the two dose treatment arms was observed. The 250 x 2 mg dose, with the option of reduction to 150 x 2 mg, was considered the recommended dose for monotherapy. BIBF 1120 was well tolerated, with the most frequent adverse events including mild-to-moderate nausea, diarrhea and vomiting. Based on the results Boehringer Ingelheim plans to move forward with the development of BIBF 1120.
January 21, 2008
Transgene issued positive preliminary results from a phase IIb trial of TG4010 for the treatment of non-small cell lung cancer (NSCLS). This randomized, open label and controlled study enrolled one hundred and forty eight subjects across France, Poland, Germany, and Hungary. All subjects had NSCLC expressing MUC1, either stage IIIB with effusion or stage IV, and had not received prior systemic treatment. The trial was designed to compare TG4010 in combination with cisplatin and gemcitabine chemotherapy to the chemotherapy regimen alone. Half the subjects received the combination regimen and the other half received chemotherapy alone. The combination treatment was well tolerated, with most adverse events considered related to chemotherapy. Hematological toxicity was equivalent in both treatment groups. Full results from this ongoing trial are expected in the fourth quarter of 2008.
November 5, 2007
Cougar Biotechnology issued positive results from a phase I trial of CB7630 for the treatment of prostate cancer. This dose-ranging trial enrolled twenty-seven subjects with chemotherapy-nave, castration refractory prostate cancer (CRPC). Eighteen subjects received once daily doses of CB7630 on an empty stomach and nine received CB7630 on a full stomach (with a high fat calorie meal). Overall, of the twenty-seven subjects, sixteen (59%) experienced a greater than 50% decline in prostate specific antigen (PSA) levels. Furthermore, eleven of the eighteen subjects (61%) in the fasted group and five of the nine subjects (56%) in the fed group experienced a greater than 50% decline in PSA levels. Treatment with CB7630 was found to be well tolerated in both groups and the safety profile was unaffected by administration of the drug with food. Based on the results, Cougar plans to continue with the development of CB7630.Cougar Biotechnology issued positive results from a phase I trial of CB7630 for the treatment of prostate cancer. This dose-ranging trial enrolled twenty-seven subjects with chemotherapy-nave, castration refractory prostate cancer (CRPC). Eighteen subjects received once daily doses of CB7630 on an empty stomach and nine received CB7630 on a full stomach (with a high fat calorie meal). Overall, of the twenty-seven subjects, sixteen (59%) experienced a greater than 50% decline in prostate specific antigen (PSA) levels. Furthermore, eleven of the eighteen subjects (61%) in the fasted group and five of the nine subjects (56%) in the fed group experienced a greater than 50% decline in PSA levels. Treatment with CB7630 was found to be well tolerated in both groups and the safety profile was unaffected by administration of the drug with food. Based on the results, Cougar plans to continue with the development of CB7630.
GenVec reported positive interim results from a phase II trial of TNFerade for the treatment of colorectal cancer. This trial enrolled seven subjects who received TNFerade administered weekly via intratumoral injections during the first five weeks of radiotherapy. All subjects also received oral capecitabine twice daily during radiotherapy. Surgical removal if the tumor was performed six to nine weeks following therapy. Prior to treatment, four of the seven subjects were classified as highly likely to need sphincter removing surgery with colostomy. Following treatment with TNFerade, all seven subjects who underwent surgical resection had successful sphincter sparing procedures. In addition, five of the seven subjects showed complete response. Based on the data, GenVec plans to continue the development of TNFerade for this indication.
Infinity and MedImmune released positive preliminary results from a phase I/II trial of IPI-504 for the treatment of non-small cell lung cancer. In the phase I portion of this open label trial, 12 subjects who received IPI-504 at three dose levels (150, 225, and 300 mg/m2) on a four-week cycle, consisting of twice-weekly dose administration with no break in treatment. Of the 12 subjects, 9 were evaluable for response. Stable disease, as measured via RECIST (Response Evaluation Criteria in Solid Tumors), was achieved over at least one cycle of administration in 7 subjects, one of whom experienced extended stable disease over seven cycles (twenty-seven weeks). In addition, four subjects underwent PET imaging. All four showed a decrease in tumor metabolic activity in response to IPI-504 administration, as measured by uptake of 18-fluorodeoxyglucose. Treatment was well tolerated at doses up to 225 mg/m2. The phase II portion is expected to begin by the end of 2007.
