Clinical Trials /

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

NCT04139317

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CINC280I12201
  • NCT ID: NCT04139317

Conditions

  • Non-small Cell Lung Cancer (NSCLC)

Interventions

DrugSynonymsArms
CapmatinibINC280Combination arm
PembrolizumabKeytruda®, MK-3475Combination arm

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Combination armExperimentalCapmatinib 400 mg twice a day Pembrolizumab 200mg every 3 weeks
  • Capmatinib
  • Pembrolizumab
monotherapyActive ComparatorPembrolizumab 200mg every 3 weeks
  • Pembrolizumab

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS) based on local investigator assessment as per RECIST 1.1
Time Frame:24 months
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Objective response rate (ORR) based on local investigator assessment as per RECIST 1.1
Time Frame:24 months
Safety Issue:
Description: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
Measure:Disease control rate (DCR) based on local investigator assessment as per RECIST 1.1
Time Frame:24 months
Safety Issue:
Description: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
Measure:Time-to-response (TTR) based on local investigator assessment as per RECIST 1.1
Time Frame:24 months
Safety Issue:
Description: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
Measure:Duration of response (DOR) based on local investigator assessment as per RECIST 1.1
Time Frame:24 months
Safety Issue:
Description: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
Measure:Overall survival (OS)
Time Frame:38 months
Safety Issue:
Description:Overall survival is defined as the time from date of randomization to date of death due to any cause
Measure:Antidrug antibodies (ADA) of pembrolizumab
Time Frame:24 months
Safety Issue:
Description:Concentration/presence of ADA to be measured
Measure:AUC of Capmatinib derived from plasma capmatinib concentration
Time Frame:24 months
Safety Issue:
Description:
Measure:Ctrough of Pembrolizumab derived from serum pembrolizumab concentration
Time Frame:24 months
Safety Issue:
Description:
Measure:Cmax of Capmatinib derived from plasma capmatinib concentration
Time Frame:24 months
Safety Issue:
Description:
Measure:Tmax of Capmatinib derived from plasma capmatinib concentration
Time Frame:24 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • capmatinib, pembrolizumab, NSCLC, PD-L1, EGFR, ALK, MET, squamous, non-squamous

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