Phase I Study of Ramucirumab Plus Merestinib in Previously Treated Metastatic Colorectal Cancer: Safety, Preliminary Efficacy, and Pharmacokinetic Findings.

The Oncologist
M SalehS Fu

Abstract

The combination of the antivascular endothelial growth factor receptor 2 monoclonal antibody, ramucirumab, and the type II MET kinase inhibitor, merestinib, is tolerable. Preliminary efficacy data suggest that the combination may provide clinical benefit to patients with metastatic colorectal cancer (mCRC). Further development of this combination would likely necessitate the identification of subsets of patients with mCRC where the clinical benefit is of clinical relevance. This study evaluated safety, preliminary efficacy, and pharmacokinetics of ramucirumab plus merestinib in patients with MCR previously treated with oxaliplatin and/or irinotecan. Open-label phase Ia/b study comprising 3+3 dose-limiting toxicity (DLT) observation and expansion parts. Treatment was ramucirumab 8 mg/kg on days 1 and 15 and merestinib 80 mg once daily (QD; 28-day cycle). Primary objective was safety and tolerability. Secondary objectives were pharmacokinetics and preliminary antitumor activity. Exploratory objective was biomarker associations. Safety findings: DLT (proteinuria) of 7 phase Ia patients (the expansion part started at the initial recommended dose level); 16 patients (70%) with grade ≥3 treatment-emergent adverse events (TEAEs); 10 p...Continue Reading

References

May 3, 2003·Cancer Cell·Selma PennacchiettiPaolo M Comoglio
Mar 14, 2009·Biology of the Cell·Eric SulpiceTatyana Merkulova-Rainon
Nov 22, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Priti S HegdeDaniel S Chen
Apr 4, 2015·World Journal of Gastroenterology : WJG·Yan LiuZi-Hua Luo
May 15, 2015·The New England Journal of Medicine·Robert J MayerUNKNOWN RECOURSE Study Group
May 2, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Elmira Safaie QamsariMehdi Yousefi
Sep 28, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·D ArnoldI Chau
Jan 10, 2018·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Aug 4, 2018·Expert Opinion on Drug Safety·Alba NogueridoJosep Tabernero

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