METHYLGENE INITIATES PHASE II PROGRAM FOR MGCD265 IN SOLID TUMORS
AND NON-SMALL CELL LUNG CANCER PATIENTS
MGCD265 Two-Stage Clinical Trial in Combination with Tarceva® or Docetaxel
Montreal, Quebec. September 2, 2009 – MethylGene Inc. (TSX: MYG) announced it has initiated its Phase II program (Trial 103) evaluating MGCD265, the Company’s multi-targeted (c-Met) kinase inhibitor, in combination with approved anticancer agents Tarceva® (erlotinib, developed by Genentech Inc. - a wholly owned member of the Roche Group, OSI Pharmaceuticals Inc., Roche Group and Chugai Pharmaceutical Co. Ltd.) and docetaxel. The trial will initially enroll patients with advanced metastatic malignancies, followed by patients with non-small cell lung cancer (NSCLC) who have had no prior treatment with either Tarceva or docetaxel. Both Tarceva and docetaxel are therapeutics approved as single agents for use in NSCLC.
The first stage of this open-label trial consists of two parallel arms which will evaluate multiple ascending doses of MGCD265 in combination with Tarceva or docetaxel. For both study arms, MGCD265 will be administered orally on a daily basis for 21-days (one cycle). One arm will include docetaxel which will be administered intravenously once every three weeks (Day 1 of each cycle) and in the other arm, Tarceva will be administered orally on a daily basis. Key objectives for this portion of the study will be to evaluate the safety of the combination treatments, to measure the pharmacodynamic and pharmacokinetic characteristics and to determine the maximum tolerated dose to be used in the second stage of the trial.
In the second stage of the trial, patients with advanced NSCLC (stage 3b or 4) who have failed at least one prior regimen of chemotherapy will be randomized into one of the three study arms: MGCD265 in combination with Tarceva or docetaxel (based on results from the first-stage); MGCD265 alone; or Tarceva or docetaxel alone. Objectives for this stage of the trial will be to evaluate the antitumor activity of MGCD265 alone and in combination with Tarceva or docetaxel, progression-free survival and to further assess safety.
“This Phase II trial is particularly interesting since the c-Met pathway appears important in tumorigenesis and, it has also been shown that c-Met and EGFR, the target of Tarceva, functionally cooperate,” commented Dr. Peter J. O’Dwyer, Professor of Medicine at the University of Pennsylvania School of Medicine / Director of the Experimental Therapeutics Program at the University of Pennsylvania Cancer Center (UPCC) and a principal investigator for this trial. “Importantly, the amplification of c-Met is believed to be a mechanism of resistance to EGFR inhibitors in NSCLC patients; therefore, blocking c-Met offers a compelling rationale to overcome resistance to EGFR inhibitors in this patient population. In addition, docetaxel is a commonly used chemotherapeutic for treating non-small cell lung cancer patients and other solid tumors, and preclinically, it has demonstrated synergy in in vivo studies with MGCD265. I look forward to evaluating MGCD265 in this trial with the goal of improving the outcome for our patients.”
Data Previously Reported for MGCD265 Phase I Trials
In May, preliminary MGCD265 Phase I data from two clinical trials (Trials 101 and 102) evaluating the compound in solid tumors were published in the proceedings from the American Society of Clinical Oncology’s (ASCO) annual
