Circulating tumor DNA, pathological and immunologic responses to neoadjuvant nivolumab or nivolumab plus relatlimab and chemoradiotherapy in resectable esophageal/gastroesophageal junction cancer

Gastroesophageal tumor kinetics during immune checkpoint inhibition (ICI) remain poorly understood. We report a phase II trial that evaluated neoadjuvant nivolumab (arm A) or nivolumab-relatlimab (arm B) in combination with chemoradiotherapy in 32 patients with resectable gastroesophageal cancer together with an in-depth evaluation of pathological, molecular and functional immune responses (NCT03044613). Patients with undetectable circulating tumor DNA (ctDNA) post-ICI induction, pre- and post-operatively had a significantly longer RFS and OS. Cell-free tumor load contraction was reflective of neoantigen-specific T-cell responses. Our findings highlight tumor kinetics during ICI that may open a therapeutic window for future intervention.EGA study EGAS00001007299