MethylGene Initiates Phase II Program for Multi-Targeted Kinase Inhibitor MGCD265

Strategic Insights -

MethylGene Inc., a clinical-stage biopharmaceutical company, has initiated its Phase II program for its multi-targeted kinase inhibitor, MGCD265, in combination with two approved anticancer agents, Tarceva and docetaxel. This trial aims to evaluate the safety and efficacy of MGCD265 in patients with advanced metastatic malignancies and non-small cell lung cancer (NSCLC).

Key Takeaways:

  • The Phase II trial will evaluate the safety and efficacy of MGCD265 in combination with Tarceva and docetaxel in patients with advanced metastatic malignancies and NSCLC.
  • The trial will consist of two parallel arms, each evaluating multiple ascending doses of MGCD265 in combination with Tarceva or docetaxel.
  • Key objectives for the first stage of the trial will be to evaluate the safety of the combination treatments, measure pharmacodynamic and pharmacokinetic characteristics, and determine the maximum tolerated dose.
  • In the second stage of the trial, patients with advanced NSCLC will be randomized into one of three study arms: MGCD265 in combination with Tarceva or docetaxel, MGCD265 alone, or Tarceva or docetaxel alone.
  • The trial aims to evaluate the antitumor activity of MGCD265 alone and in combination with Tarceva or docetaxel, progression-free survival, and safety.
  • The c-Met pathway appears important in tumorigenesis, and the amplification of c-Met is believed to be a mechanism of resistance to EGFR inhibitors in NSCLC patients.
  • Dr. Peter J. O'Dwyer, Professor of Medicine at the University of Pennsylvania School of Medicine, is a principal investigator for this trial and commented on the significance of the trial: " … the c-Met pathway appears important in tumorigenesis, and 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."

Statistics:

  • 12 patients in Trial 102 have been evaluated for efficacy at dose levels of 24, 48, 96, and 192 mg/m^2, with a cohort at 340 mg/m^2 currently ongoing.
  • Of these patients, five experienced stable disease per RECIST criteria, including one patient with aggressive bladder cancer who received MGCD265 treatment for 12 cycles (approximately one year).
  • 10 patients have been evaluated for efficacy at dose levels of 24, 48, 96, and 150 mg/m^2 in Trial 101, with a cohort of 300 mg/m^2 currently ongoing.
  • Two of these patients experienced stable disease per RECIST criteria.

Sources:

  • MethylGene Inc. (TSX:MYG)
  • Marketwire
  • Comtex SmarTrend Alert
  • American Society of Clinical Oncology's (ASCO) annual meeting
  • University of Pennsylvania School of Medicine
  • University of Pennsylvania Cancer Center (UPCC)
  • Genentech Inc.
  • OSI Pharmaceuticals Inc.
  • Roche Group
  • Chugai Pharmaceutical Co. Ltd.