First-in-human study of AMG 337, a highly selective oral inhibitor of MET, in adult patients (pts) with advanced solid tumors.

Abstract

2508 Background: Dysregulation of the MET pathway can promote tumor growth and metastasis, making MET an attractive target for cancer therapy. AMG 337 is an investigational, oral inhibitor of MET kinase activity. This study evaluated the safety, tolerability, pharmacokinetics, and efficacy of AMG 337. Methods: Key eligibility: age ≥ 18 years, advanced solid tumors, measurable disease, ECOG ≤ 2, adequate organ function. AMG 337 was administered orally QD or BID on D1 and D3–28. After 1 week without AMG 337 in the absence of dose-limiting toxicity (DLT) or progression, pts resumed AMG 337 until progression. The starting dose of AMG 337 was 25 mg with planned dose escalation of 50-500 mg QD and 100-200 mg BID (3-9 pts/cohort) until the maximum tolerated dose (MTD, highest dose at which < 33% of pts/cohort had a DLT) was reached or the highest dose was tested. Pts with MET overexpression/amplification/mutation could enroll to the highest dose deemed safe at any time. Results: As of OCT 2013, 66 pts (QD escala...