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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Carcinoma, Non-Small-Cell Lung Cancer

Intervention / Treatment
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* Drug: INC280


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage IIIB or IV NSCLC (any histology) at the time of study entry Histologically or cytologically confirmed diagnosis of NSCLC that is: EGFR wt as per patient standard of care by a validated test AND ALK-negative rearrangement as part of the patient standard of care by a validated test 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

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cMET GCN ≥ 6<br>Pre-treated patients with cMET GCN ≥ 6 treated with INC280 at 400mg BID | Drug: INC280<br>* cMET GCN ≥ 6 cMET GCN ≥ 4 and < 6 cMET mutations<br>* Other names: capmatinib;|
| Experimental: cMET GCN ≥ 4 and < 6<br>Pre-treated patients with cMET GCN ≥ 4 and < 6 treated with INC280 at 400 mgBID | Drug: INC280<br>* cMET GCN ≥ 6 cMET GCN ≥ 4 and < 6 cMET mutations<br>* Other names: capmatinib;|
| Experimental: cMET mutations<br>Pre-treated patients with cMET mutations regardless of cMET GCN treated with INC280 at 400mg BID | Drug: INC280<br>* cMET GCN ≥ 6 cMET GCN ≥ 4 and < 6 cMET mutations<br>* Other names: capmatinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR based on Central Radiology review/assessment (BIRC) | Proportion of patients with a best overall response defined as complete response (CR) or partial response (PR) by Blinded Independent Review Committee (BIRC) assessment per RECIST 1.1 | at least 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) by BIRC - Key Secondary | Calculated as the time from the date of the first documented CR or PR by Blinded Independent Review Committee (BIRC) per RECIST 1.1 to the first documented progression or death due to any cause for patients with PR or CR. | at least 18 weeks | 
| ORR by Investigator | ORR (complete response (CR)+ partial response (PR)) per RECIST 1.1 by investigator assessment | at least 18 weeks | 
| Duration of Response (DOR) by investigator | DOR per RECIST 1.1 by investigator assessment | at least 18 weeks | 
| Time to Response (TTR) by BIRC | TTR per RECIST 1.1 by BIRC assessment | at least 18 weeks | 
| Time to Response (TTR) by investigator | TTR per RECIST 1.1 by investigator assessment | at least 18 weeks | 
| Disease Control Rate (DCR) by BIRC | DCR per RECIST 1.1 by BIRC assessment | at least 18 weeks | 
| Disease Control Rate (DCR) by investigator | DCR per RECIST 1.1 by investigator assessment | at least 18 weeks | 
| Progression-free Survival (PFS) by BIRC | PFS per RECIST 1.1 by BIRC assessment | at least 18 weeks | 
| Progression-free Survival (PFS) by investigator | PFS per RECIST 1.1 by investigator assessment | at least 18 weeks | 
| Overall Survival (OS) | OS, defined as time from first dose of INC280 to death due to any cause | at least 18 weeks | 
| Cmax profile of INC280 | Pharmacokinetics of INC280 | 6 weeks | 
| Cmax profile of INC280 metabolite CMN288 | Pharmacokinetics of INC280 metabolite CMN288 | 6 weeks | 
| Cmin profile of INC280 | Pharmacokinetics of INC280 | 6 weeks | 
| Cmin profile of INC280 metabolite CMN288 | Pharmacokinetics of INC280 metabolite CMN288 | 6 weeks | 
| Plasma concentration-time profiles of INC280 | Pharmacokinetics of INC280 | 6 weeks | 
| Plasma concentration-time profiles of INC280 metabolite CMN288 | Pharmacokinetics of INC280 metabolite CMN288 | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, lung cancer, lung adenocarcinoma, Non small cell lung carcinoma, Non-small cell lung cancer, MET exon 14 deletion, MET exon 14 skipping, MET exon 14 mutation, MET mutation, MET amplification, MET inhibitor, MET dysregulation, MET activation, MET signaling, MET pathway, MET, cMET, Non Small Cell Lung Cancer, INC280, EGFR wild-type (wt), advanced non-small cell lung cancer, advanced/metastatic disease, Non-small cell lung carcinoma (NSCLC), treatment of lung cancer after first metastasis