Purpose:MET gene amplification is associated with poor prognosis in gastric/gastroesophageal junction/esophageal (G/GEJ/E) cancers. We determined antitumor activity, safety, and pharmacokinetics of the small-molecule MET inhibitor AMG 337 in MET-amplified G/GEJ/E adenocarcinoma or other solid tumors.Experimental Design: In this phase II, single-arm study, adults with MET-amplified G/GEJ/E adenocarcinoma (cohort 1) or other MET-amplified solid tumors (cohort 2) received AMG 337 300 mg/day orally in 28-day cycles. The primary endpoint was objective response rate (ORR; cohort 1). Secondary endpoints included ORR (cohort 2), progression-free survival (PFS), overall survival (OS), and safety.Results: Of 2101 patients screened for MET amplification, 132 were MET-amplified and 60 were enrolled: 45 in cohort 1, and 15 in cohort 2. Fifty-six patients (97%) had metastatic disease; 57 had prior lines of therapy (1 prior line, 29%; ≥2 prior lines, 69%). A protocol-permitted review showed efficacy that was lower-than-expected based on preliminary data from a first-in-human study, and enrollment was stopped. Fifty-eight patients received ≥1 AMG 337 dose. ORR in cohort 1 was 18% (8 partial responses). No responses were observed in cohort 2. Of 54 evaluable patients, median (95% CI) PFS and OS were 3.4 (2.2-5.0) and 7.9 (4.8-10.9) months, respectively. The most frequent adverse events (AEs) were headache (60%), nausea (38%), vomiting (38%), and abdominal pain, decreased appetite, and peripheral edema (33% each); 71% had grade ≥3 AEs and 59% had serious AEs.Conclusions: AMG 337 showed antitumor activity in MET-amplified G/GEJ/E adenocarcinoma but not in MET-amplified non-small-cell lung cancer.
A Multicenter Phase II Study of AMG 337 in Patients with MET-Amplified Gastric/Gastroesophageal Junction/Esophageal Adenocarcinoma and Other MET-Amplified Solid Tumors / E. Van Cutsem, B. Karaszewska, Y. Kang, H.C. Chung, V. Shankaran, S. Siena, N.F. Go, H. Yang, M. Schupp, D. Cunningham. - In: CLINICAL CANCER RESEARCH. - ISSN 1078-0432. - 25:8(2019), pp. 2414-2423.
|Titolo:||A Multicenter Phase II Study of AMG 337 in Patients with MET-Amplified Gastric/Gastroesophageal Junction/Esophageal Adenocarcinoma and Other MET-Amplified Solid Tumors|
|Parole Chiave:||C-met; gastric-carcinoma; 1st-line therapy; growth-factor; double-blind; amplification; receptor; gene; overexpression; capecitabine|
|Settore Scientifico Disciplinare:||Settore MED/06 - Oncologia Medica|
|Data di pubblicazione:||2019|
|Data ahead of print / Data di stampa:||26-ott-2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1158/1078-0432.CCR-18-1337|
|Appare nelle tipologie:||01 - Articolo su periodico|