>>ORLANDO, Fla., May 15 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated (Nasdaq: KOSN - News) today presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Orlando, Fla. favorable interim data from two Phase Ib clinical trials evaluating KOS-862 (Epothilone D) in combination with carboplatin (Paraplatin®) and gemcitabine (Gemzar®) in patients with advanced solid tumors. Both trials were open-label, dose-escalation, two-center studies designed to determine the maximum tolerated dose, toxicity profile, pharmacokinetics, and recommended Phase II dose of the combination therapies.
In the trial investigating KOS-862 and carboplatin ("Phase I Trial of KOS-862 in Combination with Carboplatin in Patients with Solid Tumors, abstract #2049), side effects included fatigue, nausea, diarrhea, vomiting, and Grade 1-2 neurosensory effects and neutropenia. One episode of dose-limiting toxicity (hypokalemia) was observed at the highest dose level of KOS-862 (75 mg/m(2)) followed by carboplatin (AUC=6 mg/ml*min), administered weekly for two of three weeks. Patient accrual continues in this trial to define the recommended dose. Of the 12 patients treated with the KOS- 862/carboplatin combination therapy, one patient with ovarian cancer experienced a complete response, and one patient with hepatocellular carcinoma demonstrated a 41 percent decrease in aFP (alpha feto-protein) and stable disease for 21 weeks, providing preliminary evidence of anti-tumor activity. Pharmacokinetic data revealed no apparent drug-drug interactions between the two agents.
In the trial investigating KOS-862 and gemcitabine ("Phase I and Pharmacokinetic Study of Weekly KOS-862 Combined with Gemcitabine in Patients with Advanced Solid Tumors," abstract # 2041), side effects included mild-to- moderate fatigue, nausea, diarrhea, vomiting, and Grade 1-2 neurosensory effects. At the highest dose administered weekly for three of four weeks, dose-limiting toxicities were neutropenia, dehydration and diarrhea. Consequently, a three-week cycle (two weeks on drug, one week off) was selected. No dose-limiting toxicity has been observed to date, and an expansion of the trial is proceeding with the administration of gemcitabine (1000 mg/m(2)) followed by KOS-862 (100 mg/m(2)) for two of three weeks. Of the 14 patients treated with the KOS-862/gemcitabine combination therapy, one patient was observed to have a partial response, and two patients had disease stabilization for more than three months, suggesting evidence of anti-cancer activity. Pharmacokinetic data revealed no apparent drug-drug interactions between the two agents.
"These results confirm the findings of preclinical combination studies suggesting the potential for clinical benefit, low potential for drug-drug interactions, and showing non-overlapping toxicities," said Robert G. Johnson, Jr., M.D., Ph.D., Kosan Executive Vice President, Development, and Chief Medical Officer. "We look forward to completing these Phase Ib combination trials as the basis for evaluating the next steps in our clinical development program for these two combination therapies."
Additional KOS-862 ASCO Data
Preliminary data from a Phase II clinical trial of KOS-862 (Epothilone D) used as a single agent in patients with non-small cell lung cancer (NSCLC) will also be presented at the meeting on Tuesday, May 17, from 8:00 a.m. to 12 Noon. The poster presentation, entitled "A Phase II Study of KOS-862 (Epothilone D) as Second-Line Therapy in Non-Small Cell Lung Cancer" (abstract #7127), will include data resulting from an updated analysis of preliminary data from the Phase II clinical trial.
About KOS-862
KOS-862 is a polyketide that inhibits cancer cell growth in vitro by a mechanism similar to paclitaxel, and preclinical models have shown the compound to be effective against paclitaxel-resistant tumors. KOS-862 continues to be evaluated in Phase II monotherapy trials in breast and prostate cancer, as well as Phase Ib combination trials with Gemzar®, Paraplatin®, and Herceptin®.
Under a global development and commercialization agreement between Kosan and Roche, Roche has the worldwide exclusive right to market and sell KOS-862 and epothilone analogs owned by or licensed to Kosan for the treatment of cancer; Kosan will co-develop and has the right to co-promote Kosan/Roche epothilone products in the U.S. for the treatment of cancer.<<
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