June 4, 2012
Genta has released results from a phase II trial of tesetaxel for the second-line treatment of advanced gastric cancer. This multi-center, multi-arm, confirmatory study enrolled 53 subjects who had progressed on at least one prior chemotherapy regimen that included a platinum compound (cisplatin, oxaliplatin, or carboplatin) and a fluoropyrimidine (5-fluorouracil, capecitabine), or TS-1. Subjects were divided into three cohorts: cohorts 1 and 2 received fixed oral doses of tesetaxel starting at 40-45mg and 50-60mg, respectively; cohort 3 received the maximally tolerable starting dose of tesetaxel 27mg/m2, specified in Gentas randomized multinational trial. Doses were repeated every three weeks. The overall response rate in cohorts 1, 2 and 3 were 8%, 15% and 21%, respectively. Median survival in cohorts 1 and 2 was 7.6 and 7.5 months, whereas median survival has not yet been reached in cohort 3. The drug was generally well tolerated. Most common adverse events included neutropenia, anemia and anorexia. Based on these results, Genta has initiated the TESEGAST study, a multinational, randomized, placebo-controlled phase II trial of tesetaxel in advanced gastric cancer.
April 16, 2012
Bayer reported initial results from a phase III trial of regorafenib for the third-line treatment of gastrointestinal stromal tumors. This randomized, double-blind, placebo-controlled, multi-center, cross-over study, GRID, enrolled 199 subjects whose cancer had progressed following initial treatment with at least imatinib and sunitinib as prior treatment regimens. The subjects received either regorafenib 160 mg once daily or placebo. The primary endpoint, progression free survival, was reached with statistical significance. Safety and tolerability of regorafenib were consistent with what was seen in earlier studies.
February 6, 2012
AB Science released results from a phase II trial of masitinib for the treatment of Gleevec-resistant gastrointestinal stromal tumors. The study enrolled 44 subjects with inoperable, locally advanced or metastatic GIST who had disease progression while treated with Gleevec. The subjects received either masitinib at 12 mg/kg/day or Sutent (sunitinib) until progression. After a median follow-up of 14 months, median overall survival was not reached for masitinib versus 15 months for Sutent (p≡0.022). After 18 months, 79% of subjects treated with masitinib were still alive, versus 20% for subjects treated with Sutent. After 2 years, 53% of subjects treated with masitinib were still alive, versus 0% for the subjects treated with Sutent. Masitinib was also significantly better tolerated than Sutent and had a better safety profile.
October 18, 2010
ACT Biotech issued positive results from a phase II trial of telatinib for the first-line treatment of advanced gastric cancer. This open label trial enrolled 48 subjects who received full-dose telatinib, administered continuously in combination with a standard regimen of capecitabine and cisplatin. Data are from 32 evaluable subjects. The overall response rate was 66% and telatinib resulted in a rapid and durable objective tumor response. The treatment was well-tolerated and revealed no new or unexpected toxicities.
January 19, 2009
Novartis reported positive results from a phase II trial of Afinitor for the treatment of gastric cancer. This open label, single arm, multi-center enrolled 54 subjects with advanced gastric cancer, whose disease progressed despite prior treatment, in Japan. The subjects received Afinitor 10 mg daily for an average treatment duration of eight weeks. The primary endpoint was disease control rate (DCR). Secondary endpoints included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), and safety. There was an average DCR (complete response/partial response/stable disease) of 55% at eight weeks. Of the 53 subjects evaluated for the primary endpoint, 29 (55%) had stable disease, 22 subjects (41%) had progressive disease and 2 subjects (4%) had an unknown response. The ORR was zero. The median PFS was 83 days, with 29.6% of subjects estimated to still be progression-free at four months. Median overall survival was not available at this time. Afinitor was well tolerated. Based on the results, Novartis plans to move forward with phase III trials.
Novartis reported positive results from a phase IIIb trial of Sandostatin LAR for the treatment of metastatic neuroendocrine tumors of the midgut. This multicenter, prospective, randomized, placebo-controlled, double-blind, study, called PROMID, enrolled 85 treatment-naive subjects in Germany. The subjects received either Sandostatin LAR or placebo until tumor progression. After six months of treatment, subjects receiving Sandostatin LAR had a 66% reduction in risk of disease progression compared to those taking placebo (p≡0.000072). Sandostatin LAR halted tumor growth in 69% of subjects compared with 39% of those receiving placebo. In addition, in the Sandostatin LAR group no tumor progression was observed for a median of 14.3 months, compared to six months for the placebo group. Treatment was well tolerated. Additional studies are underway evaluating Sandostatin LAR for the treatment of various types of neuroendocrine tumors.
