Study of INC280 in Patients With c-MET Dependent Advanced Solid Tumors

A Phase I Open-label Dose Escalation Study With Expansion to Assess the Safety and Tolerability of INC280 in Patients With c-MET Dependent Advanced Solid Tumors

This study will assess the safety and efficacy of INC280 in patients with solid tumors that are refractory to current treatment or for which there is not a current standard of care and whose tumors have dysregulation of the c-MET pathway.

Inclusion Criteria:

• Must have evidence of c-MET dysregulation from either local data or the results of molecular pre-screening evaluations.
• Confirmed diagnosis of a solid tumor.
• Measureable lesion.
• Refractory to currently available treatment or no therapies available.
• 18 years or older.
• ECOG performance status of 0, 1, or 2.
• Obtained written informed consent.

Additional inclusion criteria for NSCLC patients EGFRwt with high c-MET expression:

• Written documentation of EGFRwt NSCLC.
• Written documentation of c-MET positivity.
• Patients should not have received more than three prior lines of antineoplastic therapy for NSCLC.
• Presence of at least one measurable lesion as determined by modified RECIST version 1.1

Exclusion Criteria:

HCC with liver dysfunction greater than Child-Pugh A. Previous treatment with a c-MET inhibitor or HGF-targeting therapy. Symptomatic CNS metastases that are neurologically unstable or requiring increasing doses of steroids to control their CNS disease.

Any CNS deficits. For patients with GBM, CNS symptoms grade 2 or greater. Subjects with significant or uncontrolled cardiovascular disease (eg, uncontrolled hypertension, peripheral vascular disease, congestive heart failure, cardiac arrhythmia, or acute coronary syndrome) within 6 months of starting study treatment or heart attack within 12 months of starting study treatment.

Receiving anti-epileptic drugs that are known to be strong inducers of CYP3A4. Prior or current anti-angiogenic therapy for patients with GBM. Radiation therapy within ≤ 4 weeks (< 12 for GBM) prior to the first dose of study drug or limited field radiotherapy within ≤ 2 weeks (< 12 weeks GBM) prior to the start of study treatment. Any persistent side effect of prior radiotherapy must be resolved to ≤ Grade 1 prior to the first dose of study drug.

Additional exclusion criteria for NSCLC patients EGFRwt with high c-MET expression:

• Patients who have received more than three prior lines of antineoplastic therapies

• Any unresolved toxicity (CTCAE grade > 1) from previous anti-cancer therapy or radiotherapy, except alopecia

• Patients have received anti-cancer therapies within the following time frames prior to the first dose of study treatment:

  • Conventional cytotoxic chemotherapy: ≤4 weeks (≤6 weeks for nitrosoureas and mitomycin-C)
  • Biologic therapy (e.g., antibodies): ≤4 weeks
  • Non-cytotoxic small molecule therapeutics: ≤5 half-lives or ≤2 weeks (whichever is longer)
  • Other investigational agents: ≤4 weeks
  • Radiation therapy (palliative setting is allowed.): ≤4 weeks
  • Major surgery: ≤2 weeks

Other protocol-defined inclusion/exclusion criteria may apply.