Phase I dose‐escalation study of capmatinib (INC280) in Japanese patients with advanced solid tumors

Abstract

Capmatinib is a highly specific, potent, and selective MET inhibitor. This was an open‐label, multicenter, dose‐escalation, phase I study conducted in Japanese patients with advanced solid tumors (not selected based on their MET status). The primary objective was to determine the maximum tolerated dose (MTD) and/or highest studied dose being safe. Secondary objectives included safety, pharmacokinetics, and preliminary antitumor activity. Dose escalation was guided by a Bayesian Logistic Regression Model dependent on dose‐limiting toxicities (DLTs) in cycle 1. Of 44 adult Japanese patients with confirmed advanced solid tumors enrolled, 29 received capmatinib capsules (doses ranging from 100 mg once daily [qd] to 600 mg twice daily [bid]) and 15 received tablets (200 mg bid and 400 mg bid). DLTs occurred in 2 patients: grade 2 suicidal ideation (600 mg bid capsule) and grade 3 depression (400 mg bid tablet). MTD was not reached. The highest studied dose determined to be safe as tablets was 400 mg bid, whereas it is not yet determined for capsules. Most common adverse events suspected to be drug related were blood creatinine increased, nausea, decreased appetite, vomiting, and diarrhea. Following repeated daily dosing up to day 15 by qd or bid regimen using capsules, median time to reach maximum plasma drug concentration (T_max) was 1.0‐4.0 hours; absorption was more rapid after dosing using tablets, with median T_max of 1.0 hour on both days 1 and 15. Eight patients had a best overall response of stable disease. These data support further clinical development of capmatinib.

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