Pharmion and GPC Biotech issued negative results form a phase III trial of satraplatin for the treatment of prostate cancer. This double-blinded, randomized, placebo controlled trial enrolled 950 subjects with hormone-refractory prostate cancer. The trial was designed to compare satraplatin plus prednisone or placebo plus prednisone as a second-line treatment for prostate cancer. The primary endpoint of overall survival was not achieved (p=0.80, stratified log rank analysis). The median overall survival was 61.3 weeks for the satraplatin arm compared to 61.4 weeks for the control group and the hazard ratio was 0.97 (95% CI: 0.83, 1.13). The companies plan to fully evaluate the data in order to determine future development plans.
September 24, 2007
Exelexis announced positive interim results from a phase II trial of XL647 for the treatment of non-small cell lung cancer (NSCLC). Reported data is from 30 evaluable subjects with stage IIIB or IV NSCLC who received XL647 administered orally, at a dose of 350 mg on days 1-5 of repeated 14-day cycles. To date 8 partial responses and 11 stable disease had been reported. Of the 8 subjects who experienced partial responses, 4 had epidermal growth factor receptor (EGFR) exon 19 deletions, 1 had an EGFR L858R mutation, and 3 were EGFR wild-type. All 6 subjects with EGFR-activating mutations demonstrated clinical benefit, with 5 partial response and 1 stable disease. Treatment was generally well tolerated. Additional phase II trials are currently underway.
Kosan issued positive results from a phase I trial of alvespimycin for the treatment of breast and ovarian cancer. This trial enrolled 25 subjects who received one-hour weekly intravenous infusion of 60, 80 or 100 mg/m2 alvespimycin administered along with the standard dose of trastuzumab. The subjects were assessed every four weeks for toxicity and every eight weeks for response, as measured by RECIST criteria and tumor markers. Clinical benefit was observed in 42% of evaluable subjects with HER2-positive metastatic breast cancer. This included one subject with complete resolution of lung metastases, one subject with a 10% reduction in tumor mass and tumor necrosis, one subject with a partial response after 2 cycles and five subjects with stable disease. Of the subjects with ovarian cancer, there was one subject with a near complete resolution of ascites and left pleural effusion at the end of cycle 2. Based on the results, Kosan plans to expand the phase I trial to add weekly dosing with paclitaxel. Phase II trials are planned for Q4 of 2007.
Merck reported positive long-term results from a phase II trial of Stimuvax for the treatment of non-small cell lung cancer (NSCLC). This study enrolled 171 subjects with stage IIIB/IV nsclc with stable or responding disease after any first-line chemotherapy with or without radiotherapy. The subjects were stratified by disease stage than randomized to receive Stimuvax plus best supportive care (BSC) or BSC alone. The subjects in the Stimuvax arm received a single intravenous dose of cyclophosphamide 300mg/m2 followed by 8 weekly subcutaneous immunizations with Stimuvax (1,000 mg). Although the overall study results did not reach statistical significance, the subjects with stage IIIB cancer receiving Stimuvax showed a median survival of 30.6 months versus 13.3 months in the control group. At the three year follow-up, 49% of the subjects who were treated with Stimuvax were still alive versus 27% treated with BSC alone, representing a 45% reduction in mortality. Based on the results, Merck is currently conducting a phase III trial of Stimuvax for the treatment of stage IIIA or IIIB non-small cell lung cancer.
Pfizer released positive preliminary results from a phase II trial of sunitinib for the treatment of non-small cell lung cancer (NSCLC). The trial was designed to compare sunitinib (37.5 mg/day) in combination with erlotinib (150 mg/day) in previously treated subjects with advanced NSCLC. The primary endpoint was safety and tolerability. Secondary endpoints included anti-tumor activity. The combination treatment was generally safe and well tolerated, with all adverse events mild to moderate in nature. Two subjects had partial response; one which was maintained for >3 months and one which was currently ongoing. In addition, stable disease up to or more than 16 weeks was observed in two subjects. The randomized portion of this trial is currently underway.
YM BioSciences announced positive preliminary results from a phase I/II trial of nimotuzumab for the treatment of non-small cell lung cancer (nsclc). This trial had enrolled 13 subjects to date in Canada. The subjects received nimotuzumab at three dose levels (100 mg, 200 mg and 400 mg weekly) with palliative radiation. Of the six subjects enrolled in the first cohort (100 mg), four partial response (PR) and two stable disease (SD) were reported. Median Overall Survival was 41.5 weeks. Of the seven subjects in the second cohort (200 mg) two PR and five SD were reported. Median Overall Survival in this group had not been reached but exceeded 25 weeks at this time. Treatment was generally well tolerated in both arms. Enrollment in the third cohort is underway, with accrual anticipated to be completed by the end of 2007. These results will be used to determine the optimal dose for the randomized phase II portion of the study.
September 17, 2007
Ardana announced positive preliminary results from a phase II trial of teverelix for the treatment of prostate cancer. This 8-week randomized trial enrolled 38 subjects who received either low dose or high dose teverelix. The primary endpoint was duration of testosterone suppression to below castration level (< 0.5 ng/ml). Secondary endpoints included the percentage of subjects attaining and maintaining medical castration, an evaluation of prostate specific antigen (PSA) and luteinizing hormone levels, and local and systemic tolerability of the drug. By day three, testosterone suppression was attained in 14 and 18 subjects in the low- and high-dose groups, respectively. A total of 19 high-dose-treated subjects had a reduction of testosterone levels to castration level, the duration of which was between 54 to 147 days, with 17 subjects being castrated for 8 weeks or more. In addition, at week 4 normalized PSA (< 4.0 ng/ml) levels were observed in 74% of the high dose group and mean PSA levels were normalized at 8 weeks. Based on the results, Ardana plans to advance the development of teverelix.
AstraZeneca released positive results from a phase III trial of Iressa for the treatment of non-small cell lung cancer (nsclc). This trial was dubbed INTEREST (IRESSA Non-small-cell lung cancer Trial Evaluating REsponse and Survival against Taxotere) and enrolled 1,446 subjects with pre-treated nsclc. The trial was designed to compare the overall survival of subjects treated with oral Iressa to intravenous docetaxel. The results established non-inferiority between Iressa and docetaxel. In addition, Iressa demonstrated a more favorable tolerability profile and superior quality of life for subjects versus docetaxel. Iressa has been approved for the treatment of nsclc in several international markets.
EntreMed issued positive interim results from a phase II trial of MKC-1 for the treatment of metastatic breast cancer. This single agent trial enrolled 40 subjects with metastatic breast cancer who had failed therapy with anthracyclines and taxanes. The subjects received orally administered MKC-1 (125 mg/m2) twice-daily on a 28 day dosing schedule. Of 35 evaluable subjects there was one complete response, two partial responses and three stable diseases of greater than four months. Based on the results the second stage of this trial has commenced and is enrolling an additional 53 subjects to assess objective response rates.
