Abstract 1259TiP
Background
Microsatellite instability-high (MSI-H) is an established biomarker for response to immune checkpoint inhibitors (ICIs). ICIs in combination with chemotherapy consisting of fluoropyrimidine and oxaliplatin can be administered in the first-line setting for gastric cancer (GC). However, evidence suggests that MSI-H tumors are responsive to nivolumab plus ipilimumab but are less responsive to such cytotoxic chemotherapy, and that nivolumab plus low-dose ipilimumab can improve survival with acceptable safety in MSI-H colorectal cancer. Collectively, we plan to investigate the efficacy and safety of nivolumab plus low-dose ipilimumab for MSI-H GC, which accounts for ∼5% of all GC cases.
Trial design
NO LIMIT (WJOG13320G/CA209-7W7) is an investigator-initiated, single-arm, open-label, 14-center phase II trial of NIVO plus low-dose IPI for MSI-H GC in the first-line setting. Eligibility criteria include unresectable advanced, recurrent, or metastatic gastric or esophagogastric junction cancer with a histologically confirmed diagnosis of adenocarcinoma; confirmed MSI-H status with the MSI-IVD Kit (FALCO); no prior systemic anticancer therapy; an Eastern Cooperative Oncology Group performance status of 0 or 1; and a measurable lesion per RECIST 1.1. The primary objective of the study is to determine the overall response rate (ORR) for the NIVO+IPI regimen as assessed by blinded independent central review. Secondary endpoints include progression-free survival, overall survival, duration of response, safety, tolerability, and biomarkers. The number of patients was set at 28 based on the threshold and expected ORR values of 35 and 65%, respectively, with a one-sided alpha error of 0.025 and power of 0.80. Subjects will receive treatment with nivolumab (240 mg) biweekly in combination with ipilimumab (1 mg/kg) every 6 weeks. NO LIMIT study began enrolling patients in November 2020 and is ongoing in Japan. As of April 2022, 22 of the planned 28 patients have been enrolled.
Clinical trial identification
JapicCTI-205400.
Editorial acknowledgement
Legal entity responsible for the study
West Japan Oncology Group.
Funding
Bristol-Myers Squibb Co. Ltd.
Disclosure
H. Kawakami: Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb Co. Ltd., Bayer Yakuhin Ltd, Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co. Ltd, Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo 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: Glaxo Smith Kline 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 HEALTHSCIENCES, 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, Takeda Pharmaceutical Co.,Ltd., GlaxoSmithKline K.K., Sanofi K.K., Chugai Pharmaceutical Co.,Ltd., Nippon Boehringer Ingelheim Co.,Ltd., Sysmex Corporation, Medical Reserch Support, Eli Lilly Japan K.K., Amgen Inc., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., SRL, Inc., Daiichi Sankyo Co., Ltd.. S. Kadowaki: Financial Interests, Personal and Institutional, Research Grant: Taiho, Eli Lilly, MSD, Ono, Daichi Sankyo; Financial Interests, Institutional, Research Grant: Chugai, Nobelpharma, Yansen; Financial Interests, Personal, Invited Speaker: BMS, Bayer, Merck Serono, Eisai. K. Hirata: Financial Interests, Personal, Research Grant: Taiho Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb Company, EA Pharma Co., Ltd, Pfizer Inc.; 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.. T. Esaki: Financial Interests, Personal, Invited Speaker: Chugai, Taiho, EP force, MSD, Daiichi Sankyo, Eli Lilly, Ono; Financial Interests, Institutional, Research Grant: MSD, Novartis, Ono, Nihon Kayaku, IQVIA, Daiichi Sankyo, Chugai, Syneos Health Clinical, Pfizer, Dainippon Sumitomo, Qluintiles, Eli Lilly, Parexel, Astellas, Astellas Amgen Biopharma, Taiho, Chugai, Nihon Kayaku. N. Sugimoto: Financial Interests, Institutional, Funding: MSD, Ono Pharmaceutical, Taiho Pharmaceutical, Eli Lilly Japan, Dai-ichi Sankyo, Danippon Sumitomo Pharma, Chugai Pharma, BeiGene, Solasia Pharma, Astellas Pharma, Eisai. A. Makiyama: Financial Interests, Personal, Invited Speaker: Lilly Japan, Chugai Pharma, Takeda, Daiichi Sankyo, Taiho Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb Japan. N. Machida: Financial Interests, Personal, Speaker’s Bureau: Ono, BMS, Taiho, MSD, Daiichi-Sankyo, Lilly, Yakult, Takeda; Financial Interests, Institutional, Principal Investigator: Ono, BMS, MSD, Daiichi-Sankyo, AstraZeneca, Amgen. H. Hirano: Other, Institutional, Funding, Research fund: BeiGene. H. Hara: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb, Boehringer Ingelheim, Dainippon Sumitomo; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, MSD, Ono, Bayer, Chugai, Kyowa Hakko Kirin, Lilly, Merck Biopharma, Sanofi, Taiho, Takeda, Yakult; Financial Interests, Institutional, Invited Speaker: Amgen, Astellas, AstraZeneca, Bayel, BeiGene, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Janssen, Merck Biopharma, MSD, Ono, Taiho. T. Kawakami: Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical, Bristol-Myers Squibb. W. Okamoto: Financial Interests, Personal, Invited Speaker: Chugai Pharma, Ono Pharmaceutical, Bristol-Myers Squibb Japan, Yakult Honsha, Lilly Japan, Thermo Fisher Scientific, Takeda, Novartis, Taiho Pharmaceutical; Financial Interests, Personal, Expert Testimony, 03/2022: Daiichi-Sankyo; Financial Interests, Institutional, Invited Speaker: Janssen Oncology. Y. Komatsu: Non-Financial Interests, Institutional, Research Grant: Ono, Daiichi-Sankyo, Taiho, Chugai; Financial Interests, Personal, Speaker’s Bureau: Ono, Taiho, Chugai, Lilly, bayer. S. Hironaka: Financial Interests, Personal, Speaker’s Bureau: Ono pharmaceutical, Eli Lilly, Chugai phamaceutical, Merck biopharma, Taiho pharmaceutical, Daiichi Sankyo, Bristol-Myers Squibb, MSD K.K., Yakult Honsha, AstraZeneca, Sanofi. K. Muro: Financial Interests, Institutional, Research Grant: Astellas, Amgen, Solasia Pharma, Sanofi, Daichi Sankyo, Taiho, MSD, Parexel Internatinonal, Merck KGaA, Pfizer, Eisai, Ono; Financial Interests, Personal and Institutional, Advisory Board: Amgen, AstraZeneca, Ono, Chugai; Financial Interests, Personal, Speaker’s Bureau: Daiichi Snakyo, Taiho, Ono, Bristol-Myers Squibb; Non-Financial Interests, Personal, Principal Investigator: Takeda. All other authors have declared no conflicts of interest.