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

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.