A Safety and Efficacy Study of INC280 Alone, and in Combination With Erlotinib, Compared to Chemotherapy, in Advanced/Metastatic Non-small Cell Lung Cancer Patients With EGFR Mutation and cMET Amplification

Study Overview
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Brief Summary
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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.

Detailed Description
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The decision was taken to halt study enrollment with Cohort #3 in Phase Ib. Therefore, activities for the planned Phase II were not initiated. This decision to stop further development of this combination was taken due to the challenge for enrollment in this very rare patient population along with the rapidly evolving disease landscape setting.

Official Title
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A Phase Ib/II, Open-label, Multicenter Trial With Oral cMET Inhibitor INC280 Alone and in Combination With Erlotinib Versus Platinum With Pemetrexed in Adult Patients With EGFR Mutated, cMET-amplified, Locally Advanced/Metastatic Non-small Cell Lung Cancer (NSCLC) With Acquired Resistance to Prior EGFR Tyrosine Kinase Inhibitor (EGFR TKI)

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: INC280 single agent
* Drug: erlotinib


Participation Criteria
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Eligibility Criteria
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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. Concomitant EGFR TKI and platinum based chemotherapy as first line regimen. Platinum-based chemotherapy as first line treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study started as a single assignment study which was to move to a parallel design (3 arms) but the study was stopped after cohort #3 in the phase I part and so never moved into phase 2.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INC280 200mg BID + ERL 150mg QD<br>Subjects who took INC280 200mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD) | Drug: INC280 single agent<br> <br> Drug: erlotinib<br> <br> |
| Experimental: INC280 400mg BID + ERL 150mg QD<br>Subjects who took INC280 400mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD) | Drug: INC280 single agent<br> <br> Drug: erlotinib<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase Ib: Frequency and characteristics of Dose Limiting Toxicity (DLTs) to the INC280 and erlotinib combination | To determine MTD and/or RP2D of INC280 in combination with erlotinib | First 28 days of dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase Ib: Overall response rate (ORR) | ORR, proportion of patients with a best overall response of complete response or partial Response (CR+PR) | Every 3 weeks, up to 5 years | 
| Phase Ib: Disease Control Rate (DCR) | DCR, proportion of patients with best overall response of CR, PR or SD | Every 6 weeks, up to 2 years | 
| Phase Ib: Duration of Response (DOR) | DOR, defined as time from the first documented CR or PR to first documented progression or death due to any cause | Every 6 weeks, up to 2 years | 
| Phase Ib: Progression-free Survival (PFS) | PFS, defined as time from the first dose of study treatment to disease progression or death due to any cause | Every 6 weeks, up to 2 years | 
| Phase Ib: Number of patients with adverse events (AEs) as a measure of safety and tolerability | Safety and tolerability of INC280 in combination with erlotinib assessed by change in vital signs, laboratory results and electrocardiogram (ECG). | Every 3 weeks, up to 2 years | 
| Phase Ib: Plasma concentration-time profiles of INC280 and pharmacokinetic parameters | Composite pharmacokinetics of INC280 in the presence of erlotinib. | 6 weeks | 
| Phase Ib: Plasma concentration-time profiles of erlotinib in the presence of INC280 | Composite pharmacokinetics of erlotinib in the presence of INC280. | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Small Cell Lung Cancer, NSCLC, INC280, erlotinib, advanced/metastatic non-small cell lung cancer, EGFR mutation, cMET amplification, EGFR tyrosine kinase inhibitor (EGFR TKI)