Myers, Andrea, ISHIHARA, KAE, NATSUME, KAZUTO, KAKIZUME, TOMOYUKI, ESAKI, TAITO, HIRAI, FUMIHIKO, MAKIYAMA, AKITAKA, SETO, TAKASHI, BANDO, HIDEAKI, YOICHI, NAITO, YOH, KIYOTAKA and DOI, TOSHIHIKO (2019) Phase I dose-escalation study of capmatinib (INC280) in Japanese patients with advanced solid tumors. Cancer Science, 110 (4). pp. 1340-1351. ISSN 1347-90321349-7006

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). Primary objective was to determine maximum tolerated dose (MTD) and/or highest studied dose being safe. Secondary objectives included safety, pharmacokinetics, and preliminary anti-tumor activity. Dose-escalation was guided by a Bayesian logistic regression model dependent on dose-limiting toxicities (DLTs) in cycle 1. Forty-four adult Japanese patients with confirmed advanced solid tumors were enrolled; 29 patients received capmatinib capsules (doses ranging from 100 mg once daily [qd] to 600 mg twice daily [bid]), and 15 patients 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 in tablets was 400 mg bid, while it was not yet determined with 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 Tmax ranged from 1.0 to 4.0 hours, while absorption was more rapid after dosing using tablet, with median Tmax of 1.0 hour on both day 1 and day 15. Eight patients had a best overall response of stable disease. These data support further clinical development of capmatinib. (Trial registration no. NCT01546428)

Item Type:	Article
Date Deposited:	18 Apr 2019 00:45
Last Modified:	18 Apr 2019 00:45
URI:	https://oak.novartis.com/id/eprint/38277