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

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

76 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-22

Study Completion Date

2023-02-07

Brief Summary

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The purpose was 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.

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Detailed Description

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This was a randomized, open-label, multicenter, phase II study evaluating the efficacy and safety of capmatinib plus pembrolizumab in comparison to pembrolizumab alone as first line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) with programmed cell death ligand-1 (PD-L1) expression ≥ 50%, mesenchymal epithelial transition (MET) unselected, epidermal growth factor receptor (EGFR) wild type and anaplastic lymphoma kinase (ALK) negative.

All eligible subjects were randomized to one of the treatment arms in a 2:1 (capmatinib plus pembrolizumab: pembrolizumab alone) ratio. Participants in both treatment arms were to receive up to 35 cycles (approximately 24 months) of study treatment. The study enrollment was halted on 21-Jan-2021 per sponsor's decision. The enrollment halt decision was based on lack of tolerability observed in the capmatinib plus pembrolizumab arm.

Immediately following the enrollment halt, the below procedural changes were performed:

* Capmatinib treatment was discontinued in subjects on the combination arm. All ongoing subjects were allowed to continue receiving pembrolizumab single agent treatment as per investigator's discretion until unacceptable toxicity, or disease progression, or up to 35 cycles of treatment, whichever occurred first.
* Termination of capmatinib pharmacokinetics (PK) sample collection.
* Termination of pembrolizumab PK/immunogenicity (IG) sample collection. After the enrollment halt, the study protocol was amended (amendment 03) and the collection of efficacy data was stopped. As pembrolizumab is a registered and commercialized treatment for the study indication, the efficacy and safety assessments were to be performed as per each institution's standard of care and no longer captured in the electronic Case Report Form (eCRF) (except reporting of adverse events). Additionally, as single-agent pembrolizumab is a well-established standard treatment for the study indication, the requirement for post-treatment disease progression follow-up and survival follow-up were removed.

Conditions

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Non-small Cell Lung Cancer (NSCLC)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Capmatinib 400mg BID + pembrolizumab 200mg Q3W

Capmatinib (INC280) 400 mg orally twice daily (BID) in combination with pembrolizumab 200 mg intravenously every 3 weeks (Q3W)

Group Type EXPERIMENTAL

Capmatinib

Intervention Type DRUG

INC280 tablets were administered orally at 400 mg on a continuous twice daily (BID) dosing schedule, from Day 1 until Day 21 of each 21-day cycle.

Pembrolizumab

Intervention Type BIOLOGICAL

Pembrolizumab was administered by intravenous infusion at 200 mg once every 3 weeks (Q3W).

Pembrolizumab 200mg Q3W

Pembrolizumab 200 mg intravenously every 3 weeks (Q3W)

Group Type ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type BIOLOGICAL

Pembrolizumab was administered by intravenous infusion at 200 mg once every 3 weeks (Q3W).

Interventions

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Capmatinib

INC280 tablets were administered orally at 400 mg on a continuous twice daily (BID) dosing schedule, from Day 1 until Day 21 of each 21-day cycle.

Intervention Type DRUG

Pembrolizumab

Pembrolizumab was administered by intravenous infusion at 200 mg once every 3 weeks (Q3W).

Intervention Type BIOLOGICAL

Other Intervention Names

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INC280 Keytruda® MK-3475

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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No