Abstract 398P
Background
NIVO + chemo and NIVO + IPI are approved for the treatment of advanced ESCC in the US, EU, Japan, and many other countries based on the results from CheckMate 648 (NCT03143153). Here, we report 45-mo follow-up results.
Methods
Adults with previously untreated, unresectable advanced, recurrent, or metastatic ESCC were randomized to NIVO (240 mg Q2W) + chemo (fluorouracil + cisplatin Q4W), NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W) or chemo. The primary endpoints were overall survival (OS) and progression-free survival (PFS) per blinded independent central review (BICR) in patients (pts) with tumor cell programmed death ligand 1 (PD-L1) ≥ 1%.
Results
In total, 970 pts were randomized to NIVO + chemo, NIVO + IPI, or chemo; 473 pts had tumor cell PD-L1 ≥ 1%. With 45-mo minimum follow-up, NIVO + chemo and NIVO + IPI demonstrated continued OS benefit and higher 45-mo OS rates vs chemo in pts with tumor cell PD-L1 ≥ 1% (Table). Duration of response (DOR) was longer (Table) and the proportion of responders with DOR ≥ 45 mo was greater with NIVO + chemo and NIVO + IPI vs chemo in pts with tumor cell PD-L1 ≥ 1% (7% and 23% vs 0%, respectively). Additional analyses will be presented. Among all treated pts, any-grade treatment-related adverse events (TRAEs) occurred in 96% of pts with NIVO + chemo, 80% with NIVO + IPI, and 90% with chemo; grade 3/4 TRAEs occurred in 49%, 33%, and 37% of pts, respectively. No additional TRAEs leading to discontinuation and no new treatment-related deaths were reported with longer follow-up. Table: 398P
| Efficacy | Tumor cell PD-L1 ≥ 1% | ||
| NIVO + chemo (n = 158) | NIVO + IPI (n = 158) | Chemo (n = 157) | |
| mOS (95% CI), mo | 15.0 (11.9–18.7) | 13.1 (11.2–17.4) | 9.1 (7.7–10.0) |
| HR vs chemo (95% CI) | 0.60 (0.47–0.77) | 0.63 (0.49–0.81) | – |
| 45-mo OS rate (95% CI), % | 16 (11–23) | 19 (13–25) | 8 (5–14) |
| mPFS a (95% CI), mo | 6.8 (5.7–8.3) | 4.0 (2.3–4.4) | 4.4 (2.9–5.8) |
| HR vs chemo (95% CI) | 0.67 (0.51–0.88) | 1.03 (0.78–1.35) | – |
| 45-mo PFS rate (95% CI), % | 5 (2–11) | 9 (5–16) | 0 |
| ORR, a n (%) | 83 (53) | 55 (35) | 31 (20) |
| mDOR a , b (95% CI), mo | 8.4 (6.9–12.4) | 11.8 (6.8–18.0) | 5.7 (4.4–8.7) |
aPer BICR;
bEvaluated in responders. ORR, objective response rate.
Conclusions
After 45 mo of follow-up, NIVO + chemo and NIVO + IPI continued to demonstrate clinically meaningful survival benefit and more durable responses vs chemo, with no new safety signals. These results further support NIVO + chemo and NIVO + IPI as 1L treatment options for advanced ESCC.
Clinical trial identification
NCT03143153.
Editorial acknowledgement
Writing and editorial assistance were provided by Niesh Sule, PhD, of Parexel, funded by Bristol Myers Squibb.
