Abstract 497TiP
Background
Trifluridine/tipiracil (FTD/TPI) prolongs overall survival (OS) as the third- or later-line treatment in patients with advanced gastric cancer (GC) and gastroesophageal junction (GEJ) adenocarcinoma, whereas the efficacy of FTD/TPI monotherapy is limited (objective response rate [ORR]: 4%, median progression-free survival [PFS]: 2.0 months). Recently, a single-arm phase II trial of FTD/TPI plus ramucirumab (RAM) showed the promising activity (ORR: 16%, median PFS: 5.3 months) in third- or later line treatment of advanced GC and GEJ cancer (Kawazoe A et al. Lancet Gastroenterol Hepatol. 2021). There have been no clinical trials to directly compare FTD/TPI plus RAM with FTD/TPI monotherapy in patients with advanced GC and GEJ adenocarcinoma.
Trial design
The RETRIEVE trial (WJOG15822G) is an open-label, multi-center, randomized phase II trial comparing FTD/TPI plus RAM with FTD/TPI monotherapy in the third- or later-line setting. Eligibility criteria include age of > 20 years; performance status (PS) of 0 or 1; unresectable or recurrent ＧＣ or GEJ adenocarcinoma; confirmed HER2 status; refractory or intolerant to fluoropyrimidine, taxane or irinotecan; refractory to RAM (not intolerant); and at least a measurable lesion per RECIST 1.1. Patients are randomized to FTD/TPI (35 mg/m2 twice daily, evening of Day 1 to morning of Day 6 and evening of Day 8 to morning of Day 13, every 4 weeks) or FTD/TPI plus RAM (8 mg/kg, every 2 weeks). Stratification factors are ECOG PS, the timing of previous use of RAM, and nivolumab. The primary endpoint is PFS, and the secondary endpoints are OS, ORR, disease control rate, and safety. The expected hazard ratio of PFS was set as 0.7, assuming 4-month PFS rate of 27% and 40%, with a one-sided alpha error of 0.10 and power of 0.70. The required number of subjects is 110 in total. This trial was registered at the Japan Registry of Clinical Trials (jRCT) as study number jRCT041220120. This trial started on January 21, 2023. This clinical trial is funded by Taiho Pharmaceutical Co. Ltd.
Legal entity responsible for the study
West Japan Oncology Group.
Funding
Taiho Pharmaceutical Co. Ltd.
Disclosure
N. Takahashi: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical co. ltd, Bristol Myers Squibb, Ono Pharmaceutical co. ltd. H. Hara: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Boehringer Ingelheim, MSD; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, MSD, Ono, Bayer, Chugai, Lilly, Merck Biopharma, Taiho, Takeda, Yakult, Bristol Myers Squibb, Miyarisan; Financial Interests, Institutional, Invited Speaker: Amgen, Astellas, AstraZeneca, Bayer, BeiGene, Chugai, Daiichi Sankyo, Janssen, Merck Biopharma, MSD, Ono, Taiho, ALX Oncology, Jazz Pharmaceuticals. K. Nagashima: Financial Interests, Personal, Other, Received consulting fees: Senju Pharmaceutical Co., Ltd., Toray Industries, Inc., Kowa Company, Ltd.; Financial Interests, Institutional, Other, Received consulting fees: Eli Lilly. K. Hirata: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan K.K., Taiho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb Company, Yakult Honsha Co., Ltd.; Financial Interests, Personal and Institutional, Research Grant: Taiho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb Company, Pfizer Inc. T. Masuishi: Financial Interests, Personal, Invited Speaker: Takeda, Chugai, Merck Bio Pharma, Taiho, Bayer, Eli Lilly, Yakult Honsha, Sanofi, Daiichi Sankyo, Ono, Bristol Myers Squibb, MSD, Nippon Kayaku; Financial Interests, Institutional, Funding: Daiichi Sankyo, Ono, Novartis, Amgen, Syneos Healthe Clinical, Boehringer Ingelheim, Pfizer, Cimic Shift Zero, Eli Lilly. T. Matsumoto: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., Bayer Co., Ltd., Bristol Myers Squibb Co., Ltd., Daiichi Sankyo Co., Ltd., Eli Lilly Japan Co., Ltd., Merck Bio Pharma Co., Ltd., MSD Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Co., Ltd. H. Kawakami: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb Co. Ltd., Ono Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Bayer Yakuhin Ltd., Eli Lilly Japan K.K., MSD K.K., Chugai Pharmaceutical Co. Ltd., Merck Biopharma Co., Ltd., Takeda Pharmaceutical Co. Ltd., Yakult Pharmaceutical Industry, Teijin Pharma Ltd., Taiho Pharmaceutical Co. Ltd.; Financial Interests, Personal, Advisory Board: Daiichi Sankyo Co. Ltd.; Financial Interests, Personal, Other, Lecture: GSK K.K, Otsuka Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Research Grant, Investigator-Initiated Trial: Bristol Myers Squibb Co. Ltd.; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical Co. Ltd., Eisai Co., Ltd., Kobayashi Pharmaceutical Co. Ltd., PAREXEL International Corp., PRA Health Sciences, EPS Corporation., Kissei Pharmaceutical Co., Ltd., EPS International Co., Ltd., MSD K.K., Ono Pharmaceutical Co., Ltd., PPD-SNBL K.K, SymBio Pharmaceuticals Limited., IQVIA Services JAPAN K.K., Syneos Health Clinical K.K., Nippon Kayaku Co., Ltd., EP-CRSU Co., Ltd., Mebix, Inc., Bristol Myers Squibb K.K., Janssen Pharmaceutical K.K., Eisai Co., Ltd., AstraZeneca K.K., Mochida Pharmaceutical Co., Ltd., Covance Japan Inc., Japan Clinical Research Operations, Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., GSK K.K., Sanofi K.K., Nippon Boehringer Ingelheim Co., Ltd., Sysmex Corporation, Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., SRL, Inc., Daiichi Sankyo Co., Ltd., Amgen Inc., Medical Research Support, Eli Lilly Japan K.K. K. Yamazaki: Financial Interests, Personal, Invited Speaker: Chugai Pharma, Daiichi Sankyo, Yakult Honsha, Takeda, Bayer, Merck Serono, Taiho Pharmaceutical, Lilly, Sanofi, Ono Pharmaceutical, MSD, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical. S. Hironaka: Financial Interests, Personal, Other, lecture: Ono Pharmaceutical, BMS, Eli Lilly, Taiho, Daiichi Sankyo, MSD, Chugai, Merck Biopharma, Takeda, Yakult Honsha. N. Boku: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Eli Lily, Ono Pharmaceutical, Taiho Pharma, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Takeda Pharmaceutical, ONO Pharmaceutical. K. Muro: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Ono, Chugai; Financial Interests, Personal, Invited Speaker: Eli Lilly, Ono, Daiichi Sankyo, Taiho, Bristol Myers Squibb, Takeda, Chugai, AstraZeneca, Amgen; Financial Interests, Institutional, Research Grant, Including local PI as role: Astellas, Amgen, Sanofi, Daiichi Sankyo, Taiho, MSD, Pfizer, Merck Biopharma, Eisai, Ono, Novartis; Non-Financial Interests, Principal Investigator: Takeda.