Pharmacokinetics and safety of capmatinib with food in patients with MET-dysregulated advanced solid tumors

ABSTRACTPurpose In the Phase II GEOMETRY mono-1 study, potent and selective mesenchymal-epithelial transition (MET) inhibitor capmatinib exhibited considerable efficacy in MET exon 14 skipping (METex14)–mutated metastatic non–small cell lung cancer at a dose of 400 mg BID. The current recommended is BID tablet formulation, with or without food. This article reports pharmacokinetic (PK) profile, safety, tolerability 300 given food MET-dysregulated advanced solid tumors. Methods multicenter, open-label, I study enrolled adult patients escalation phase, tablets were orally administered food; if tolerated, cohort was to be opened enrollment. expansion higher tolerated doses. Tablets taken within 30 minutes an unrestricted meal type, except on cycle 1 day (C1D1) 7 (C1D7), when they high-fat meal. primary objectives determine doses assess PK variables, secondary objective safety. Findings Overall, 35 (300 BID, n = 8; 27) tumors enrolled; all had received prior antineoplastic therapy, most common site (45.7%). Among PK-evaluable patients, median Tmax for after administration (on C1D1/C1D7) 4.0 5.6 hours across At steady state accumulation low levels (geometric mean ratios, 1.29–1.69), increase exposure (AUCtau Cmax) from There no occurrences dose-limiting toxicity. All experienced least adverse event, treatment-related events occurred 28 (80%; 6; 22), frequent which fatigue (37.1%) nausea (34.3%). Implications Capmatinib formulation up well tumors, safety observations consistent existing profile under fasted conditions. These findings support dosing recommendation ClinicalTrials.gov identifier: NCT02925104.