Nivolumab plus chemotherapy or ipilimumab in gastroesophageal cancer: CheckMate 649 biomarker analyses

First-line nivolumab-plus-chemotherapy demonstrated superior overall survival (OS) versus chemotherapy for advanced gastroesophageal adenocarcinoma (CheckMate 649). Nivolumab-plus-ipilimumab provided durable responses and higher survival rates versus chemotherapy; however, the prespecified OS significance boundary was not met. To identify biomarkers predictive of differential efficacy outcomes, exploratory analyses were performed using whole-exome sequencing and RNA sequencing. Nivolumab-based therapies demonstrated improved efficacy versus chemotherapy in hypermutated and, to a lesser degree, Epstein Bar Virus-positive tumors compared with chromosomally unstable and genomically stable tumors. Within the KRAS-altered subgroup, only patients treated with nivolumab-plus-chemotherapy demonstrated improved OS benefit versus chemotherapy. Low stroma gene expression signature scores were associated with OS benefit with nivolumab-based regimens; high regulatory T-cell signatures were associated with OS benefit only with nivolumab-plus-ipilimumab. Our analyses suggest that distinct and overlapping pathways contribute to the efficacy of nivolumab-based regimens in gastroesophageal adenocarcinoma.

Type: Cancer Genomics
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD50000001105	This dataset contains RNA sequencing (RNAseq) data of 814 patients from the CheckMate 649 clinical trial whose ICF allows data deposition into a public repository. Gene expression profiling was performed retrospectively using RNAseq on a subset of baseline tumor samples. Paired-end FASTQ files were processed on Seven Bridges platform (Seven Bridges Genomics).	Illumina NovaSeq 6000	814

Publications	Citations
Nivolumab plus chemotherapy or ipilimumab in gastroesophageal cancer: exploratory biomarker analyses of a randomized phase 3 trial. Shitara K, Janjigian YY, Ajani J, Moehler M, Yao J, Wang X, Chhibber A, Pandya D, Shen L, Garrido M, Gallardo C, Wyrwicz L, Yamaguchi K, Skoczylas T, Bragagnoli A, Liu T, Schenker M, Yañez P, Kowalyszyn R, Karamouzis M, Zander T, Feeney K, Elimova E, Doshi P, Li M, Lei M. Nat Med 31: 2025 1519-1530	6

Publications

Citations

Nivolumab plus chemotherapy or ipilimumab in gastroesophageal cancer: exploratory biomarker analyses of a randomized phase 3 trial.
Shitara K, Janjigian YY, Ajani J, Moehler M, Yao J, Wang X, Chhibber A, Pandya D, Shen L, Garrido M, Gallardo C, Wyrwicz L, Yamaguchi K, Skoczylas T, Bragagnoli A, Liu T, Schenker M, Yañez P, Kowalyszyn R, Karamouzis M, Zander T, Feeney K, Elimova E, Doshi P, Li M, Lei M. Nat Med 31: 2025 1519-1530