LBA6_PR - Nivolumab (nivo) plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC)/esophageal adenocarcinoma (EAC): First results of the CheckMate 649 study

Background

Standard 1L chemo options for advanced or metastatic HER2-negative GC/GEJC result in poor overall survival (OS; median < 1 year). CheckMate 649 is the largest randomized, global phase III study of programmed death (PD)-1 inhibitor-based therapies in 1L GC/GEJC/EAC. We report OS at a pre-specified interim analysis and progression-free survival (PFS) at final analysis from the NIVO + chemo vs chemo arms in patients (pts) whose tumors expressed PD-ligand 1 (L1) combined positive score (CPS) ≥ 5.

Methods

Adults with previously untreated, unresectable advanced, or metastatic GC/GEJC/EAC were enrolled, regardless of PD-L1 expression. Pts with known HER2-positive status were excluded. Pts were randomized to receive 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, in pts whose tumors expressed PD-L1 CPS ≥ 5.

Results

1581 pts were concurrently randomized in nivo+chemo and chemo arms, including 955 pts (60%) with PD-L1 CPS ≥ 5. With a minimum follow-up of 12 months (mo), NIVO + chemo showed a statistically significant improvement in OS and PFS vs chemo in pts whose tumors expressed PD-L1 CPS ≥ 5 (OS, HR 0.71 [98.4% CI 0.59–0.86; P < 0.0001] and PFS, HR 0.68 [98% CI 0.56–0.81; P < 0.0001]). Statistically significant OS benefit was also observed in pts with PD-L1 CPS ≥ 1 and the all-randomized population (Table). No new safety signals were identified. Safety results are described in the table. Table: LBA6_PR

Conclusions

NIVO is the first PD-1 inhibitor to demonstrate superior OS and PFS in combination with chemo vs chemo alone in previously untreated pts with advanced GC/GEJC/EAC, with a manageable safety profile. NIVO + chemo represents a potential new standard 1L treatment option for these pts.

Clinical trial identification

NCT02872116.

Editorial acknowledgement

Writing and editorial assistance was provided by Tanmayi Mankame, PhD, of Parexel International, funded by Bristol-Myers Squibb Company.

Legal entity responsible for the study

Bristol-Myers Squibb Company.

Funding

Bristol-Myers Squibb Company.

Disclosure

M. Moehler: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Adboards: Bristol Myers Squibb. K. Shitara: Advisory/Consultancy, Research grant/Funding (institution): Astellas Pharma; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly and Company; Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy: Takeda Pharmaceuticals; Advisory/Consultancy: Pfizer Inc; Advisory/Consultancy: Ono Pharmaceutical; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: AbbVie Inc; Honoraria (self): Yakult; Research grant/Funding (institution): Dainippon Sumitomo Pharma; Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Chugai Pharma; Advisory/Consultancy, Research grant/Funding (institution): Merck Pharmaceutical; Research grant/Funding (institution): Medi Science; Advisory/Consultancy: GlaxoSmithKline. M. Garrido: Advisory/Consultancy, Research grant/Funding (institution): Bristol Myers Squibb; Advisory/Consultancy: MSD; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Roche. K. Yamaguchi: Advisory/Consultancy, Research grant/Funding (institution): Taiho; Advisory/Consultancy: Chugai; Research grant/Funding (institution): Sanofi; Advisory/Consultancy, Research grant/Funding (institution): Daiichi-Sankyo; Advisory/Consultancy: Lilly; Advisory/Consultancy, Research grant/Funding (institution): Ono; Advisory/Consultancy, Research grant/Funding (institution): Yakult Honsha; Advisory/Consultancy: Takeda; Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy: Merck Serono. M. Schenker: Research grant/Funding (self), fee for clinical research activity: Bristol Myers Squibb; Research grant/Funding (self), fee for clinical research activity: Roche; Research grant/Funding (self), fee for clinical research activity: Pfizer; Research grant/Funding (self), fee for clinical research activity: MSD; Research grant/Funding (self), fee for clinical research activity: Eli Lilly; Research grant/Funding (self), fee for clinical research activity: Novartis; Research grant/Funding (self), fee for clinical research activity: Astellas; Research grant/Funding (self), fee for clinical research activity: GSK; Research grant/Funding (self), fee for clinical research activity: AstraZeneca; Research grant/Funding (self), fee for clinical research activity: Merck Serono; Research grant/Funding (self), fee for clinical research activity: Regeneron. M. Tehfe: Advisory/Consultancy: Bristol Myers Squibb. V. Poulart: Full/Part-time employment: Bristol Myers Squibb. D. Cullen: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol Myers Squibb. M. Lei: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol Myers Squibb. K. Kondo: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol Myers Squibb. M. Li: Full/Part-time employment: Bristol Myers Squibb. J.A. Ajani: Advisory/Consultancy, Research grant/Funding (institution): Bristol Myers Squibb. Y.Y. Janjigian: Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Speaker Bureau/Expert testimony: ASCO; Advisory/Consultancy: Michael J. Hennessy Associates; Advisory/Consultancy: Paradigm Medical Communications, LLC; Advisory/Consultancy: Zymeworks Inc.; Advisory/Consultancy: Jounce Therapeutics; Advisory/Consultancy: Seattle Genetics; Shareholder/Stockholder/Stock options: Rgenix; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Daiichi Sankyo; Research grant/Funding (institution): Ono Pharma; Advisory/Consultancy, Research grant/Funding (institution): Merck & Co Inc.; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Imugene. All other authors have declared no conflicts of interest.