Safety and Efficacy of Capmatinib (INC280) Plus Pembrolizumab vs Pembrolizumab Alone in NSCLC With PD-L1≥ 50%

Study Overview
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Brief Summary
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The purpose is to evaluate the efficacy and safety of the combination of capmatinib with pembrolizumab compared to pembrolizumab alone as first-line treatment for subjects with locally advanced or metastatic NSCLC who have PD-L1 expression ≥ 50% and have no EGFR mutation or ALK rearrangement. Capmatinib has demonstrated immunomodulatory activities when combined with an anti-PD1 antibody in preclinical tumor models irrespective of MET dysregulation. The combination of capmatinib with checkpoint inhibitors has been established to be tolerable and could provide additional clinical benefit to the subjects.

Official Title
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A Randomized, Open Label, Multicenter Phase II Study Evaluating the Efficacy and Safety of Capmatinib (INC280) Plus Pembrolizumab Versus Pembrolizumab Alone as First Line Treatment for Locally Advanced or Metastatic Non-small Cell Lung Cancer With PD-L1≥ 50%

Conditions
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Non-small Cell Lung Cancer (NSCLC)

Intervention / Treatment
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* Drug: Capmatinib
* Biological: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed and documented locally advanced stage III (not candidates for surgical resection or definitive chemo-radiation) or stage IV (metastatic) NSCLC (per AJCC/IASLC v.8) for treatment in the first-line setting Histologically or cytologically confirmed diagnosis of NSCLC that is both EGFR wild type status and ALK- negative rearrangement statu Have an archival tumor sample or newly obtained tumor biopsy with high PD-L1 expression (TPS ≥ 50%) ECOG performance status score ≤ 1 Have at least 1 measurable lesion by RECIST 1.1 Have adequate organ function Exclusion Criteria: Prior treatment with a MET inhibitor or HGF-targeting therapy Prior immunotherapy (e.g. anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) Have untreated symptomatic central nervous system (CNS) metastases Clinically significant, uncontrolled heart diseases Prior palliative radiotherapy for bone lesions ≤ 2 weeks prior to starting study treatment Other protocol-defined inclusion/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: Combination arm<br>Capmatinib 400 mg twice a day Pembrolizumab 200mg every 3 weeks | Drug: Capmatinib<br>* Oral tablet<br>* Other names: INC280;Biological: Pembrolizumab<br>* IV infusion<br>* Other names: MK-3475;|
| Active Comparator: monotherapy<br>Pembrolizumab 200mg every 3 weeks | Biological: Pembrolizumab<br>* IV infusion<br>* Other names: MK-3475;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) based on local investigator assessment as per RECIST 1.1 | Progression free survival is defined as the time from randomization to the date of the first documented radiological progression using RECIST 1.1(Response evaluation criteria in solid tumor) or death due to any cause | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) based on local investigator assessment as per RECIST 1.1 | ORR is defined as the proportion of subjects with confirmed best overall response of complete response (CR) or partial response (PR), as per investigator's assessment by RECIST 1.1 | 18 months | 
| Disease control rate (DCR) based on local investigator assessment as per RECIST 1.1 | Disease control rate is defined as the proportion of patients with complete response (CR) or partial response (PR) or subjects with stable disease (SD) as per investigator assessment according to RECIST 1.1 criteria | 18 months | 
| Time-to-response (TTR) based on local investigator assessment as per RECIST 1.1 | Time to response (TTR) is defined as duration of time between the date of randomization and the date of first documented response of either CR or PR, according to RECIST 1.1 criteria | 18 months | 
| Duration of response (DOR) based on local investigator assessment as per RECIST 1.1 | Duration of response is defined as the time from first documented response of CR or PR to date of first documented progression or death, according to RECIST 1.1 criteria | 18 months | 
| Overall survival (OS) | Overall survival is defined as the time from date of randomization to date of death due to any cause | 18 months | 
| Antidrug antibodies (ADA) of pembrolizumab | Concentration/presence of ADA to be measured | 13 months | 
| AUC of capmatinib derived from plasma capmatinib concentration | AUC of capmatinib is defined as area under the plasma concentration-time curve determined using non-compartmental methods. | 13 months | 
| Ctrough of pembrolizumab derived from serum pembrolizumab concentration | Ctrough of pembrolizumab is defined as the measured serum concentration at the end of a dosing interval at steady state | 13 months | 
| Cmax of capmatinib derived from plasma capmatinib concentration | Cmax of capmatinib is defined as the maximum observed plasma concentration after single dose administration | 13 months | 
| Tmax of capmatinib derived from plasma capmatinib concentration | Tmax of capmatinib is defined as the time to reach maximum plasma concentration after single dose administration | 13 months | 
| Incidence of adverse events | Incidence of adverse events is defined as number of participants with adverse events (AEs), serious adverse events (SAEs) and AEs leading to dose interruption, dose reduction and dose discontinuation. | 19 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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capmatinib, pembrolizumab, NSCLC, PD-L1, EGFR, ALK, MET, squamous, non-squamous