Capmatinib

Ferreira M, et al. Lung Cancer, 2024, 196, 107934.

Capmatinib, a selective MET inhibitor, was evaluated in the IFCT-2104 CAPMATU study involving 146 non-small cell lung cancer (NSCLC) patients harboring MET exon 14 skipping mutations. Administered under the French Early Access Program, capmatinib was given to patients ineligible for or refractory to standard therapies. This multicenter, retrospective study assessed time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Capmatinib yielded a median PFS of 4.8 months and ORR of 55.3%. Notably, treatment-naïve patients showed superior PFS (7.7 months), while patients with brain metastases had a median PFS of 3.0 months. Safety analysis confirmed manageable toxicity, with peripheral edema as the most frequent grade 3-4 adverse event. These real-world findings underscore the clinical utility of capmatinib across diverse and heavily pretreated NSCLC patient subgroups.

Felip E, et al. Lung Cancer, 2024, 192, 107820.

In a multicenter, open-label phase 2 clinical study, Capmatinib was evaluated in combination with the PD-1 inhibitor nivolumab for its therapeutic potential in patients with EGFR wild-type advanced non-small cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy. The study aimed to assess the efficacy of this dual regimen based on MET expression and genetic alteration status.
Patients were stratified into high-MET and low-MET cohorts based on three criteria: MET protein expression via immunohistochemistry (IHC), MET gene copy number assessed through fluorescence in-situ hybridization (FISH), and the presence of MET exon 14 skipping mutations. Capmatinib was administered orally at a dosage of 400 mg twice daily, while nivolumab was delivered intravenously at 3 mg/kg biweekly. The primary endpoint was the 6-month progression-free survival (PFS) rate, evaluated per RECIST v1.1 and analyzed using a Bayesian statistical model.
The combination therapy yielded a 6-month PFS rate of 68.9% in the high-MET group and 50.9% in the low-MET group. Median PFS durations were 6.2 and 4.2 months, respectively. Despite MET status, the combination demonstrated consistent antitumor activity, with manageable safety profiles. Common treatment-related adverse events included nausea (52.2%), peripheral edema (34.8%), and elevated serum creatinine levels (30.4%). This study highlights Capmatinib's potential in synergizing with immune checkpoint inhibitors and supports its continued investigation in MET-dysregulated and MET-independent NSCLC.