June 18, 2007
Genta reported positive results from a phase II trial of Ganite for the treatment of non-Hodgkin's lymphoma, at the 43rd Annual Meeting of the American Society of Clinical Oncology. This trial, dubbed GaRD, enrolled 22 subjects who had failed prior treatment with rituximab. Subjects received Ganite in combination with rituximab and dexamethasone. Overall, 41% of the subjects achieved a major objective response, including 36% with complete or unconfirmed complete responses and 5% with a partial response. Two major responders had previously failed stem cell transplantation and both sustained remission 14+ and 18+ months after their last relapse. Six subjects achieved stable disease. Of all 22 Ganite treated subjects, 46% were alive at a median follow-up of 17+ months, and 7 were currently without evidence of disease. Based on the results Genta is planning a second phase II trial evaluating Ganite in combination with another standard cancer regimen.
Sanofi Aventis and Taiho reported positive results from a phase III trial of S-1 for the treatment of gastric cancer, at the 43rd Annual Meeting of the American Society of Clinical Oncology. This randomized trial, dubbed SPIRTS, enrolled 305 subjects in Japan. Subjects were randomized to receive either oral S-1 (40 mg/m2) twice daily for 28 days followed by a 14-day rest period, or oral S-1(40 mg/m2) twice daily for 21 days plus IV cisplatin on the eighth day of treatment, followed by the 14-day rest period. The primary endpoint was overall survival (OS). Secondary endpoints included Response Rate, Time to Treatment Failure (TTF) and toxicity. Results revealed overall survival with a two-year follow-up was significantly higher in the S-1/cisplatin combination arm compared to the S-1 alone arm, with a median rate of 13 months versus 11 months, respectively (p=0.036). The overall response rate was also significantly higher in the combination arm, with 54% of subjects in the S-1/cisplatin arm showing response to treatment compared with 31.1% with S-1 alone, p=0.001). In addition, S-1 with cisplatin significantly reduced the risk of death by 22.6% (HR: 0.774; 95% CI [0.608-0.985]) over S-1 alone. Several phase III trials of S-1 are underway in the United States.
Telik reported negative top-line results from a phase III trial of Telcyta for the treatment of non-small cell lung cancer (nsclc), at the 43rd Annual Meeting of the American Society of Clinical Oncology. This randomized, active control study, dubbed ASSIST-2, enrolled 530 subjects with advanced NSCLC whose disease had progressed following first-line platinum-based therapy and a second-line treatment. The trial was designed to compare Telcyta to gefitinib. Neither the primary endpoint, superiority in overall survival, nor the secondary endpoint, superiority in progression-free survival was reached. Median survival for the Telcyta arm was 4.6 months as compared with 6.1 months for the active control arm. Median progression-free survival was 2.2 months for the Telcyta arm as compared with 2.3 months for the gefitinib arm. Telcyta is currently in phase III trials for various other indications.
January 29, 2007
BTG issued positive results from a phase I/II trial of plevitrexed for the treatment of metastatic gastric cancer. The phase I portion of this trial enrolled 30 subjects who received plevitrexed at doses of 65 mg/m2, 130 mg/m2 and 165 mg/m2 on days 1 and 8 of a 3-week cycle in combination with nutritional levels of folic acid and vitamin B12. This part of the trial was designed to evaluate the safety, tolerability and maximum tolerated dose (MTD) for the phase II portion, which enrolled an additional 25 subjects and was designed to evaluate efficacy. Treatment was well tolerated with no reported serious adverse events. The MTD was determined to be 130 mg/m2. Of the 28 subjects evaluable for efficacy at this dose level, five (17.9%) had partial response and 15 (53.6%) had stable disease, for an overall disease control rate of 71.4%. One subject treated with plevitrexed at a lower dose of 65 mg/m2 had a complete response and five subjects who received a higher dose of 165 mg/m2 had stable disease. The median progression free survival rate was 120 days and the median overall survival was 239 days. Based on these results, BTG plans to seek a partner to complete the clinical and commercial development of plevitrexed in the treatment of gastric and other types of cancer.
Taiho reported positive interim results from a phase III trial of S-1 for the treatment of gastric cancer. This trial, dubbed ACTS-GC, enrolled 1,059 subjects with stage II or III gastric cancer, in Japan. Subjects were randomized to receive oral S-1 for 12 months at 80-120 mg/day according to the body surface, (administration was 4 weeks on with 2 weeks off in each course, starting within 45 days of surgery until 1 year after surgery), versus curative surgery alone. The primary endpoint was overall survival. Secondary endpoints included relapse free survival and safety. Treatment was generally well tolerated, with the most common reported adverse events including nausea, vomiting and diarrhea. Overall survival at 3-years was 80.5% for subjects receiving S-1 and 70.1% for subjects undergoing surgery alone, with a hazard ratio (HR) of 0.68 (95%CI, 0.52-0.87, p=0.0024). The 3 year relapse free survival was 72.2% in the S-1 arm and 60.1% for surgery alone (p=0.0001) and the reduction of the relative risk of relapse with S-1 was 38% (p < 0.0001). Finally, the relative risk of death for the subjects in the S-1 arm was reduced by 32% as compared to curative surgery alone (p = 0.0024). This drug is currently undergoing phase III trials in the US.
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.