Phase II study of avelumab and trastuzumab with FOLFOX chemotherapy in previously untreated HER2-amplified metastatic gastroesophageal adenocarcinoma

Abstract Background 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 o...

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Veröffentlicht in:The oncologist (Dayton, Ohio) Jg. 30; H. 7
Hauptverfasser: Lee, Michael S, Chao, Joseph, Mulcahy, Mary F, Kasi, Pashtoon M, Alistar, Angela T, Mukherjee, Sarbajit, Akce, Mehmet, Moore, Dominic T, McRee, Autumn J, Somasundaram, Ashwin
Format: Journal Article
Sprache:Englisch
Veröffentlicht: US Oxford University Press 01.07.2025
Schlagworte:
Adenocarcinoma
Adenocarcinoma - drug therapy
Adenocarcinoma - genetics
Adenocarcinoma - pathology
Adult
Aged
Antibodies, Monoclonal, Humanized - administration & dosage
Antibodies, Monoclonal, Humanized - pharmacology
Antibodies, Monoclonal, Humanized - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Cancer
Care and treatment
Chemotherapy
Clinical Trial Results
Drug therapy
Esophageal cancer
Esophageal Neoplasms - drug therapy
Esophageal Neoplasms - genetics
Esophageal Neoplasms - pathology
Female
Fluorouracil - pharmacology
Fluorouracil - therapeutic use
Humans
Leucovorin - pharmacology
Leucovorin - therapeutic use
Male
Middle Aged
Organoplatinum Compounds - pharmacology
Organoplatinum Compounds - therapeutic use
Pharmacology, Experimental
Physiological aspects
Receptor, ErbB-2 - genetics
Stomach cancer
Stomach Neoplasms - drug therapy
Stomach Neoplasms - genetics
Stomach Neoplasms - pathology
Trastuzumab - administration & dosage
Trastuzumab - pharmacology
Trastuzumab - therapeutic use
United States
trastuzumab
esophageal cancer
gastric cancer
HER2
immunotherapy
ISSN:1083-7159, 1549-490X, 1549-490X
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Zusammenfassung:Abstract Background 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. Methods 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 + trastuzumab. The study was initially designed as a Simon’s 2-stage trial, but enrollment was stopped after the 18-subject first stage for reasons unrelated to safety or efficacy. Results 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. Conclusions 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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1083-7159
1549-490X
1549-490X
DOI:10.1093/oncolo/oyaf195