Clinical Trial

. 2025 Jul;21(17):2135-2141.

doi: 10.1080/14796694.2025.2514935. Epub 2025 Jun 6.

A multicenter Phase II study of mFOLFOX6 plus nivolumab for gastric cancer with severe peritoneal metastases: WJOG16322G

Munehiro Wakabayashi^{1

2}, Toshiki Masuishi¹, Takatsugu Ogata³, Fumiyasu Hanamura⁴, Mitsuhiro Furuta⁵, Yoshiyuki Yamamoto⁶, Kentaro Kawakami⁷, Hidekazu Hirano⁸, Yosuke Kito⁹, Naoki Izawa¹⁰, Naoki Takahashi¹¹, Toshihiko Matsumoto¹², Hisato Kawakami¹³, Takayuki Ando¹⁴, Keiko Minashi¹⁵, Chiho Kudo¹⁶, Kenichi Yoshimura¹⁷, Kei Muro¹

Affiliations

¹ Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
² Department of Gastroenterology and Hepatology, Faculty of Medicine, Toho University, Tokyo, Japan.
³ Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Japan.
⁴ Department of Medical Oncology, Hamanomachi Hospital, Fukuoka, Japan.
⁵ Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan.
⁶ Department of Gastroenterology, University of Tsukuba Hospital, Tsukuba, Japan.
⁷ Department of Medical Oncology, Keiyukai Sapporo Hospital, Sapporo, Japan.
⁸ Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁹ Department of Medical Oncology, Ishikawa Prefectural Central Hospital, Ishikawa, Japan.
¹⁰ Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan.
¹¹ Department of Gastroenterology, Saitama Cancer Center Hospital, Saitama, Japan.
¹² Department of Medical Oncology, Ichinomiyanishi Hospital, Ichinomiya, Japan.
¹³ Department of Medical Oncology, Faculty of Medicine, Kindai University, Osaka, Japan.
¹⁴ Third Department of Internal Medicine, University of Toyama, Toyama, Japan.
¹⁵ Clinical Trial Promotion Department, Chiba Cancer Center, Chiba, Japan.
¹⁶ Department of Clinical Research Support Section, Aichi Cancer Center Hospital, Nagoya, Japan.
¹⁷ Center for Integrated Medical Research, Hiroshima University Hospital, Hiroshima University, Hiroshima, Japan.

PMID: 40476844
PMCID: PMC12239818
DOI: 10.1080/14796694.2025.2514935

Clinical Trial

A multicenter Phase II study of mFOLFOX6 plus nivolumab for gastric cancer with severe peritoneal metastases: WJOG16322G

Munehiro Wakabayashi et al. Future Oncol. 2025 Jul.

. 2025 Jul;21(17):2135-2141.

doi: 10.1080/14796694.2025.2514935. Epub 2025 Jun 6.

Authors

Affiliations

¹ Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
² Department of Gastroenterology and Hepatology, Faculty of Medicine, Toho University, Tokyo, Japan.
³ Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Japan.
⁴ Department of Medical Oncology, Hamanomachi Hospital, Fukuoka, Japan.
⁵ Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan.
⁶ Department of Gastroenterology, University of Tsukuba Hospital, Tsukuba, Japan.
⁷ Department of Medical Oncology, Keiyukai Sapporo Hospital, Sapporo, Japan.
⁸ Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁹ Department of Medical Oncology, Ishikawa Prefectural Central Hospital, Ishikawa, Japan.
¹⁰ Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan.
¹¹ Department of Gastroenterology, Saitama Cancer Center Hospital, Saitama, Japan.
¹² Department of Medical Oncology, Ichinomiyanishi Hospital, Ichinomiya, Japan.
¹³ Department of Medical Oncology, Faculty of Medicine, Kindai University, Osaka, Japan.
¹⁴ Third Department of Internal Medicine, University of Toyama, Toyama, Japan.
¹⁵ Clinical Trial Promotion Department, Chiba Cancer Center, Chiba, Japan.
¹⁶ Department of Clinical Research Support Section, Aichi Cancer Center Hospital, Nagoya, Japan.
¹⁷ Center for Integrated Medical Research, Hiroshima University Hospital, Hiroshima University, Hiroshima, Japan.

PMID: 40476844
PMCID: PMC12239818
DOI: 10.1080/14796694.2025.2514935

Abstract

Advanced gastric cancer (AGC) patients with severe peritoneal metastases (SPM), characterized by massive ascites and/or inadequate oral intake, have a poor prognosis with the median overall survival of around 7 months, even when treated with fluorouracil/l-leucovorin plus oxaliplatin (mFOLFOX6), despite being a treatment options for these patients demonstrated in the WJOG10517G study. However, these patients were excluded from pivotal Phase III trials, including the CheckMate 649 study, which demonstrated the benefit of adding nivolumab to mFOLFOX6, due to tumor-related complications. Given the lack of data on the efficacy and safety of combining nivolumab with mFOLFOX6 for AGC patients with SPM, we initiated a Phase II study to evaluate this combination. The primary endpoint was the 1-year survival rate.Clinical trial registration: Japan Registry of Clinical Trials (jRCTs) 041220164.

