First-in-Human Phase I Study of Merestinib, an Oral Multikinase Inhibitor, in Patients with Advanced Cancer

The oncologist

article

Aiwu Ruth He¹  Michele Niland²  Jennifer Giles²  Johan Wallin²  Brian Moser²  Wei Zhang²  Richard Walgren²  Elizabeth R. Plimack³  Roger B. Cohen⁴  Crystal S. Denlinger³  Ashwin Sama⁵  Ariel Birnbaum⁶  Jimmy Hwang⁷  Takami Sato⁵  Nancy Lewis⁸  Michelle Mynderse⁹ 

[1] Department of Medicine, Georgetown University Medical Center;Eli Lilly and Company;Department of Hematology/Oncology, Fox Chase Cancer Center, Temple Health;Perelman School of Medicine at the University of Pennsylvania, Abramson Cancer Center;Department of Medical Oncology, Thomas Jefferson University;Division of Hematology/Oncology, Rhode Island Hospital;Levine Cancer Institute, Carolinas HealthCare System;Translational Clinical Oncology;Syneos Health

关键词: Merestinib;    LY2801653;    Colorectal cancer;    Head and neck squamous cell cancer;    Cholangiocarcinoma;   

DOI  :  10.1634/theoncologist.2018-0411

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Background The purpose of this nonrandomized, open-label, phase I study (NCT01285037) was to evaluate the safety and tolerability of merestinib, an oral antiproliferative and antiangiogenic kinase inhibitor, and to determine a recommended phase II dose and schedule for patients with advanced cancer. Materials and Methods This was a multicenter, nonrandomized, open-label, phase I study of oral merestinib consisting of six parts: dose escalation (part A), followed by a four-cohort dose-confirmation study (part B) and subsequently a four-part dose expansion and combination safety testing of merestinib with standard doses of cetuximab (part C), cisplatin (part D), gemcitabine and cisplatin (part E), and ramucirumab (part F) in patients with specific types of advanced cancers. Safety, tolerability, antitumor activity, and pharmacokinetics were evaluated in all cohorts. Results The dose escalation, confirmation, and expansion results support the dosing of merestinib at 120 mg once daily, based on acceptable exposure and safety at this dose. One complete response was observed in a patient with cholangiocarcinoma, and three patients with cholangiocarcinoma achieved a partial response. Overall, 60 (32%) of the 186 patients enrolled in the study had a best response of stable disease. Conclusion This study demonstrates that merestinib has a tolerable safety profile and potential anticancer activity and warrants further clinical investigation. Implications for Practice Merestinib treatment in patients with advanced cancer demonstrated an acceptable safety profile and potential antitumor activity, supporting its future development in specific disease populations as a monotherapy and/or in combination with other therapies.

【 授权许可】

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