April 23, 2007
Telik announced positive results from a phase II trial of Telcyta in combination with carboplatin and paclitaxel for the treatment of non-small cell lung cancer. This dose-ranging trial enrolled 129 subjects with Stage IIIB or IV non-small cell lung cancer. Subjects received standard doses of carboplatin and paclitaxel and one of four doses of Telcyta (400, 500, 750 or 1,000 mg/m2) for a course of four to six cycles. Subjects with objective responses or stable disease following completion of combination therapy could elect to receive every three week maintenance cycles of Telcyta as monotherapy until disease progression. The primary endpoints for the intent-to-treat population included safety, objective response and disease stabilization rates, progression-free survival and overall survival. The primary endpoints in the Telcyta maintenance therapy group included safety, progression-free survival and overall survival. The overall objective response rate in the intent-to-treat population was 34% including one complete response. Disease stabilization was seen in 43%, for an overall disease stabilization rate of 77%. Median progression-free survival was 4.9 months, and the overall median survival was 9.6 months. Objective responses or stable disease at the completion of combination therapy was seen in 77% of the enrolled subjects. Half of the subjects received Telcyta maintenance therapy and half did not. Median progression-free survival for those on maintenance therapy was 6.9 months, compared with 4.2 months for those not on maintenance therapy (p< 0.0001, HR 0.36). Overall median survival for the Telcyta-treated subjects was 14.2 months compared with 8.4 months without Telcyta maintenance therapy (p= 0.0003, HR 0.40). Treatment was well tolerated at all doses with no unexpected toxicities. Based on the results Telik plans to move the development of Telcyta forward.
April 4, 2005
Ligand Pharmaceuticals reported negative results of a pair of phase III trials of Targretin (bexarotene), their retinoid X receptor modulator, for the first-line treatment of non-small cell lung cancer (NSCLC) in combination with chemotherapy. Both trials failed to meet the primary endpoint of improved overall survival, with no significant difference observed between subjects receiving Targretin combination therapy and subjects receiving chemotherapy alone. Further, neither trial produced evidence of efficacy in the secondary endpoint, improvements in Kaplan-Meier projected two-year survival. Both trials were dual arm studies which enrolled subjects across sites worldwide. In both studies, patients were randomized to receive either standard chemotherapy (cisplatin/vinorelbine in the first, carboplatin/paclitaxel in the second) alone or in combination with oral doses of Targretin. Based on these results, Ligand announced plans to shift the development focus for Targretin to second- and third-line NSCLC indications.
October 14, 2002
Pharmacyclics reported results from an international, randomized controlled, phase III clinical trial investigating using Xcytrin on non-small cell lung cancer. The researchers concluded that when combined with whole brain radiation therapy (WBRT), Xcytrin significantly slowed the time to neurological progression and decreased deaths due to brain tumor in subjects with brain metastases from lung cancer. There was a significant improvement among the 401 intent-to-treat subject population, with the median time to neurologic progression at 3.8 months with WBRT alone versus 4.3 months with WBRT and Xcytrin. Among lung cancer patients, the median time to neurological progression was 3.7 months with WBRT alone versus 5.5 months with WBRT and Xcytrin. There was a significant reduction in brain tumor deaths among lung cancer subjects with 51% dying after receiving WBRT alone versus 32.2% after receiving WBRT and Xcytrin. Additionally, positive interim results were also reported for Xcytrin in an ongoing phase II clinical trial studying primary brain tumors (glioblastoma multiforme, or GBM).
August 26, 2002
Based on the results of the phase III INTACT trials, AstraZeneca announced that Iressa (ZD1839) does not provide improvement in survival when used in combination with standard platinum-based chemotherapy in subjects with advanced non-small cell lung cancer (NSCLC). Iressa is an Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor that has been approved in Japan as a monotherapy for NSCLC and is under review in the U.S. for the same indication.
June 3, 2002
Phase II trial results indicate that 12% of advanced non-small cell lung cancer (NSCLC) subjects experienced a reduction in tumor size with Iressa (ZD-1839) treatment (250 mg daily dose). In the double-blind "IDEAL 2" trial, 216 subjects were randomized to receive Iressa at either 250 mg/day or 500 mg/day. All subjects had received at least two prior chemotherapy regimens, including platinum-based therapy and docetaxel. The tumor response rate for the 500 mg/day Iressa group was 8.8%, while symptom response rates were 43% with 250 mg/day and 35% with 500 mg/day. Iressa is being developed by AstraZeneca.