LBA7 - Nivolumab (NIVO) plus chemotherapy (Chemo) or ipilimumab (IPI) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): CheckMate 649 study

Background

CheckMate 649, a randomized, global phase 3 study of 1L programmed death (PD) 1 inhibitor-based therapies in advanced GC/GEJC/EAC, demonstrated superior overall survival (OS) with NIVO + chemo vs chemo, leading to US FDA approval. We report longer-term follow-up for NIVO + chemo vs chemo and first results for NIVO + IPI vs chemo.

Methods

Adults with previously untreated, unresectable advanced or metastatic GC/GEJC/EAC were enrolled regardless of PD-ligand 1 (PD-L1) expression. Patients (pts) with known HER2-positive status were excluded. Pts were randomized to NIVO (360 mg Q3W or 240 mg Q2W) + chemo (XELOX Q3W or FOLFOX Q2W), NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses, then NIVO 240 mg Q2W), or chemo. Dual primary endpoints were OS and progression-free survival (PFS; per blinded independent central review [BICR]) for NIVO + chemo vs chemo in pts with PD-L1 combined positive score (CPS) ≥ 5. Hierarchically tested secondary endpoints included OS in NIVO + chemo vs chemo (PD-L1 CPS ≥ 1, then all randomized) and OS in NIVO + IPI vs chemo (PD-L1 CPS ≥ 5, then all randomized).

Results

Of 2031 pts, 1581 (60% with PD-L1 CPS ≥ 5) were concurrently randomized to NIVO + chemo or chemo and 813 (58% with PD-L1 CPS ≥ 5) to NIVO + IPI or chemo. NIVO + chemo continued to show improvement in OS vs chemo alone with an additional 12-mo follow-up from the primary analysis (Table). The secondary endpoint of OS in pts with PD-L1 CPS ≥ 5 for NIVO + IPI vs chemo group was not met (minimum follow-up, 35.7 mo; Table); other endpoints in the hierarchy were not tested. No new safety signals were identified. Additional results are shown in the table.

Conclusions

NIVO + chemo continued to demonstrate clinically meaningful long-term survival benefit vs chemo and an acceptable safety profile with additional follow-up, further supporting its use as a new standard 1L treatment in pts with advanced GC/GEJC/EAC. Table: LBA7

^aPer BICR m, median; ORR, objective response rate; TRAE, treatment-related adverse event

Clinical trial identification

NCT02872116.

Editorial acknowledgement

Writing and editorial assistance was provided by Puneet Dang, PhD of Parexel International, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

