MethylGene 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 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 the 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.
The key objectives for the 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 the 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.
Peter O’Dwyer, a principal investigator for the trial, said: 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.