Abstract
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. Patients and Methods: 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.
| Original language | English |
|---|---|
| Pages (from-to) | 2414-2423 |
| Number of pages | 10 |
| Journal | Clinical Cancer Research |
| Volume | 25 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2019 Apr 15 |
Bibliographical note
Funding Information:E. Van Cutsem is a consultant/advisory board member for Bayer, Bristol-Myers Squibb, Celgene, Lilly, Merck KgA, MSD, Novartis, Servier, and reports receiving commercial research support from Amgen, Bayer, Boehringer, Bristol-Myers Squibb, Celgene, Ipsen, Lilly, MSD, Merck KgA, Novartis, Roche, and Servier. V. Shankaran reports receiving commercial research grants from Astra-Zeneca, Bayer, and Bristol-Myers Squibb. S. Siena is a consultant/advisory board member for Amgen, Bayer, Bristol-Myers Squibb, Incyte, Merck, Novartis, Roche, and Seattle Genetics. Ning F. Go and Hui Yang are employees and stockholders of Amgen Inc. Marco Schupp is an employee of Amgen (Europe) GmbH and is a stockholder of Amgen Inc. D. Cunningham reports receiving commercial research grants from 4SC, Amgen, AstraZeneca, Bayer, Celgene, Clovis, Eli Lilly, Janssen, MedImmune, Merck, Merrimack, and Sanofi. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
The authors wish to acknowledge Meghan Johnson, PhD, Miranda Trade-well, PhD, and James Balwit, MS, CMPP (Complete Healthcare Communications, LLC, an ICON plc Company, North Wales, PA), whose work was funded by Amgen Inc., and Micah Robinson, PhD (Amgen Inc.), for assistance with writing this manuscript as well as Robert D. Loberg, PhD (Amgen Inc.), for his work in developing and deploying the MET FISH assay. D. Cunningham is funded by the National Institute for Health Research Biomedical Research Centres at the Royal Marsden and Institute of Cancer Research. This study was funded by Amgen Inc.
Publisher Copyright:
© 2018 American Association for Cancer Research.
All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
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