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dc.contributor.authorVan Cutsem, E
dc.contributor.authorKaraszewska, B
dc.contributor.authorKang, Y-K
dc.contributor.authorChung, HC
dc.contributor.authorShankaran, V
dc.contributor.authorSiena, S
dc.contributor.authorGo, NF
dc.contributor.authorYang, H
dc.contributor.authorSchupp, M
dc.contributor.authorCunningham, D
dc.coverage.spatialUnited States
dc.date.accessioned2022-09-21T14:21:34Z
dc.date.available2022-09-21T14:21:34Z
dc.date.issued2019-04-15
dc.identifier1078-0432.CCR-18-1337
dc.identifier.citationClinical Cancer Research, 2019, 25 (8), pp. 2414 - 2423en_US
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5499
dc.identifier.eissn1557-3265
dc.identifier.eissn1557-3265
dc.identifier.eissn1557-3265
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.CCR-18-1337
dc.identifier.doi10.1158/1078-0432.CCR-18-1337
dc.identifier.doi10.1158/1078-0432.CCR-18-1337
dc.identifier.doi10.1158/1078-0432.CCR-18-1337
dc.description.abstractPURPOSE: 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.formatPrint-Electronic
dc.format.extent2414 - 2423
dc.languageeng
dc.language.isoengen_US
dc.publisherAMER ASSOC CANCER RESEARCHen_US
dc.relation.ispartofClinical Cancer Research
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserveden_US
dc.subjectAdenocarcinoma
dc.subjectAdult
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectCarcinoma, Non-Small-Cell Lung
dc.subjectDisease-Free Survival
dc.subjectEsophagogastric Junction
dc.subjectFluorouracil
dc.subjectHumans
dc.subjectLung Neoplasms
dc.subjectPyridones
dc.subjectStomach Neoplasms
dc.subjectTriazoles
dc.titleA 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.typeJournal Article
dcterms.dateAccepted2018-10-22
dc.date.updated2022-09-21T14:20:44Z
rioxxterms.versionAMen_US
rioxxterms.versionofrecord10.1158/1078-0432.CCR-18-1337en_US
rioxxterms.licenseref.startdate2019-04-15
rioxxterms.typeJournal Article/Reviewen_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/30366938
pubs.issue8
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-statusPublished
pubs.publisher-urlhttp://dx.doi.org/10.1158/1078-0432.ccr-18-1337
pubs.volume25
icr.researchteamMedicine (RMH)en_US
dc.contributor.icrauthorCunningham, David
icr.provenanceDeposited 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


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