Keywords: Gastric cancer; inadequate oral intake; mFOLFOX6 plus nivolumab; massive ascites; severe peritoneal metastases.

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Conflict of interest statement

Munehiro Wakabayashi reports honoraria from Daiichi-Sankyo Co., Ltd, Ono Pharmaceutical Co., Ltd. Toshiki Masuishi reports honoraria from Bayer Yakuhin Co., Ltd, Bristol-Myers Squibb Co., Ltd, Chugai Pharmaceutical Co., Ltd, Daiichi-Sankyo Co., Ltd, Eli Lilly Co., Ltd, Merck Serono Co., Ltd, Ono Pharmaceutical Co., Ltd, Sanofi Co., Ltd, Taiho Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd, Yakult Honsha Co., Ltd, MSD Co., Ltd, Takata Co., Ltd, Astellas Co., Ltd, Guardant Health Co., Ltd, and Nippon Kayaku Co., Ltd, and research funding from Amgen Co., Ltd, Boehringer Ingelheim Co., Ltd, CMIC Co., Ltd, Daiichi-Sankyo Co., Ltd, Eli Lilly Japan Co., Ltd, MSD Co., Ltd, Novartis Co., Ltd, Ono Pharmaceutical Co., Ltd, Pfizer Co., Ltd, Syneos Health Co., Ltd. Takatsugu Ogata reports honoraria from Ono Pharmaceutical Co., Ltd, Bristol-Myers Squibb Co., Ltd, Taiho Pharmaceutical Co., Ltd, MSD Co., Ltd, Astellas Pharmaceutical Co., Ltd. Fumiyasu Hanamura reports honoraria from Daiichi-Sankyo Co., Ltd, Taiho Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd, MSD Co., Ltd, and consulting or advisory role in Daiichi-Sankyo Co., Ltd. Mitsuhiro Furuta reports honoraria from Astellas Pharmaceutical Co., Ltd, Bristol-Myers Squibb Co., Ltd, Eli Lilly Co., Ltd, Merck Bio Pharma Co., Ltd, Ono Pharmaceutical Co., Ltd. Hidekazu Hirano reports honoraria from Novartis Co., Ltd, Ono Pharmaceutical Co., Ltd, Taiho Pharmaceutical Co., Ltd, Bristol-Myers Squibb Co., Ltd, and research funding from PPD, Daiichi-Sankyo Co., Ltd, Nippon Boehringer Ingelheim Co., Ltd, ALX Oncology Co., Ltd, BeiGene Co., Ltd, Novartis Co., Ltd, Amgen Co., Ltd, Bristol-Myers Squibb Co., Ltd, Taiho Pharmaceutical Co., Ltd. Yosuke Kito reports honoraria from Ono Pharmaceutical Co., Ltd, Taiho Pharmaceutical Co., Ltd, Daiichi-Sankyo Co., Ltd, Chugai Pharmaceutical Co., Ltd. Naoki Izawa reports honoraria from Taiho Pharmaceutical Co., Ltd, Bristol-Myers Squibb Co., Ltd, Daiichi-Sankyo Co., Ltd, MSD Oncology Co., Ltd, Sysmex Co., Ltd, AstraZeneca Co., Ltd, Nippon Kayaku Co., Ltd, Merck Serono Co., Ltd, and research funding from Taiho Pharmaceutical Co., Ltd. Naoki Takahashi reports honoraria from Ono Pharmaceutical Co., Ltd, Taiho Pharmaceutical Co., Ltd, Bristol-Myers Squibb Co., Ltd. Toshihiko Matsumoto reports honoraria from Bayer Co., Ltd, Bristol-Myers Squibb Co., Ltd, Chugai Pharmaceutical Co., Ltd, Daiichi Sankyo Co., Ltd, Eli Lilly Japan Co., Ltd, Merck Bio Pharma Co., Ltd, MSD Co., Ltd, Ono Pharmaceutical Co., Ltd, Sanofi Co., Ltd, Taiho Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd, Astellas Pharmaceutical Co., Ltd and Yakult Honsha Co., Ltd, and research funding from Daiichi Sankyo Co., Ltd, Astellas Pharmaceutical Co., Ltd, Sanofi Co., Ltd. Hisato Kawakami reports honoraria from Bristol-Myers Squibb Co., Ltd, Ono Pharmaceutical Co., Ltd, Daiichi Sankyo Co., Ltd, MSD Co., Ltd, Taiho Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd, Novartis Co., Ltd, Astellas Pharmaceutical Co., Ltd and research funding from Daiichi Sankyo Co., Ltd, Astellas Pharmaceutical Co., Ltd, Eisai. Co., Ltd, Bristol-Myers Squibb Co., Ltd, Kobayashi Pharmaceutical Co., Ltd, Taiho Pharmaceutical Co., Ltd. Takayuki Ando reports honoraria from Daiichi Sankyo Co., Ltd, Eli Lilly Japan Co., Ltd, Bristol-Myers Squibb Co., Ltd, Ono Pharmaceutical Co., Ltd, Taiho Pharmaceutical Co., Ltd, MSD Co., Ltd, Astellas Pharmaceutical Co., Ltd. Keiko Minashi reports research funding from Astellas Pharmaceutical Co., Ltd, Taiho Pharmaceutical Co., Ltd, Amgen Co., Ltd, Daiichi Sankyo Co., Ltd, MSD Co., Ltd, PPD-SNBL K.K. Kei Muro reports honoraria from MSD Co., Ltd, Bristol-Myers Squibb Co., Ltd, Ono Pharmaceutical Co., Ltd, Eli Lilly Co., Ltd, Takeda Pharmaceutical Co., Ltd, Daiichi Sankyo Co., Ltd, Taiho Pharmaceutical Co., Ltd, and research funding from Astellas Pharmaceutical Co., Ltd, Amgen Co., Ltd, Sanofi Co., Ltd, Novartis Co., Ltd, Parexel International, PRA Health Sciences, Taiho Pharmaceutical Co., MSD Co., Ltd, Chugai Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd, and consulting or advisory role in Amgen Co., Ltd, Astellas Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd, AstraZeneca Co., Ltd, Chugai Pharmaceutical Co., Ltd, and plays advisory role in Astellas Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd, Amgen Co., Ltd, AstraZeneca Co., Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

