Abstract 419P
Background
NIVO + chemo demonstrated superior overall survival (OS) and clinically meaningful progression-free survival (PFS) benefit vs chemo and an acceptable safety profile in previously untreated, advanced non-HER2+ GC/GEJC/EAC, leading to approvals in many countries. NIVO + chemo continued to demonstrate clinically meaningful improvement in efficacy at 2 and 3-y FUs. We present 4-y FU results for NIVO + chemo vs chemo from CheckMate 649.
Methods
Adults with previously untreated, unresectable advanced, or metastatic GC/GEJC/EAC were enrolled, regardless of programmed death ligand 1 (PD-L1) expression. HER2+ patients (pts) were excluded. Randomized pts received NIVO (360 mg Q3W or 240 mg Q2W) + chemo (XELOX Q3W or FOLFOX Q2W), NIVO + ipilimumab, or chemo. Dual primary endpoints for NIVO + chemo vs chemo were OS and PFS by blinded independent central review (BICR) in pts with PD-L1 combined positive score (CPS) ≥ 5.
Results
1581 pts were randomized to NIVO + chemo or chemo; 955 had PD-L1 CPS ≥ 5. At the 48-month (mo) minimum FU, NIVO + chemo continued to demonstrate OS (including a doubling of survivors at 48-mos) and PFS benefit vs chemo in pts with PD-L1 CPS ≥ 5 (Table). OS benefit with NIVO + chemo was observed in most prespecified subgroups. Objective response rates (ORR) were higher and responses were more durable with NIVO + chemo vs chemo in pts with PD-L1 CPS ≥ 5 (Table). Additional analyses will be presented, including health-related quality of life results. No new safety signals were identified, consistent with the 3-y FU. Table: 419P
| Efficacy | PD-L1 CPS ≥ 5 | |
| NIVO + chemo (n = 473) | Chemo (n = 482) | |
| mOS (95% CI) mo | 14.4 (13.1–16.2) | 11.1 (10.1–12.1) |
| HR (95% CI) | 0.70 (0.61–0.81) | |
| 48-mo OS rate (95% CI) % | 17 (14–21) | 8 (6–11) |
| mPFS a (95% CI) mo | 8.3 (7.0–9.3) | 6.1 (5.6–6.9) |
| HR (95% CI) | 0.71 (0.61–0.82) | |
| ORR a , b (95% CI) % | 60 (55–65) | 45 (40–50) |
| mDuration of response a , c (95% CI) mo | 9.6 (8.3–12.4) | 7.0 (5.7–8.0) |
aPer BICR
bIn pts with measurable target lesions at baseline
cIn responders
Conclusions
NIVO + chemo is the first PD-1 inhibitor/chemo combination to demonstrate long-term efficacy and acceptable safety after 4 y of FU in previously untreated advanced GC/GEJC/EAC. These results are consistent with earlier FUs, further supporting NIVO + chemo as a standard 1L treatment in these pts.
Clinical trial identification
NCT02872116.
Editorial acknowledgement
Writing and editorial assistance were provided by Nitesh Sule, PhD, of Parexel, funded by Bristol Myers Squibb.
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
L.S. Wyrwicz: Financial Interests, Personal, Other, Honoraria: BeiGene, Bristol Myers Squibb, MSD; Financial Interests, Personal, Advisory Board: GSK, Servier; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Servier. K. Shitara: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Takeda, Ono Pharmaceutical, MSD, Novartis, Daiichi Sankyo, Amgen, Guardant Health Japan Corp, Astellas Pharma Inc., Astellas, Bayer, AstraZeneca, Zymeworks Biopharmaceuticals Inc, ALX Oncology Inc; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Janssen, AstraZeneca, Eli Lilly, Astellas, Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: Astellas, Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical, MSD, Eisai, Amgen, PRA Health Sciences. M. Moehler: Financial Interests, Personal, Advisory Board: BMS, Servier, Amgen, Lilly, BeiGene, Novartis, Taiho, Daiichi Sankyo, Amgen, MD; Financial Interests, Personal, Invited Speaker: MSD, BMS, Falk foundation, AIO, BeiGene, Amgen; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Expert Testimony: Sanofi; Financial Interests, Personal, Other, Chair: EORTC. J.A. Ajani: Financial Interests, Personal, Other, Honoraria: Acrotech Biopharma, Aduro Biotech, Amgen, Astellas Pharma, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Dava Pharmaceuticals, Fresenius Kabi, Gilead Sciences, Grail, Lilly, Merck, Novartis, Oncotherics, Servier; Financial Interests, Personal, Advisory Board: American Cancer Society, Amgen, Arcus Biosciences, Astellas Pharma, BeiGene, Bristol Myers Squibb, Geneos, Gilead Sciences, Insys Therapeutics, Merck, Novartis, Servier, Vaccinogen; Financial Interests, Personal, Funding, Research funding: Amgen, Astellas Pharma (Inst), Bristol Myers Squibb, Daiichi Sankyo, Delta-Fly Pharma, Gilead Sciences, Lilly/ImClone, Merck, Novartis, ProLynx, Roche/Genentech, Taiho Pharmaceutical, Takeda, Zymeworks; Financial Interests, Personal, Royalties, Patents, Royalties, Other Intellectual Property - I have research funding from: Genentech, Roche, BMS, Taiho, MedImmune, Merck, Amgen, Lilly: Genentech, Roche, Bristol Myers Squibb, Taiho Pharmaceutical, MedImmune, Merck, Amgen, Lilly. L. Shen: Financial