In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 3_suppl ( 2015-01-20), p. 1-1
Abstract:
1 Background: Dysregulation of the MET pathway can promote tumor growth and metastasis. AMG 337 is an investigational, oral MET kinase inhibitor that is being evaluated in a first-in-human study. Here we describe the clinical activity, safety, and tolerability of AMG 337 in ptswith MET-amplified GEJ, G, and E cancers. Methods: Key eligibility criteria: age ≥ 18 years, advanced solid tumors, measurable disease, ECOG ≤ 2, adequate organ function. AMG 337 was administered QD or BID. Starting dose was 25 mg, with planned dose escalation of 50–500 mg QD and 100–200 mg BID. Ptswith MET overexpression/amplification/mutation could enroll to the highest dose deemed safe at any time. Results: As of April 2014, 80 pts had received ≥ 1 dose of AMG 337. Median (range) age, 58 (19–79) years; men, 61%; ECOG ≤ 1, 96%. Of the 51 pts with pre- and post-central read data, 10 pts had MET-amplified GI cancers (all of which were GEJ, G, or E cancers). Responses in these pts are shown in the table. One pt had a complete response (duration 100 wks) and 4 pts had partial responses (durations up to 52 wks). The most common treatment-emergent AEs (in 〉 20% of all pts) were headache, nausea, fatigue, vomiting, and constipation. AEs and dose-limiting toxicities were reported previously (Hong et al., ASCO 2014). The AE profile of pts with GI cancers was comparable to that of all ptsenrolled in the study. QD maximum tolerated dose (MTD) is 300 mg; BID MTD has not been reached. Conclusions: Responses to AMG 337 were observed in a subset of pts with MET-amplified GI tumors. A dose-expansion phase will enroll up to 50 ptswith MET-amplified tumors at the MTD. Clinical trial information: NCT01253707. [Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2015.33.3_suppl.1
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2015
detail.hit.zdb_id:
2005181-5
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