First-in-human phase I dose escalation study of MK-8033 in patients with advanced solid tumors.

ABSTRACT: Background C-Met, which is frequently activated in multiple cancers, has been implicated in tumor formation, progression, metastasis, angiogenesis, and resistance to multiple therapies. MK-8033 is a small-molecule inhibitor of c-Met that binds preferentially to the activated conformation, and has demonstrated anti-tumor activity in preclinical models. This first-in-human trial was performed to establish the safety and maximum tolerated dose (MTD), as well as preliminary pharmacokinetics (PK) and clinical activity. Methods Forty-seven patients were enrolled in three parts. The primary objective of Parts A and B was safety, whereas Part C evaluated the effect of proton-pump inhibitors on MK-8033 absorption. Dose escalation used an accelerated continual reassessment method, and dose-limiting

SUBMITTER: Keedy VL 

PROVIDER: S-EPMC7507839 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature