The purpose of this study is to determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of INC280 in combination with erlotinib in the Phase Ib of this study, and to assess the anti-tumor activity and safety of INC280 alone, and in combination with erlotinib, versus platinum with pemetrexed in the Phase II of this study, in adult patients with EGFR mutated, cMET amplified, advanced/metastatic non-small cell lung cancer with acquired resistance to prior EGFR TKI.
Name: INC280 single agent
Type: DrugINC280 single agent
Name: INC280 in combination with erlotinib
Type: DrugINC280 in combination with erlotinib
Name: Platinum/pemetrexed
Type: DrugPlatinum in combination with pemetrexed
Description: Correlation between IHC determined expression level and PFS
Measure: Phase Ib: Progression Free Survival (PFS) Time: Every 6 weeks, up to 2 yearsDescription: OS, defined as time from the first dose of study treatment to death due to any cause
Measure: Phase Ib: Overall Survival (OS) Time: Every 3 weeks, up to 5 yearsDescription: Safety and tolerability of INC280 in combination with erlotinib assessed by change in vital signs, laboratory results and electrocardiogram (ECG).
Measure: Phase Ib: Number of patients with adverse events (AEs) as a measure of safety and tolerability Time: Every 3 weeks, up to 2 yearsDescription: Composite pharmacokinetics of INC280 in the presence of erlotinib.
Measure: Phase Ib: Plasma concentration-time profiles of INC280 and pharmacokinetic parameters Time: 6 weeksDescription: Composite pharmacokinetics of erlotinib in the presence of INC280.
Measure: Phase Ib: Plasma concentration-time profiles of erlotinib in the presence of INC280 Time: 6 weeksDescription: DCR, proportion of patients with best overall response of CR, PR or SD
Measure: Phase Ib: Disease Control Rate (DCR) Time: Every 6 weeks, up to 2 yearsDescription: DOR, defined as time from the first documented CR or PR to first documented progression or death due to any cause
Measure: Phase Ib: Duration of Response (DOR) Time: Every 6 weeks, up to 2 yearsDescription: PFS, defined as time from the first dose of study treatment to disease progression or death due to any cause
Measure: Phase Ib: Progression-free Survival (PFS) Time: Every 6 weeks, up to 2 yearsDescription: Safety and tolerability of INC280 in combination with erlotinib assessed by change in vital signs, laboratory results and electrocardiogram (ECG).
Measure: Phase Ib: Number of patients with serious adverse events as a measure of safety and tolerability Time: Every 3 weeks, up to 2 yearsAllocation: Randomized
Parallel Assignment
There is one SNP
Safety and tolerability of INC280 in combination with erlotinib assessed by change in vital signs, laboratory results and electrocardiogram (ECG).. Inclusion Criteria: - Locally advanced or metastatic NSCLC - EGFR mutation (L858R and /or ex19del) - cMET amplification by FISH (GCN ≥ 6), - Acquired resistance to EGFR TKI (1st or 2nd génération) - ECOG performance status (PS) ≤ 1. Exclusion Criteria: - Prior treatment with 3rd generation TKI - PhaseII : Prior treatment with any of the following agents: - Crizotinib, or any other cMET inhibitor or HGF-targeting inhibitor. --- L858R ---
- Platinum-based chemotherapy as first line treatment Inclusion Criteria: - Locally advanced or metastatic NSCLC - EGFR mutation (L858R and /or ex19del) - cMET amplification by FISH (GCN ≥ 6), - Acquired resistance to EGFR TKI (1st or 2nd génération) - ECOG performance status (PS) ≤ 1. Exclusion Criteria: - Prior treatment with 3rd generation TKI - PhaseII : Prior treatment with any of the following agents: - Crizotinib, or any other cMET inhibitor or HGF-targeting inhibitor. --- L858R ---