Phase II of Neoadjuvant and Adjuvant Capmatinib in NSCLC

Study Overview
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Brief Summary
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The purpose of this study is to determine if neoadjuvant capmatinib can improve outcomes in participants with stages I-IIIA non-small cell lung cancer with MET exon 14 mutations and/or high MET amplification beyond those achieved with surgery, chemotherapy, and radiation.

Detailed Description
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This trial is a phase II, two cohort study of neoadjuvant capmatinib treatment (pre-surgery) which will be given for 8 weeks prior to a surgical resection and then followed by a three year adjuvant capmatinib treatment (post surgery). Following treatment, there will be a two year survival follow-up. The two molecularly defined cohorts will be enrolled in parallel. Approximately 38 evaluable participants will be enrolled in the study. During treatment participants will visit their treating physician to assess overall health status which will include lab-work and other safety assessments. Survival follow-up will be every 6 months which can be conducted via a telephone visit for up to approximately 2 years after end of treatment.

Official Title
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Phase II Trial of Neoadjuvant and Adjuvant Capmatinib in Participants With Stages IB-IIIA, N2 and Selected IIIB (T3N2 or T4N2) NSCLC With MET Exon 14 Skipping Mutation or High MET Amplification (Geometry-N)

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: capmatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed NSCLC stage IB-IIIA, N2 and selected IIIB (T3N2 or T4N2) Participant must have either MET exon 14 mutations and/or high level MET amplification Participants must be eligible for surgery and scheduled for surgical resection within approximately 2 weeks after the last does of neoadjuvant study treatment. Exclusion Criteria: Participants with unresectable or metastatic disease. All participants should have brain imaging (either MRI brain or CT brain with contrast) prior to enrollment to exclude brain metastasis. Prior treatment with any MET inhibitor or HGF-targeting therapy Major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior to starting study treatment, or who have not recovered from side effects of such procedure. Prior systemic anti-cancer therapy (chemotherapy, immunotherapy, biologic therapy, vaccine) or investigational agents for NSCLC within the past 3 years. History of or current interstitial lung disease or pneumonitis Other protocol-defined inclusion/exclusion criteria may apply at the end

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>Participants with NSCLC with MET exon 14 skipping mutations, irrespective of MET gene copy number (GCN) will take 400 mg tablet orally twice per day | Drug: capmatinib<br>* 150 mg and 200 mg tablets for oral administration<br>* Other names: INC280;|
| Experimental: Cohort B<br>Participants with NSCLC with high level MET amplification will take 400 mg tablet orally twice per day | Drug: capmatinib<br>* 150 mg and 200 mg tablets for oral administration<br>* Other names: INC280;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major pathological response (MPR) rate based on local review | MPR rate in each cohort defined as the percentage of participants with ≤ 10% residual viable cancer cells | Baseline up to time of surgery (approximately 8 to 10 weeks after first dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete pathologic response (pCR) rate based on central and local review | Complete pathologic response (pCR) rate is defined as the percentage of participants with no residual viable cancer cells. | Baseline up to time of surgery (approximately. 8- 10 weeks after first dose) | 
| Overall response rate (ORR) based on local investigator assessment | Overall response rate (ORR) is defined as the percentage participants with best overall response (BOR) of complete response (CR) or partial response ( PR) according to RECIST v1.1 | Baseline up to time of surgery (approximately 8 - 10 weeks after first dose) | 
| Number of adverse events and serious adverse events as assessed by CTCAE criteria | The occurrence of adverse events will be reported from first day of treatment through end of treatment plus 30 days. Serious adverse events which are treatment related will be reported through the end of study participation. Adverse events also may be detected or through physical examination findings, laboratory test findings, or other assessments. | Baseline up to approximately 40 months | 
| Disease free survival rate (DFS) from start of adjuvant therapy | Defined as the time from end of surgery (start of adjuvant therapy) until the recurrence of cancer or death due to any cause. | From time of surgery and at 24, 36, and 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MET exon 14 skipping mutation, High MET amplification, Neoadjuvant, Prior to surgery, Adjuvant, After surgery, INC280, MET inhibition, adult, capmatinib