NCT04139317

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

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%

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 76 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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

• Non-small Cell Lung Cancer (NSCLC)

Interventions

Type	Name	Description
DRUG	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.
BIOLOGICAL	Pembrolizumab	Pembrolizumab was administered by intravenous infusion at 200 mg once every 3 weeks (Q3W).

Timeline

• Start date: 2020-01-22
• Primary completion: 2022-01-14
• Completion: 2023-02-07
• First posted: 2019-10-25
• Last updated: 2024-10-09
• Results posted: 2024-02-08

Locations

36 sites across 16 countries: Australia, Belgium, Canada, Czechia, France, Germany, Greece, Hong Kong, India, Italy, Japan, Malaysia, Netherlands, Spain, Taiwan, Thailand

Regulatory

• FDA-regulated drug study