- 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
3. AND (by central assessment) either:
- Cohort 1: cMET GCN 6, or
- Cohort 2: cMET GCN 4 and < 6, or
- Cohort 3: cMET GCN < 4
- Patients must have received one or two prior lines of systemic therapy
- 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
- 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
- Proton pump inhibitors (PPI)
- Impairment of GI function or GI disease that may significantly alter the absorption
- Patients receiving treatment with any enzyme-inducing anticonvulsant.
- Previous anti-cancer and investigational agents.
- Pregnant or nursing women
- Women of child-bearing potential, unless they are using highly effective methods of
- Sexually active males unless they use a condom during intercourse
Other protocol-defined exclusion criteria may apply
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
Duration of Response (DOR) - Key Secondary
Overall Response Rate (ORR)
Duration of Response (DOR)
Time to Response (TTR)
Disease Control Rate (DCR)
Progression-free Survival (PFS)
Overall Survival (OS)
Number of patients with incidence of adverse events and serious adverse events, change in vital signs, laboratory results (hematology, blood chemistry, and urinalysis) and ECG.
Cmax, Cmin and plasma concentration-time profiles of INC280