Study of Oral cMET Inhibitor INC280 in Chinese Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer (NSCLC)

Phase II Multicenter 3-cohort Study of Oral cMET Inhibitor INC280 in Chinese Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer (NSCLC) Who Have Received 1 or 2 Prior Lines of Systemic Therapy for Advanced/Metastatic Disease

A phase II study to evaluate antitumor activity of oral cMET inhibitor INC280 in adult Chinese patients with EGFR wild-type, advanced non-small cell lung cancer (NSCLC) who have received one or two prior lines of systemic therapy for advanced/metastatic disease as measured by overall response rate (ORR). The study will also evaluate safety and pharmacokinetics of INC280.

Inclusion Criteria:

• Stage IIIB or IV NSCLC (any histology) at the time of study entry

• Histologically or cytologically confirmed diagnosis of NSCLC that is:

  1. EGFR wt as per patient standard of care by a validated test

  2. AND ALK-negative rearrangement as part of the patient standard of care by a validated test

  3. AND (by central assessment) either:

     • Cohort 1: Pre-treated patients with cMET GCN ≥ 6 or
     • Cohort 2: Pre-treated patients with cMET GCN ≥4 and < 6, or
     • Cohort 3: Pre-treated patients with cMET mutations regardless of cMET GCN, or

• Patients must have failed one or two prior lines of systemic therapy for advanced/metastatic disease

• At least one measurable lesion as defined by RECIST 1.1

• Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (CTCAE v 4.03). Patients with any grade of alopecia are allowed to enter the study.

• Patients must have adequate organ function

• ECOG performance status (PS) of 0 or 1

Details and other protocol-defined inclusion criteria may apply

Exclusion Criteria:

• Prior treatment with crizotinib, or any other cMET or HGF inhibitor

• Patients with characterized EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 mutations

• Patients with characterized ALK-positive rearrangement

• Clinically significant, uncontrolled heart diseases.

• Patients receiving treatment with medications that cannot be discontinued at least 1 week prior to first INC280 treatment and for the duration of the study:

  • Strong and moderate inhibitors of CYP3A4
  • Strong inducers of CYP3A4

• Impairment of GI function or GI disease that may significantly alter the absorption of INC280

• Patients receiving treatment with any enzyme-inducing anticonvulsant

• Previous anti-cancer and investigational agents within 4 weeks or ≤ 5 x half-life of the agent (whichever is longer) before first dose

• Pregnant or nursing women

• Women of child-bearing potential, unless they are using highly effective methods of contraception

• Sexually active males unless they use a condom during intercourse

Other protocol-defined exclusion criteria may apply