A multicenter phase II study of AMG 337 in patients with MET-amplified gastric/gastroesophageal junction/esophageal adenocarcinoma and other MET-amplified solid tumors

Eric Van Cutsem, Boguslawa Karaszewska, Yoon Koo Kang, Hyuncheol Chung, Veena Shankaran, Salvatore Siena, Ning F. Go, Hui Yang, Marco Schupp, David Cunningham

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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 languageEnglish
Pages (from-to)2414-2423
Number of pages10
JournalClinical Cancer Research
Volume25
Issue number8
DOIs
Publication statusPublished - 2019 Apr 15

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Esophagogastric Junction
Stomach
Adenocarcinoma
Neoplasms
Disease-Free Survival
Safety
Survival
Gene Amplification
Appetite
Esophageal Neoplasms
Non-Small Cell Lung Carcinoma
Nausea
Abdominal Pain
Vomiting
Headache
Edema
Pharmacokinetics
AMG-337

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Van Cutsem, Eric ; Karaszewska, Boguslawa ; Kang, Yoon Koo ; Chung, Hyuncheol ; Shankaran, Veena ; Siena, Salvatore ; Go, Ning F. ; Yang, Hui ; Schupp, Marco ; Cunningham, David. / A multicenter phase II study of AMG 337 in patients with MET-amplified gastric/gastroesophageal junction/esophageal adenocarcinoma and other MET-amplified solid tumors. In: Clinical Cancer Research. 2019 ; Vol. 25, No. 8. pp. 2414-2423.
@article{411d9b5e438242398848d0f2e4994977,
title = "A multicenter phase II study of AMG 337 in patients with MET-amplified gastric/gastroesophageal junction/esophageal adenocarcinoma and other MET-amplified solid tumors",
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.",
author = "{Van Cutsem}, Eric and Boguslawa Karaszewska and Kang, {Yoon Koo} and Hyuncheol Chung and Veena Shankaran and Salvatore Siena and Go, {Ning F.} and Hui Yang and Marco Schupp and David Cunningham",
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A multicenter phase II study of AMG 337 in patients with MET-amplified gastric/gastroesophageal junction/esophageal adenocarcinoma and other MET-amplified solid tumors. / Van Cutsem, Eric; Karaszewska, Boguslawa; Kang, Yoon Koo; Chung, Hyuncheol; Shankaran, Veena; Siena, Salvatore; Go, Ning F.; Yang, Hui; Schupp, Marco; Cunningham, David.

In: Clinical Cancer Research, Vol. 25, No. 8, 15.04.2019, p. 2414-2423.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A multicenter phase II study of AMG 337 in patients with MET-amplified gastric/gastroesophageal junction/esophageal adenocarcinoma and other MET-amplified solid tumors

AU - Van Cutsem, Eric

AU - Karaszewska, Boguslawa

AU - Kang, Yoon Koo

AU - Chung, Hyuncheol

AU - Shankaran, Veena

AU - Siena, Salvatore

AU - Go, Ning F.

AU - Yang, Hui

AU - Schupp, Marco

AU - Cunningham, David

PY - 2019/4/15

Y1 - 2019/4/15

N2 - 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.

AB - 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.

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U2 - 10.1158/1078-0432.CCR-18-1337

DO - 10.1158/1078-0432.CCR-18-1337

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SP - 2414

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JO - Clinical Cancer Research

JF - Clinical Cancer Research

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