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.
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
| Drug | Synonyms | Arms |
|---|
| Capmatinib | INC280 | Combination arm |
| Pembrolizumab | Keytruda®, MK-3475 | Combination 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
| Name | Type | Description | Interventions |
|---|
| Combination arm | Experimental | Capmatinib 400 mg twice a day Pembrolizumab 200mg every 3 weeks | |
| monotherapy | Active Comparator | Pembrolizumab 200mg every 3 weeks | |
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: | 18 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: | 18 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: | 18 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: | 18 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: | 18 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: | 18 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: | 13 months |
| Safety Issue: | |
| Description: | Concentration/presence of ADA to be measured |
| Measure: | AUC of capmatinib derived from plasma capmatinib concentration |
| Time Frame: | 13 months |
| Safety Issue: | |
| Description: | AUC of capmatinib is defined as area under the plasma concentration-time curve determined using non-compartmental methods. |
| Measure: | Ctrough of pembrolizumab derived from serum pembrolizumab concentration |
| Time Frame: | 13 months |
| Safety Issue: | |
| Description: | Ctrough of pembrolizumab is defined as the measured serum concentration at the end of a dosing interval at steady state |
| Measure: | Cmax of capmatinib derived from plasma capmatinib concentration |
| Time Frame: | 13 months |
| Safety Issue: | |
| Description: | Cmax of capmatinib is defined as the maximum observed plasma concentration after single dose administration |
| Measure: | Tmax of capmatinib derived from plasma capmatinib concentration |
| Time Frame: | 13 months |
| Safety Issue: | |
| Description: | Tmax of capmatinib is defined as the time to reach maximum plasma concentration after single dose administration |
| Measure: | Incidence of adverse events |
| Time Frame: | 19 months |
| Safety Issue: | |
| Description: | 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. |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- capmatinib, pembrolizumab, NSCLC, PD-L1, EGFR, ALK, MET, squamous, non-squamous
Last Updated
August 25, 2021
