dc.contributor.author | Van Cutsem, E | |
dc.contributor.author | Karaszewska, B | |
dc.contributor.author | Kang, Y-K | |
dc.contributor.author | Chung, HC | |
dc.contributor.author | Shankaran, V | |
dc.contributor.author | Siena, S | |
dc.contributor.author | Go, NF | |
dc.contributor.author | Yang, H | |
dc.contributor.author | Schupp, M | |
dc.contributor.author | Cunningham, D | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2022-09-21T14:21:34Z | |
dc.date.available | 2022-09-21T14:21:34Z | |
dc.date.issued | 2019-04-15 | |
dc.identifier | 1078-0432.CCR-18-1337 | |
dc.identifier.citation | Clinical Cancer Research, 2019, 25 (8), pp. 2414 - 2423 | en_US |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5499 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.CCR-18-1337 | |
dc.description.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.See related commentary by Ma, p. 2375. | |
dc.format | Print-Electronic | |
dc.format.extent | 2414 - 2423 | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | AMER ASSOC CANCER RESEARCH | en_US |
dc.relation.ispartof | Clinical Cancer Research | |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | en_US |
dc.subject | Adenocarcinoma | |
dc.subject | Adult | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Carcinoma, Non-Small-Cell Lung | |
dc.subject | Disease-Free Survival | |
dc.subject | Esophagogastric Junction | |
dc.subject | Fluorouracil | |
dc.subject | Humans | |
dc.subject | Lung Neoplasms | |
dc.subject | Pyridones | |
dc.subject | Stomach Neoplasms | |
dc.subject | Triazoles | |
dc.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. | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-10-22 | |
dc.date.updated | 2022-09-21T14:20:44Z | |
rioxxterms.version | AM | en_US |
rioxxterms.versionofrecord | 10.1158/1078-0432.CCR-18-1337 | en_US |
rioxxterms.licenseref.startdate | 2019-04-15 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/30366938 | |
pubs.issue | 8 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham) | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.) | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1158/1078-0432.ccr-18-1337 | |
pubs.volume | 25 | |
icr.researchteam | Medicine (RMH) | en_US |
dc.contributor.icrauthor | Cunningham, David | |
icr.provenance | Deposited by Mr Arek Surman on 2022-09-21. Deposit type is initial. No. of files: 1. Files: A Multicenter Phase 2 Study of AMG 337 in Patients With MET-Amplified..pdf | |