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Capmatinib plus nivolumab in pretreated patients with EGFR wild-type advanced non-small cell lung cancer
Enriqueta Felip1, Giulio Metro2, Daniel S W Tan3
1Medical Oncology Service, Vall d'Hebron Institute of Oncology, Vall d'Hebron Barcelona Hospital Campus, Universitat Autonoma de Barcelona, Spain.
Introduction:
Dysregulated MET is an established oncogenic driver in non-small cell lung cancer (NSCLC). MET signaling may also suppress anticancer immune responses. Concomitant MET inhibition with capmatinib (a MET inhibitor) synergistically enhanced the efficacy of immunotherapies in murine cancer models, regardless of tumor dependency to MET signaling. Here, we report results of a multicenter, open-label, phase 2 study of capmatinib plus nivolumab (a PD-1 inhibitor) in patients with EGFR wild-type advanced NSCLC, previously treated with platinum-based chemotherapy.
Methods:
Patients were allocated into high-MET or low-MET groups according to MET expression determined by immunohistochemistry, MET gene copy number as assessed by fluorescence in-situ hybridization, and presence of MET exon 14 skipping mutation, then received capmatinib 400 mg, oral, twice daily in combination with nivolumab 3 mg/kg intravenously every 2 weeks. The primary endpoint was investigator-assessed 6-month progression-free survival (PFS) rate per RECIST v1.1.
Results:
The primary endpoint was met in both the high-MET (N = 16) and low-MET (N = 30) groups. In the high-MET and low-MET groups, respectively, the estimated mean 6-month PFS rate (95 % credible interval) by Bayesian analysis was 68.9 % (48.5-85.7) and 50.9 % (35.6-66.4). The Kaplan-Meier median PFS (95 % CI) was 6.2 months (3.5-19.2) and 4.2 months (1.8-7.4). The overall response rate (95 % CI) was 25.0 % (7.3-52.4) and 16.7 % (5.6-34.7). Most frequent treatment-related adverse events (≥30 % any grade, N = 46) were nausea (52.2 %), peripheral edema (34.8 %), and increased blood creatinine (30.4 %).
Conclusions:
Capmatinib plus nivolumab showed clinical activity and manageable safety in pretreated patients with advanced EGFR wild-type NSCLC, independent of MET status.
Trial Registration:
ClinicalTrials.gov NCT02323126.
Insights
This study shows capmatinib plus nivolumab offers clinical activity in advanced non-small cell lung cancer (NSCLC) patients. The combination therapy demonstrated manageable safety, regardless of MET status, in previously treated individuals.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Targeted Therapy
Background:
- Dysregulated MET is a key driver in non-small cell lung cancer (NSCLC).
- MET signaling can suppress anti-cancer immune responses.
- Preclinical data suggest MET inhibition enhances immunotherapy efficacy.
Purpose of the Study:
- To evaluate the efficacy and safety of capmatinib plus nivolumab in advanced EGFR wild-type NSCLC.
- To assess the impact of MET expression levels on treatment outcomes.
Main Methods:
- A multicenter, open-label, phase 2 study.
- Patients with previously treated, advanced EGFR wild-type NSCLC were enrolled.
- Patients were stratified into high-MET and low-MET groups based on MET expression and genetic alterations.
- Treatment involved capmatinib (400 mg twice daily) plus nivolumab (3 mg/kg every 2 weeks).
- Primary endpoint was 6-month progression-free survival (PFS) rate.
Main Results:
- The primary endpoint was met in both high-MET and low-MET groups.
- Estimated 6-month PFS rates were 68.9% (high-MET) and 50.9% (low-MET).
- Median PFS was 6.2 months (high-MET) and 4.2 months (low-MET).
- Overall response rates were 25.0% (high-MET) and 16.7% (low-MET).
- Common adverse events included nausea, peripheral edema, and increased creatinine.
Conclusions:
- Capmatinib plus nivolumab demonstrated clinical activity in pretreated advanced EGFR wild-type NSCLC.
- The combination therapy showed manageable safety.
- Treatment efficacy was observed independent of MET status.