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References

1. Jungian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-esophageal junction, and esophageal adenocarcinoma (CheckMate 649): a randomized, open-label, phase 3 trial. Lancet. 2021;398(10294):27–40. doi: 10.1016/S0140-6736(21)00797-2 - DOI - PMC - PubMed
1. Eguchi Nakajima T, Yamaguchi K, Boku N, et al. Randomized phase II/III study of 5-fluorouracil/l-leucovorin plus paclitaxel administered to patients with severe peritoneal metastases of gastric cancer (JCOG1108/WJOG7312G). Gastric Cancer. 2020;23(4):677–688. doi: 10.1007/s10120-020-01043-x - DOI - PubMed
2. •• The first prospective Phase II/III study for gastric cancer patients with severe peritoneal metastases demonstrated that chemotherapy is indicated for these patients, and 5-fluorouracil (5-FU)/l-leucovorin (l-LV) plus paclitaxel might be preferred over 5- FU/l-LV alone.
1. Masuishi T, Kadowaki S, Kondo M, et al. FOLFOX as first-line therapy for gastric cancer with severe peritoneal metastasis. Anticancer Res. 2017;37(12):7037–7042. - PubMed
2. • A retrospective study showed that modified FOLFOX6 for gastric cancer patients with severe peritoneal metastases had good efficacy, resulting in improvement in ascites and oral intake.
1. Masuishi T, Nakajima Eguchi T, Yamazaki K, et al. WJOG10517G: a multicenter phase II study of mFOLFOX6 in gastric cancer patients with severe peritoneal metastases. Future Oncol. 2020;16(20):1417–1424. doi: 10.2217/fon-2020-0298 - DOI - PubMed
2. • A protocol paper from WJOG10517G prospectively evaluated the efficacy and safety of mFOLFOX6 in advanced gastric cancer patients with severe peritoneal metastases.
1. Hara H, Masuishi T, Ando T, et al. A multicenter phase II study of mFOLFOX6 in advanced gastric cancer patients with severe peritoneal metastases: WJOG10517G. Ann Oncol. 2022;33(suppl 4):s284–s285. doi: 10.1016/j.annonc.2022.04.189 - DOI
2. •• A multicenter Phase II study for gastric cancer patients with severe peritoneal metastases showed that mFOLFOX6 could be safely administered and achieved improvements in ascites and oral intake, with certain anti-tumor effect.

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A multicenter Phase II study of mFOLFOX6 plus nivolumab for gastric cancer with severe peritoneal metastases: WJOG16322G

Affiliations

A multicenter Phase II study of mFOLFOX6 plus nivolumab for gastric cancer with severe peritoneal metastases: WJOG16322G

Authors

Affiliations

Abstract

Conflict of interest statement

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References

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Supplementary concepts

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Full Text Sources

Medical