Brief Report: Combination Capmatinib and Trametinib in Metastatic MET-Driven NSCLC.

Introduction: MET tyrosine kinase inhibitor (TKI) therapy has improved outcomes in patients with NSCLC harboring Methods: A multicenter phase I study evaluated capmatinib in combination with trametinib in patients with advanced-stage NSCLC harboring activating Results: Three patients (N = 3) were enrolled in the study and completed a median of three cycles of therapy. Dose-limiting toxicities, including rash, edema, and nausea, necessitated dose reductions in the first two patients and the initiation of therapy in the third patient at a lower dose level. Ultimately, all patients discontinued therapy because of treatment-related adverse events (TRAEs). The study was terminated early because of poor accrual and TRAEs. No radiographic objective responses were observed. Conclusions: In this phase I trial, capmatinib plus trametinib was associated with marked TRAEs, and treatment was discontinued in all participants. On the basis of these findings, further investigation of this combination of MET and MEK inhibitors at the tested dose levels is not recommended. Future studies, if pursued, should consider modified dosing strategies, alternative MET and MEK inhibitor combinations, and ClinicalTrialsgov Identifier: NCT05435846.