WJOG18524G: a single-arm phase II study evaluating bemarituzumab combined with ramucirumab and paclitaxel in fibroblast growth factor receptor 2b (FGFR2b)-positive advanced gastric or gastroesophageal junction cancer (RAINBIRD)

K Shimozaki; K Hirata; H Hayashi; Y Sato; Y Komatsu; S Taniguchi; N Takahashi; K Yamaguchi; M Furuta; T Kawakami; Y Narita; T Ando; A Makiyama; S Mitani; T Ogata; N Takegawa; W Okamoto; T Nishina; M Komoda; A Hosokawa; N Boku; H Kawakami; K Yamazaki; K Muro

doi:10.1016/j.esmogo.2025.100189

WJOG18524G: a single-arm phase II study evaluating bemarituzumab combined with ramucirumab and paclitaxel in fibroblast growth factor receptor 2b (FGFR2b)-positive advanced gastric or gastroesophageal junction cancer (RAINBIRD)

ESMO Gastrointest Oncol. 2025 Jun 9:9:100189. doi: 10.1016/j.esmogo.2025.100189. eCollection 2025 Sep.

Authors

K Shimozaki¹, K Hirata², H Hayashi², Y Sato³, Y Komatsu⁴, S Taniguchi⁵, N Takahashi⁶, K Yamaguchi¹, M Furuta⁷, T Kawakami⁸, Y Narita⁹, T Ando¹⁰, A Makiyama¹¹, S Mitani¹², T Ogata¹³, N Takegawa¹⁴, W Okamoto¹⁵, T Nishina¹⁶, M Komoda¹⁷, A Hosokawa¹⁸, N Boku¹⁹, H Kawakami⁵, K Yamazaki⁸, K Muro⁹

Affiliations

¹ Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo.
² Keio Cancer Center, Keio University School of Medicine, Tokyo.
³ Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo.
⁴ Division of Cancer Center, Hokkaido University Hospital, Sapporo.
⁵ Department of Medical Oncology, Tohoku University Hospital, Sendai.
⁶ Department of Gastroenterology, Saitama Cancer Center, Saitama.
⁷ Department of Gastroenterology, Kanagawa Cancer Center, Yokohama.
⁸ Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka.
⁹ Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya.
¹⁰ Third Department of Internal Medicine, University of Toyama, Toyama.
¹¹ Cancer Center, Gifu University Hospital, Gifu.
¹² Department of Medical Oncology, Kindai University Faculty of Medicine, Osakasayama.
¹³ Department of Clinical Oncology, Osaka International Cancer Institute, Osaka.
¹⁴ Department of Gastroenterology, Hyogo Cancer Center, Hyogo.
¹⁵ Department of Clinical Oncology, Hiroshima University Hospital, Hiroshima.
¹⁶ Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama.
¹⁷ Department of Gastrointestinal and Medical Oncology, NHO Kyushu Cancer Center, Fukuoka.
¹⁸ Department of Clinical Oncology, University of Miyazaki Hospital, Miyazaki.
¹⁹ Department of Oncology and General Medicine, IMSUT Hospital, Institute of Medical Science, University of Tokyo, Japan.

Abstract

Background: Fibroblast growth factor receptor 2b (FGFR2)-overexpressing advanced gastric cancer (AGC) is associated with poor prognosis and limited treatment options. Bemarituzumab, which selectively binds to FGFR2b, is being investigated in combination with chemotherapy as a first-line treatment. Dual inhibition of the vascular endothelial growth factor-vascular endothelial growth factor receptor and FGF-FGFR pathways may improve the survival of FGFR2b-positive AGC through synergistic inhibition of angiogenesis and the downstream signals for tumor proliferation.

Design: The WJOG18524G trial (RAINBIRD) is a single-arm, multicenter phase II trial to evaluate the safety and efficacy of bemarituzumab in combination with paclitaxel plus ramucirumab in patients with FGFR2b-positive AGC who are intolerant or refractory to first-line fluoropyrimidine-based chemotherapy. The main inclusion criteria are unresectable or metastatic FGFR2b-positive gastric adenocarcinoma, refractoriness or intolerance to fluoropyrimidine-based chemotherapy, measurable lesions, and performance status of 0 or 1. The primary endpoint is the objective response rate, which is assessed by a blinded independent central review. Translational research is planned to explore the predictive biomarkers and mechanisms of resistance to bemarituzumab by sequencing tumor DNA (PleSSiSion-Neo) and circulating tumor DNA (Guardant360), which are collected at multiple time points.

Keywords: FGFR2b; bemarituzumab; gastric cancer.