Safety Study of Oral MGCD265 Administered Without Interruption to Subjects With Advanced Malignancies

Open-Label Dose-Escalation Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Daily Oral MGCD265 Administered Without Interruption to Subjects With Advanced Malignancies

In this study, MGCD265, a new anticancer drug under investigation, is given daily to patients with advanced malignancies to study its safety profile.

MGCD265 belongs to a new class of drugs with anticancer potential, known as tyrosine kinase inhibitors. MGCD265 was shown to slow down the growth of human cancer cells in mice. Clinical studies are being pursued to evaluate the safety of MGCD265 in cancer patients.

In this study, MGCD265 is orally administered on a daily basis to patients with advanced malignancies.

Inclusion Criteria:

• Advanced metastatic or unresectable malignancy that is refractory to standard therapy and/or existing therapies are not likely to achieve clinical benefit, and/or the patient declines to receive standard treatment such as chemotherapy.

• Evaluable disease;

• Last dose of prior chemotherapy, radiation therapy, or investigational agents occurred at least 4 weeks before the start of therapy;

• Recovery from the adverse effects ≤ grade 1;

• Acceptable ECOG status 0, 1, or 2;

• Life expectancy greater than 3 months following study entry;

• Adequate laboratory values;

• For patients enrolling in the four expansion cohorts:

  • NSCLC patients must meet criteria for MET and/or Axl expression or,
  • HNSCC patients must meet criteria for MET and/or Axl expression or,
  • NSCLC patients must meet criteria for amplification of the MET gene locus, defined MET mutations, or rearrangements involving the AXL or MET gene locus or;
  • Patients with tumor types such as HNSCC, papillary renal carcinoma, gastric adenocarcinoma, and other solid tumors must meet criteria for amplification of the MET gene locus, defined MET mutations, or rearrangements involving the AXL or MET gene locus

Exclusion Criteria:

• Uncontrolled concurrent illness;
• History of cardiovascular illness;
• QTc > 470 msec (including subjects on medication);
• Left ventricular ejection fraction (LVEF) < 50%;
• Immunocompromised subjects;
• History of bone marrow transplant;
• Lung tumor lesions with increased likelihood of bleeding;
• Symptomatic or uncontrolled brain metastases;
• Unable to swallow oral medications or with pre-existing gastrointestinal disorders.