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
A. Adenis: Financial Interests, Personal, Advisory Board: Arcus Biosciences, Astellas Pharma, Bayer Health, Bristol Myers Squibb; Merck; Merck Serono; Financial Interests, Personal, Speaker’s Bureau: MSD Oncology, Bristol Myers Squibb, Novartis; Financial Interests, Personal, Invited Speaker, Research Funding: Arcus Ventures (Inst), Bayer (Inst), BeiGene (Inst), Bristol Myers Squibb (Inst), Merck (Inst), Roche (Inst), Sanofi (Inst); Financial Interests, Personal, Invited Speaker, Travel, Accommodations, Expenses: Bristol Myers Squibb, Servier, MSD, Pierre Fabre. I. Chau: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Eli Lilly, MSD, Roche, Merck Serono, AstraZeneca, OncXerna, Boehringer Ingelheim, Astella, Incyte, GSK, Sotio, Daiichi Sankyo, Eisai, Taiho, Seagen, Turning Point Therapeutics, Novartis; Financial Interests, Personal, Invited Speaker: Eisai, Eli Lilly, Servier, Servier; Financial Interests, Institutional, Invited Speaker: Cilag-Janssen, Eli Lilly. J.A. Ajani: Financial Interests, Personal, Invited Speaker, 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, Zymeworks; Financial Interests, Personal, Advisory Role: American Cancer Society; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Advisory Board: Arcus Biosciences, Astellas Pharma, BeiGene, Bristol Myers Squibb, Geneos, Gilead Sciences, Insys Therapeutics, Merck, Novartis, Servier; Vaccinogen; Financial Interests, Funding, Research funding: Zymeworks, Takeda, Taiho Pharmaceutical, Roche/Genentech, ProLynx, Novartis, Merck, Lilly/ImClone, Gilead Sciences, Delta-Fly Pharma, Daiichi Sankyo, Bristol Myers Squibb, Astellas Pharma (Inst), Amgen; Financial Interests, Royalties: Genentech, Roche, BMS, Taiho, MedImmune, Merck, Amgen, Lilly. Y. Kitagawa: Financial Interests, Personal, Other, Honoraria: Asahi Kasei, ASKA Pharmaceutical Co., Ltd., AstraZeneca Japan, Bristol Myers Squibb K.K., Chugai Foundation for Innovative Drug Discovery Science, Chugai Pharma, Daiichi Sankyo Company, Limited, EA Pharma, Ethicon, Intuitive Surgical, Kaken Pharmaceutical, Miyarisan Pharmaceutical, MSD K.K., Nippon Covidien, Nippon Kayaku, Olympus, Ono Pharmaceutical, Otsuka, Shionogi, Smith & Nephew, Sysmex, Taiho Pharmaceutical, Toray Industries; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb K.K., Ono Pharmaceutical; Financial Interests, Personal, Funding, Research funding: Asahi Kasei (Inst), Chugai Pharma (Inst), Eisai (Inst), Kaken Pharmaceutical (Inst), Kowa (Inst), Kyouwa Hakkou Kirin Co., Ltd. (Inst), Nippon Covidien (Inst), Otsuka (Inst), Sumitomo Pharma Co., Ltd. (Inst), Taiho Pharmaceutical (Inst), Takeda (Inst), Teijin Pharma (Inst), Tsumura & Co. (Inst). L.S. Wyrwicz: Financial Interests, Personal, Other, Honoraria: MSD, BMS, BeiGene; Financial Interests, Personal, Advisory Board: GSK, Servier; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Servier. T. Ogata: Financial Interests, Personal, Invited Speaker, Speakers' Bureau: Bristol Myers Squibb Foundation, Ono Pharmaceutical, MSD. 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 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, 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. C. Hsu: Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Eisai; Merck Sharp & Dohme; Ono Pharmaceutical; Roche, Eisai, Merck Sharp & Dohme, Ono Pharmaceutical, Roche; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck Serono, MSD, Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker, Research Funding: AstraZeneca (Inst), BeiGene (Inst), Bristol Myers Squibb (Inst), Eucure Biopharma (Inst), Johnson & Johnson (Inst), Merck Serono (Inst), MSD (Inst), NGM Biopharmaceuticals (Inst); Nucana (Inst); Ono Pharmaceutical (Inst); Roche/Genentech (Inst); Taiho Pharmaceutical (Inst), Nucana (Inst), Ono Pharmaceutical (Inst), Roche/Genentech (Inst), Taiho Pharmaceutical (Inst). M. Di Bartolomeo: Financial Interests, Personal, Other, Honoraria: BMS, Lilly, MSD Oncology, Servier; Financial Interests, Personal, Advisory Board: MSD Oncology, Lilly; Financial Interests, Personal, Funding, Research Funding: Lilly (Inst); Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Daiichi Sankyo, AstraZeneca. M.I. Braghiroli: Financial Interests, Personal, Other, Honoraria: Amgen, BMS Brazil, Eurofarma, MSD, Takeda; Financial Interests, Personal, Advisory Board: Servier, Roche, MSD, Merck, Lilly; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD. M. Blum Murphy: Financial Interests, Personal, Funding, Research Funding: Bristol Myers Squibb (Inst), Genentech/Roche (Inst). J. Zhang: Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. N. Hu: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. Y. Matsumura: Financial Interests, Personal, Full or part-time Employment: Ono Pharmaceutical; Financial Interests, Personal, Stocks/Shares: Ono Pharmaceutical. K. Kato: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, Bristol Myers Squibb, Merck and Co; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical, Bristol Myers Squibb, Merck and Co, Bayer, AstraZeneca, BeiGene, Taiho, Merck Biopharma, Amgen, Novartis; Financial Interests, Personal, Expert Testimony: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Ono Pharmaceuticals, Merck & Co, Bayer, AstraZeneca, BeiGene, Chugai, Taiho, Oncolys Biopharma, Janssen Pharmaceutical. Y. Doki: Financial Interests, Personal, Other, Honoraria: Chugai Pharma, Daiichi Sankyo, Lilly Japan, MSD, Ono Pharmaceutical, Otsuka, Taiho Pharmaceutical; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical; Financial Interests, Personal, Funding, Research Funding: Chugai Pharma, Daiichi Sankyo, Ono Pharmaceutical, Taiho Pharmaceutical, Yakult Honsha. All other authors have declared no conflicts of interest.