Multicenter phase 1b trial of neoadjuvant nivolumab or nivolumab plus relatlimab in resectable esophageal/gastroesophageal junction cancer

Over the past few decades, there have been limited therapeutic advances in the clinical management of resectable gastroesophageal cancers. A multicenter phase 1b trial in the United States evaluated neoadjuvant anti-PD-1 nivolumab (arm A) or neoadjuvant nivolumab plus anti-LAG-3 relatlimab in combination with chemoradiotherapy in patients with resectable stage II or III esophageal/gastroesophageal junction (E/GEJ) cancer. The study met the primary endpoint of safety in arm A; arm B required modification to mitigate toxicity. Pathological complete response and major pathological rates rates were 40% and 53.3% for arm A and 21.4% and 57.1% for arm B. Most common adverse events were fatigue, nausea, thrombocytopenia, and dermatitis. Overall, 2-year recurrence-free and overall survival rates were 72.5% and 82.6%, respectively. Patients with undetectable circulating tumor DNA at baseline, preoperatively, and postoperatively had longer RFS and OS. The authors conclude that the study provide insight into the safety profile of combined PD-1 and LAG-3 blockade in E/GEJ cancer, and highlight the potential of ctDNA analysis to dynamically assess systemic tumor burden during neoadjuvant ICI therapy.