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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%.