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 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
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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 journal › Article
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
M3 - Article
VL - 25
SP - 2414
EP - 2423
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 8
ER -