{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T14:44:21Z","timestamp":1754145861109,"version":"3.41.2"},"reference-count":12,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004755","name":"EMD Serono","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004755","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009945","name":"Merck KGaA","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009945","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Darmstadt"},{"name":"Germany"},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of North Carolina Lineberger Comprehensive Cancer Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Trastuzumab and multiagent chemotherapy have been the standard of care for the 20-30% of metastatic gastric and esophageal adenocarcinomas that overexpress HER2. Preclinical data show that trastuzumab requires a functional adaptive immune system for efficacy, suggesting synergy of trastuzumab combined with immune checkpoint inhibitors, further supported by current clinical studies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>HCRN GI17-319 was a multicenter, single-arm, phase II clinical trial with a prespecified 6-subject safety run-in of the anti-PD-L1 antibody avelumab, combined with trastuzumab and mFOLFOX6, in previously untreated, metastatic, HER2-amplified gastric and esophageal adenocarcinomas. The primary endpoint was the best overall response within 24 weeks. Subjects received 9 cycles of induction avelumab, trastuzumab, and mFOLFOX6, followed by maintenance avelumab\u2005+\u2005trastuzumab. The study was initially designed as a Simon\u2019s 2-stage trial, but enrollment was stopped after the 18-subject first stage for reasons unrelated to safety or efficacy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 18 subjects, including the 6-subject safety run-in, were enrolled 4\/2019-8\/2020. The 24-week response rate was 11\/18 (61%; 95% CI: 39%-84%), and the confirmed overall response rate is 9\/18 (50%). With a median follow-up of 14.6 months, the median PFS was 8.0 months (95% CI: 5.3-NA) and median OS was 13.1 months (95% CI: 11.5-NA). The regimen was well tolerated, without any new safety signals.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The combination of avelumab, trastuzumab, and FOLFOX chemotherapy demonstrated some activity, with a reasonable response rate and median PFS. These outcomes provide some support to other clinical trials of similar agents and support the future evaluation of adding avelumab in this setting. NCT03783936.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyaf195","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T21:49:26Z","timestamp":1750974566000},"source":"Crossref","is-referenced-by-count":0,"title":["Phase II study of avelumab and trastuzumab with FOLFOX chemotherapy in previously untreated HER2-amplified metastatic gastroesophageal adenocarcinoma"],"prefix":"10.1093","volume":"30","author":[{"given":"Michael S","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Innovative Medicine Research & Development, Johnson and Johnson Innovative Medicine Research & Development, LLC , Spring House, PA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Medicine, City of Hope Comprehensive Cancer Center , Duarte, CA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary F","family":"Mulcahy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Northwestern University , Chicago, IL ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pashtoon M","family":"Kasi","sequence":"additional","affiliation":[{"name":"Department of Medicine, City of Hope Comprehensive Cancer Center , Duarte, CA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela T","family":"Alistar","sequence":"additional","affiliation":[{"name":"Department of Medicine, Morristown Medical Center , Morristown, NJ ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2153-3896","authenticated-orcid":false,"given":"Sarbajit","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Roswell Park Cancer Center , Buffalo, NY ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehmet","family":"Akce","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham , Birmingham, AL ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominic T","family":"Moore","sequence":"additional","affiliation":[{"name":"University of North Carolina Lineberger Comprehensive Cancer Center , Chapel Hill, NC ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2868-1576","authenticated-orcid":false,"given":"Autumn J","family":"McRee","sequence":"additional","affiliation":[{"name":"Department of Innovative Medicine Research & Development, Johnson and Johnson Innovative Medicine Research & Development, LLC , Spring House, PA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3167-406X","authenticated-orcid":false,"given":"Ashwin","family":"Somasundaram","sequence":"additional","affiliation":[{"name":"University of North Carolina Chapel Hill, Department of Medicine at Chapel Hill , NC ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"2025071710064095000_CIT0001","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/S1470-2045(23)00515-6","article-title":"A