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He AR , Cohen RB , Denlinger CS , Sama A , Birnbaum A , Hwang J , Sato T , Lewis N , Mynderse M , Niland M , Giles J , Wallin J , Moser B , Zhang W , Walgren R , Plimack ER
First-in-Human Phase I Study of Merestinib, an Oral Multikinase Inhibitor, in Patients with Advanced Cancer
Oncologist. 2019 Sep;24(9) :e930-e942
PMID: 30833489    PMCID: PMC6738318    URL: https://www.ncbi.nlm.nih.gov/pubmed/30833489
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Abstract
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.
Notes
1549-490x He, Aiwu Ruth Cohen, Roger B Denlinger, Crystal S Sama, Ashwin Birnbaum, Ariel Hwang, Jimmy Sato, Takami Lewis, Nancy Mynderse, Michelle Niland, Michele Giles, Jennifer Wallin, Johan Moser, Brian Zhang, Wei Walgren, Richard Plimack, Elizabeth R Journal Article United States Oncologist. 2019 Sep;24(9):e930-e942. doi: 10.1634/theoncologist.2018-0411. Epub 2019 Mar 4.