Y.Y. Janjigian: Financial Interests, Personal, Other, Consulting fees: Bristol Myers Squibb; Financial Interests, Personal, Other, Consulting fees: Merck Serono; Financial Interests, Personal, Other, Consulting fees: RGENIX; Financial Interests, Personal, Other, Consulting fees: Eli Lilly; Financial Interests, Personal, Other, Consulting fees: Daiichi Sankyo; Financial Interests, Personal, Other, Consulting fees: Pfizer; Financial Interests, Personal, Other, Consulting fees: Bayer; Financial Interests, Personal, Other, Consulting fees: Imugene; Financial Interests, Personal, Other, Consulting fees: Merck; Financial Interests, Personal, Other, Consulting fees: Zymeworks; Financial Interests, Personal, Other, Consulting fees: Seattle Genetics; Financial Interests, Personal, Other, Consulting fees: Basilea Pharmaceutica; Financial Interests, Personal, Other, Consulting fees: AstraZeneca; Financial Interests, Personal, Stocks/Shares: RGENIX; Financial Interests, Personal, Research Grant: NCI, Department of Defense, Cycle for Survival, Fred’s Team; Financial Interests, Personal, Research Grant: RGENIX; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: Genentech/Roche; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Eli Lilly; Financial Interests, Personal, Research Grant: Merck. J.A. Ajani: Financial Interests, Personal, Other, Consulting or Advisory Role: American Cancer Society; Financial Interests, Personal, Other, Consulting or Advisory Role: BeiGene; Financial Interests, Personal, Other, Consulting or Advisory Role: Vaccinogen; Financial Interests, Personal, Other, Consulting or Advisory Role: Insys Therapeutics; Financial Interests, Personal, Other, Consulting or Advisory Role: Merck; Financial Interests, Personal, Other, Consulting or Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Genentech; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Taiho; Financial Interests, Personal, Research Grant: MedImmune; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Research Grant: Amgen; Financial Interests, Personal, Research Grant: Lilly; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Aduro Biotech; Financial Interests, Personal, Other, Honoraria: DAVA Pharmaceuticals; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Acrotech Biopharma; Financial Interests, Personal, Other, Honoraria: Zymeworks; Financial Interests, Personal, Other, Honoraria: Astellas Pharma; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Taiho Pharmaceutical; Financial Interests, Personal, Research Grant: Roche/Genentech; Financial Interests, Personal, Research Grant: Amgen; Financial Interests, Personal, Research Grant: Lilly/ImClone; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Research Grant: Delta-Fly Pharma; Financial Interests, Personal, Research Grant: Gilead Sciences; Financial Interests, Personal, Research Grant: Takeda; Financial Interests, Personal, Research Grant: ProLynx; Financial Interests, Personal, Research Grant: Zymeworks; Financial Interests, Personal, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Astellas Pharma. M. Moehler: Financial Interests, Personal, Other, Consulting or Advisory Role: Bayer; Financial Interests, Personal, Other, Consulting or Advisory Role: MSD; Financial Interests, Personal, Other, Consulting or Advisory Role: Merck Serono; Financial Interests, Personal, Other, Consulting or Advisory Role: Amgen; Financial Interests, Personal, Other, Consulting or Advisory Role: Taiho Pharmaceutical; Financial Interests, Personal, Other, Consulting or Advisory Role: Pfizer; Financial Interests, Personal, Other, Consulting or Advisory Role: Roche; Financial Interests, Personal, Other, Consulting or Advisory Role: Lilly; Financial Interests, Personal, Other, Consulting or Advisory Role: Servier; Financial Interests, Personal, Other, Consulting or Advisory Role: BeiGene; Financial Interests, Personal, Other, Consulting or Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Amgen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck Serono; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bayer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: ASCO; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: German Cancer Society; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: ESMO; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Roche/Genentech; Financial Interests, Personal, Other, Honoraria: Merck Serono; Financial Interests, Personal, Other, Honoraria: MSD Oncology; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: AstraZeneca/MedImmune; Financial Interests, Personal, Other, Honoraria: Servier; Financial Interests, Personal, Other, Honoraria: Pierre Fabre; Financial Interests, Personal, Other, Honoraria: Sanofi; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Leap Therapeutics; Financial Interests, Institutional, Research Grant: Merck Serono; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: MSD. M. Garrido: Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Other, Consulting Fee: Roche; Financial Interests, Personal, Expert Testimony: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD; Financial Interests, Personal, Advisory Board: Roche. C. Gallardo: Financial Interests, Personal, Other, Consulting Fee: Roche; Financial Interests, Personal, Other, Consulting Fee: AstraZeneca; Financial Interests, Personal, Other, Consulting Fee: MSD; Financial Interests, Personal, Other, Consulting Fee: Novartis; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Expert Testimony: Novartis; Financial Interests, Personal, Expert