multi-institutional phase Ib\/II trial of first-line triplet regimen (Pembrolizumab, Trastuzumab, Chemotherapy) for HER2-positive advanced gastric and gastroesophageal junction cancer (PANTHERA Trial): Molecular profiling and clinical update","volume":"39","author":"Rha","year":"2021","journal-title":"J Clin Oncol"},{"key":"2025071710064095000_CIT0002","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/S1470-2045(20)30169-8","article-title":"First-line pembrolizumab and trastuzumab in HER2-positive oesophageal, gastric, or gastro-oesophageal junction cancer: an open-label, single-arm, phase 2 trial","volume":"21","author":"Janjigian","year":"2020","journal-title":"Lancet Oncol"},{"key":"2025071710064095000_CIT0003","doi-asserted-by":"publisher","first-page":"4013","DOI":"10.1200\/jco.2021.39.15_suppl.4013","article-title":"Pembrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction (G\/GEJ) cancer: Initial findings of the global phase 3 KEYNOTE-811 study","volume":"39","author":"Janjigian","year":"2021","journal-title":"J Clin Oncol"},{"key":"2025071710064095000_CIT0004","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1016\/s0140-6736(23)02033-0","article-title":"Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial","volume":"402","author":"Janjigian","year":"2023","journal-title":"Lancet"},{"key":"2025071710064095000_CIT0005","doi-asserted-by":"publisher","first-page":"2196","DOI":"10.1093\/annonc\/mdw423","article-title":"Ramucirumab combined with FOLFOX as front-line therapy for advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: a randomized, double-blind, multicenter Phase II trial","volume":"27","author":"Yoon","year":"2016","journal-title":"Ann Oncol"},{"key":"2025071710064095000_CIT0006","doi-asserted-by":"publisher","first-page":"1430","DOI":"10.1016\/S1470-2045(22)00603-9","article-title":"Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): a randomised, double-blind, placebo-controlled, phase 2 study","volume":"23","author":"Wainberg","year":"2022","journal-title":"Lancet Oncol"},{"key":"2025071710064095000_CIT0007","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1016\/S0140-6736(10)61121-X","article-title":"Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial","volume":"376","author":"Bang","year":"2010","journal-title":"Lancet"},{"key":"2025071710064095000_CIT0008","doi-asserted-by":"publisher","first-page":"2558","DOI":"10.1200\/JCO.2016.71.6852","article-title":"HELOISE: Phase IIIb randomized multicenter study comparing Standard-of-Care and Higher-Dose trastuzumab regimens combined with chemotherapy as First-Line therapy in patients with human epidermal growth factor receptor 2-Positive metastatic gastric or gastroesophageal junction adenocarcinoma","volume":"35","author":"Shah","year":"2017","journal-title":"J Clin Oncol"},{"key":"2025071710064095000_CIT0009","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1001\/jamaoncol.2019.5367","article-title":"Use of immunotherapy with programmed cell death 1 vs programmed cell death ligand 1 inhibitors in patients with cancer: a systematic review and Meta-analysis","volume":"6","author":"Duan","year":"2020","journal-title":"JAMA Oncol"},{"key":"2025071710064095000_CIT0010","doi-asserted-by":"publisher","first-page":"3158","DOI":"10.1158\/1078-0432.CCR-16-1761","article-title":"PD-L2 expression in human tumors: relevance to Anti-PD-1 therapy in cancer","volume":"23","author":"Yearley","year":"2017","journal-title":"Clin Cancer Res"},{"key":"2025071710064095000_CIT0011","doi-asserted-by":"publisher","first-page":"2052","DOI":"10.1093\/annonc\/mdy264","article-title":"Phase III, randomised trial of avelumab versus physician\u2019s choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300","volume":"29","author":"Bang","year":"2018","journal-title":"Ann Oncol"},{"key":"2025071710064095000_CIT0012","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1200\/JCO.20.00892","article-title":"Phase III trial of avelumab maintenance after First-Line induction chemotherapy versus continuation of chemotherapy in patients with gastric cancers: results from JAVELIN gastric 100","volume":"39","author":"Moehler","year":"2021","journal-title":"J Clin Oncol"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/oncolo\/advance-article-pdf\/doi\/10.1093\/oncolo\/oyaf195\/63593545\/oyaf195.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/30\/7\/oyaf195\/63593545\/oyaf195.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/30\/7\/oyaf195\/63593545\/oyaf195.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T14:06:46Z","timestamp":1752761206000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/doi\/10.1093\/oncolo\/oyaf195\/8175229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":12,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7,4]]}},"URL":"https:\/\/doi.org\/10.1093\/oncolo\/oyaf195","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"type":"print","value":"1083-7159"},{"type":"electronic","value":"1549-490X"}],"subject":[],"published-other":{"date-parts":[[2025,7]]},"published":{"date-parts":[[2025,7]]},"article-number":"oyaf195"}}