The purpose of this study was 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 200mg BID + ERL 150mg QD INC280 400mg BID + ERL 150mg QD
Name: erlotinib
Type: DrugINC280 200mg BID + ERL 150mg QD INC280 400mg BID + ERL 150mg QD
Description: To determine MTD and/or RP2D of INC280 in combination with erlotinib
Measure: Phase Ib: Frequency and characteristics of Dose Limiting Toxicity (DLTs) to the INC280 and erlotinib combination Time: First 28 days of dosingDescription: ORR, proportion of patients with a best overall response of complete response or partial Response (CR+PR)
Measure: Phase Ib: Overall response rate (ORR) Time: Every 3 weeks, up to 5 yearsDescription: 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 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 weeksAllocation: Non-Randomized
Parallel Assignment
There is one SNP
Composite pharmacokinetics of erlotinib in the presence of INC280.. 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 generation) - 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 generation) - 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 ---