Interests, Personal, Advisory Board: MSD, BI, Servier, AZ, Transcenta Holding Limited; Financial Interests, Institutional, Funding: BeiGene, Ltd.; Financial Interests, Institutional, Invited Speaker: Rongchang Pharmaceutical, Roche, Innovent, BeiGene, Ltd., NovaRock Biotherapeutics Limited. M. Garrido: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Roche; Financial Interests, Personal, Speaker’s Bureau: Bayer, Bristol Myers Squibb, Merck; Financial Interests, Personal, Funding, Research funding: Bristol Myers Squibb (Inst), Novartis (Inst); Financial Interests, Personal, Expert Testimony: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche. C.E. Gallardo Araneda: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Roche; Financial Interests, Personal, Speaker’s Bureau: Bayer, Bristol Myers Squibb, Merck KGaA; Financial Interests, Personal, Funding, Research funding: Bristol Myers Squibb, Novartis; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche. K. Yamaguchi: Financial Interests, Personal, Invited Speaker: Taiho Pharm; Financial Interests, Personal, Expert Testimony: Daiichi Sankyo, Bristol Mayers Squibb, Ono Pharm, Eli Lilly Japan; Financial Interests, Institutional, Funding: Taiho Pharm. J. Cleary: Financial Interests, Personal, Other, Honoraria: Blueprint Medicines, Incyte, Syros Pharmaceuticals; Financial Interests, Personal, Funding, Research Funding: Tesaro, Servier (Inst); Roche/Genentech (Inst), Merus (Inst), Merck, Esperas Pharma, BMS (Inst), Bayer, AstraZeneca, Arcus Biosciences, Apexigen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Agios, Bristol Myers Squibb, Incyte, Roche. E. Elimova: Financial Interests, Personal, Invited Speaker: Roche, Daiichi; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: BeiGene, Signatera, AbbVie, Astellas, Viracta Tx; Financial Interests, Institutional, Invited Speaker, Institution receives: Jazz; Financial Interests, Institutional, Invited Speaker: Jazz, Zymeworks, Amgen, AstraZeneca, BMS; Other, A family member employed by Merck Vaccines: Merck. R. Brugés Maya: Financial Interests, Personal, Advisory Board, Advisory board neoadjuvant therapy in breast cancer triple negative: MSD; Non-Financial Interests, Advisory Role, Advisory in triple negative breast cancer: MSD; Non-Financial Interests, Leadership Role, President of Asociacion Colombiana de Hematologia y Oncologia: ACHO. M.V. Karamouzis: Financial Interests, Personal, Invited Speaker: BMS, Servier, Ipsen, Astellas, Sanofi, AstraZeneca; Financial Interests, Personal, Advisory Board: MSD, Amgen, Specialty Therapeutics, Pierre Fabre. T. Skoczylas: Financial Interests, Personal, Funding, Research funding: Bristol Myers Squibb Japan; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Olympus. A.C. Bragagnoli: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb/Medarex, Merck. M. Tehfe: Financial Interests, Personal, Advisory Board: BMS, Merck, Pfizer, Taiho, Incyte; Financial Interests, Personal, Invited Speaker: BMS, Taiho; Financial Interests, Institutional, Invited Speaker: BMS, Amgen, Novartis, BioNTech; Financial Interests, Institutional, Research Grant: Pfizer, Taiho. R. Wang: Financial Interests, Full or part-time Employment: Bristol Myers Squibb. J. Zhang: Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. Y.Y. Janjigian: Financial Interests, Personal, Advisory Board: AbbVie, Arcus Biosciences, Ask- Gene Pharma, Inc., AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Inc., Eli Lilly, GSK, Guardant Health, Inc., Imugene, Lynx Health, Merck, Sanofi Genzyme, Seagen, Zymeworks Inc.; Financial Interests, Personal, Other, Consulting: Amerisource Bergen, Astellas, Basilea Pharmaceutica, Geneos Therapeutics, Imedex, Inspirna, Mersana Therapeutics, Paradigm Medical Communications, Pfizer, Silverback Therapeutics; Financial Interests, Personal, Other, Consulting and Invited Speaker: Arcus Biosciences, AstraZeneca, Clinical Care Options, HMP Education, Merck Serono, PeerView Institute, Research to Practice; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Ed MedResources (OncInfo), H.C. Wainwright & Co., LLC, Merck, TotalCME, AstraZeneca, Transcenta Holding Limited; Financial Interests, Personal, Other, Consulting, Invited Speaker and Chair of Giants of Cancer Care Steering Committee: Michael J. Hennessy Associates; Financial Interests, Personal, Other, Consulting and Moderator: Physicians' Education Resource, LLC; Financial Interests, Personal, Stocks/Shares, Stock option: Inspirna; Financial Interests, Personal and Institutional, Research Grant: NCI, Department of Defense, Cycle for Survival, Fred's Team, Inspirna, Bayer, Genentech/Roche, Bristol Myers Squibb, Eli Lilly, Merck, Transcenta, Stand Up To Cancer, AstraZeneca, Arcus Biosciences. All other authors have declared no conflicts of interest.