Testimony: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis. L. Shen: Financial Interests, Institutional, Research Grant: Beijing Xiantong Biomedical Technology; Financial Interests, Institutional, Research Grant: Qilu Pharmaceutical; Financial Interests, Institutional, Research Grant: ZaiLab Pharmaceutical (Shanghai); Financial Interests, Institutional, Research Grant: Beihai Kangcheng(Beijing)Medical Technology; Financial Interests, Institutional, Research Grant: Jacobio Pharmaceuticals; Financial Interests, Institutional, Research Grant: Beijing Xiantong; Financial Interests, Institutional, Research Grant: Biomedical Technology; Financial Interests, Personal, Other, Consulting fee: MSD; Financial Interests, Personal, Other, Consulting fee: Merk; Financial Interests, Personal, Other, Consulting fee: Mingji biopharmaceutical; Financial Interests, Personal, Other, Consulting fee: Haichuang pharmaceutical; Financial Interests, Personal, Other, Consulting fee: Herbour biomed; Financial Interests, Personal, Other, Consulting fee: BI; Financial Interests, Personal, Speaker’s Bureau: Hutchison Whampoa; Financial Interests, Personal, Speaker’s Bureau: Hengrui; Financial Interests, Personal, Speaker’s Bureau: ZaiLab; Financial Interests, Personal, Speaker’s Bureau: CSTONE pharmaceutical; Financial Interests, Personal, Advisory Board: Rongchang pharmaceutical; Financial Interests, Personal, Advisory Board: ZaiLab; Financial Interests, Personal, Advisory Board: CSTONE pharmaceutical; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb. K. Yamaguchi: Financial Interests, Personal, Other, Consulting or Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Other, Consulting or Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharma; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb Japan; Financial Interests, Personal, Speaker’s Bureau: Takeda; Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Gilead Sciences; Financial Interests, Institutional, Research Grant: Yakult Honsha; Financial Interests, Institutional, Research Grant: Chugai Pharma; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: MSD Oncology; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb. L. Wyrwicz: Financial Interests, Personal, Other, Consulting or Advisory Role: Amgen; Financial Interests, Personal, Other, Consulting or Advisory Role: Servier; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: Sanofi Aventis; Financial Interests, Personal, Speaker’s Bureau: Servier; Financial Interests, Personal, Other, Patents, Royalties, Other Intellectual Property: National Cancer Research Institute. M. Tehfe: Financial Interests, Personal, Other, Consultancy or Advisory: Celgene; Financial Interests, Personal, Other, Consultancy or Advisory: Merck; Financial Interests, Personal, Other, Consultancy or Advisory: Taiho Pharmaceutical; Financial Interests, Personal, Other, Consultancy or Advisory: AstraZeneca; Financial Interests, Personal, Other, Consultancy or Advisory: Takeda; Financial Interests, Personal, Other, Consultancy or Advisory: Bayer; Financial Interests, Personal, Other, Consultancy or Advisory: Bristol Myers Squib; Financial Interests, Personal, Other, Consultancy or Advisory: Eisai; Financial Interests, Personal, Speaker’s Bureau: Celgene; Financial Interests, Personal, Other, Honoraria: Celgene; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Research Grant: Celgene. E. Elimova: Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Zymeworks; Financial Interests, Institutional, Other, Consulting fees: Adaptimmune; Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Board: Zymeworks; Financial Interests, Personal, Other, Spouse employee: Merck Vaccines. M. Li: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, accommodations, expenses: Bristol Myers Squibb. V. Poulart: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. M. Lei: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Personal, Other, Patent, Royalties, Other intellectual property: Bristol Myers Squibb. K. Kondo: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Other, Travel, accommodations, expenses: Bristol Myers Squibb. K. Shitara: Financial Interests, Personal, Advisory Board: Eli Lilly and Company; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Takeda Pharmaceuticals; Financial Interests, Personal, Advisory Board: Pfizer Inc; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical; Financial Interests, Personal, Research Grant: Ono Pharmaceutical; Financial Interests, Personal, Other, Honoraria (lecture fee): Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Astellas Pharma; Financial Interests, Personal, Research Grant: Astellas Pharma; Financial Interests, Personal, Research Grant: Eli Lilly and Company; Financial Interests, Personal, Other, Honoraria (lecture fee): AbbVie Inc; Financial Interests, Personal, Advisory Board: AbbVie Inc; Financial Interests, Personal, Other, Honoraria (lecture fee): Yakult; Financial Interests, Personal, Research Grant: Dainippon Sumitomo Pharma; Financial Interests, Personal, Research Grant: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Taiho Pharmaceutical; Financial Interests, Personal, Research Grant: Taiho Pharmaceutical; Financial Interests, Personal, Research Grant: Chugai Pharma; Financial Interests, Personal, Advisory Board: Merck Pharmaceutical; Financial Interests, Personal, Research Grant: Merck Pharmaceutical; Financial Interests, Personal, Research Grant: Medi Science; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Research Grant: Eisai. All other authors have declared no conflicts of interest.