This phase Ib trial evaluated neoadjuvant nivolumab (Arm A, n=16) or nivolumab-relatlimab (Arm B, n=16) with chemoradiotherapy in 32 patients with resectable stage II/III gastroesophageal cancer. The primary endpoint was safety; secondary, feasibility; exploratory endpoints included pathological complete response (PCR), major pathological response (MPR), recurrence-free survival (RFS), and overall survival (OS). Arm B required modification due to toxicity. PCR and MPR rates were 40% and 53.5% (Arm A) and 21.4% and 57.1% (Arm B). Two-year RFS and OS rates were 72.5% and 82.6%, respectively. Higher baseline PD-L1 and LAG-3 expression correlated with better responses. ctDNA analysis showed that patients with undetectable ctDNA post-ICI induction had significantly longer RFS and OS, reflecting neoantigen-specific T cell responses.

Ronan J. Kelly, Blair V. Landon, Ali H. Zaidi, Dipika Singh, Jenna V. Canzoniero, Archana Balan, Russell K. Hales, K. Ranh Voong, Richard J. Battafarano, Blair A. Jobe, Stephen C. Yang, Stephen Broderick, Jinny Ha, Kristen A. Marrone, Gavin Pereira, Nisha Rao, Aryan Borole, Katerina Karaindrou, Zineb Belcaid, James R. White, Suqi Ke, Ali I. Amjad, Benny Weksler, Eun Ji Shin, Elizabeth Thompson, Kellie N. Smith, Drew M. Pardoll, Chen Hu, Josephine L. Feliciano, Valsamo Anagnostou, Vincent K. Lam