837TiPPRODIGE67_UCGI33 ARION: Association of radiochemotherapy and immunotherapy for the treatment of unresectable oesophageal cancer: A comparative randomized phase II trial

Abstract Background Overall survival (OS) of locally advanced esophageal cancer remains poor with a 5-year survival of 15-34%. The standard treatment is definitive radiotherapy delivered with oxaliplatin-based chemotherapy (RCT). Majority of patients (pts) die due to non-complete response, local recurrence and/or metastatic progression and the efficacy of definitive RCT need to be increased. The immune checkpoint inhibitors, anti-programmed death 1 (PD-1) and anti-programmed death ligand 1 (PD-L1), demonstrated promising antitumor activity and manageable safety profile when used as monotherapy in metastatic esophageal squamous cell carcinoma. PD-L1 expression increased in esophageal cancer pts after neoadjuvant RCT but still associated with poor OS. The immune tumor microenvironment for tumor response has raised novel hypotheses regarding newer immunomodulatory approaches during radiotherapy, especially abscopal effect to improve local and distant outcome. Durvalumab (MEDI4736) is a selective high affinity human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80. We hypothesize that combining durvalumab with RCT can increase local response to treatment and prevent distant metastases. Trial design This multicentric, open-label, comparative phase II trial plans to randomize (1:1) 120 pts (≥18 years old, WHO