1513MO - A phase II study of nivolumab plus low dose ipilimumab as first -line therapy in patients with advanced gastric or esophago-gastric junction MSI-H tumor: First results of the NO LIMIT study (WJOG13320G/CA209-7W7)

Background

Microsatellite instability-high (MSI-H) is an established biomarker for response to immune checkpoint inhibitors. Herein, we report the efficacy and safety of nivolumab plus low-dose ipilimumab as first-line therapy in MSI-H advanced gastric or esophagogastric junction cancer (GC) patients from the phase II study.

Methods

Eligible patients were unresectable advanced, recurrent, or metastatic GC with a histologically confirmed diagnosis of adenocarcinoma; confirmed MSI-H status with the MSI-IVD Kit (FALCO); no prior systemic anticancer therapy given as primary therapy for advanced or metastatic disease. Nivolumab (240 mg) biweekly and ipilimumab (1 mg/kg) every six weeks were given until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR) assessed by a blinded independent central review (BICR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and safety.

Results

Between November 2020 and Aug 2022, 29 patients were enrolled from 935 screened cases. The median age was 75 (range 54-84), and 44.8% of patients were male. At the data cut-off (December 12, 2022), 3 and 15 patients achieved confirmed complete and partial responses with ORR of 62.1% (95% CI: 42.3-79.3). The DCR was 79.3% (95% CI, 60.3-92.0). With the median follow-up of 9.0 months (range, 4.0-18.0), the median PFS was 13.8 (95% CI, 13.7-NR) months, and median DOR and OS were not reached yet. 12-month PFS and OS rates yielded 73% (95% CI, 52-86) and 80% (95% CI, 57-91), respectively. The most common reason for treatment discontinuation was adverse events. The safety profile was consistent with the known profiles of nivolumab plus low dose ipilimumab, and there were no unexpected safety signals. Treatment-related death was not observed.

Conclusions

The chemo-free strategy with a combination of nivolumab and low-dose ipilimumab demonstrated high and robust efficacy with good tolerability in MSI-H GC patients.

Clinical trial identification

jRCT2080225304.

Editorial acknowledgement

Legal entity responsible for the study

West Japan Oncology Group.

Funding

Bristol Meyers Squibb.

Disclosure

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. 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. S. Kadowaki: Financial Interests, Personal, Invited Speaker: Taiho, MSD, Ono, Daiichi Sankyo, BMS, Bayer, Merck, Eisai, Otsuka; Financial Interests, Institutional, Funding: Eli Lilly, MSD, Ono, Daiichi Sankyo, Chugai, NOBEL Pharma, Janssen. A. Makiyama: Financial Interests, Personal, Invited Speaker: Eli Lilly, Taiho, Ono, Daiichi Sankyo, Bristol Myers Squibb. 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. N. Sugimoto: Financial Interests, Institutional, Invited Speaker: Eli Lilly, MSD, Pfizer, Daiichi Sankyo, Seagen, Ono. N. Machida: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Ono, Taiho, MSD, Daiichi Sankyo, Yakult, Eli Lilly Japan, Chugai, Astellas, Takeda, Merck, Nichi-Iko, Nippon Kayaku; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Ono, Daiichi Sankyo, Astellas, MSD, Amgen, ALX Oncology, Seagen. 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; Financial Interests, Institutional, Invited Speaker: Amgen, Astellas, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Janssen, Merck Biopharma, MSD, Ono, Taiho, ALX oncology. H. Hirano: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Ono Pharmaceutical, Teijin Pharma, Nichi-Iko, Novartis; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Ono Pharmaceutical, Janssen Pharmaceutical, Merck Biopharma, Bristol Myers Squibb, Pfizer, Eisai, Amgen, Astellas, Seagen, MSD, Incyte, BeiGene, Novartis. T. Esaki: Financial Interests, Personal, Invited Speaker: Chugai, Taiho, EP force, MSD, Daiichi Sankyo, Eli Lilly, Ono, Bristol; Financial Interests, Institutional, Research Grant: MSD, Novartis, Ono, Nihon Kayaku, IQVIA, Daiichi Sankyo, Chugai, Syneos Health Clinical, Pfizer, Dainippon Sumitomo, Quintiles, Eli Lilly, Parexel, Astellas, Astellas Amgen Biopharma, Asahi Kasei Pharma, Eisai, Bayer; Financial Interests, Institutional, Funding: Chugai, Nippon Kayaku. Y. Komatsu: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd., Daiichi Sankyo, Taiho, Chugai, Lilly, Merck, MSD, BMS; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical Co. Ltd., Taiho, Chugai, Sanofi, Nipro, Daiichi Sankyo, BMS; Non-Financial Interests, Member: JSCO, JSMO, ASCO. S. Hironaka: Financial Interests, Personal, Other, lecture: Ono Pharm, BMS, Eli Lilly, Taiho, Daiichi Sankyo, MSD, Chugai, Merck Biopharma, Takeda, Yakult Honsha. All other authors have declared no conflicts of interest.