Phase Ib/II Trial of Durvalumab and Chemoradiation (CRT) with Carboplatin/paclitaxel for Esophageal and Gastroesophageal Junction (GEJ) Adenocarcinoma.

172 Background: Pre-op CRT with carboplatin (C)/paclitaxel (P) and radiation (RT) for locally advanced esophageal cancer is a standard of care, based on the CROSS trial (NEJM 2012;366:2074). However, outcomes remain poor. Early data suggest activity of durvalumab (D) in GEJ/gastric cancer [Ann Oncol 25:iv361-372; 2014]. In a pilot study, we assessed safety of D + C/P + RT as pre-op therapy. Methods: Patients (Pts) had TanyN+ or T3-4NanyM0 esophageal and Siewert Type I/II GEJ adenocarcinoma staged by EUS, PET/CT and CT. Pts received D 1500mg x 1 dose and 4 weeks later C AUC2 and P 50mg/m2 weekly x 5 with RT (1.8Gy daily fractions to 50.4Gy). Pts also received D 1,500mg at first dose of C/P and RT. PET/CT was repeated 21-27 days post D and 4-6 weeks post CRT. Esophagectomy was planned 6-8 weeks after CRT. Pts who had R0 resections received adjuvant D 1,500mg 4 weekly x 6 doses. Initially, 6 patients were treated and followed for 30 days after surgery to assess for unacceptable toxicities. Results: 6 pts were enrolled: 3 Siewert I (50%), 2 Siewert II (33%), 1 esophageal (17%); 5 T3N1-2, 1 T4aN1. 5 pts (83%) underwent sx. 1 pt was retrospectively assessed to have metastases after induction D and taken off-study. Pathologic response was 60% in 2 pts, 90% in 1 pt, 80% in 1 pt and 40% in 1 pt; no complete response was seen. Significant grade 3/4 toxicity observed during D and CRT was neutropenia in 1 pt (17%). Adverse events (AEs) of any grade in ≥20%: lymphopenia (5 pts), thrombocytopenia (5 pts), leucopenia (4 pts), fatigue (3 pts), anemia (3 pts), neutropenia (3 pts) and abdominal pain (2 pts). Immune-related AEs were hypothyroidism (grade 2; 1 pt) and nephritis (grade 2; 1 pt). Surgical complications: 2 esophageal strictures, 1 pneumonia and 1 anastomotic leak with airway fistula, successfully treated with a stent. Immune correlative analyses from tumor blocks and whole blood are ongoing and will be reported in the poster. Conclusions: The addition of D to pre-op CRT in esophageal and GEJ adenocarcinoma appears feasible and safe. We observed no unacceptable toxicity. The study is being modified to incorporate use of induction chemo and PET (based on CALGB 80803 results) and expanded to a multicenter setting. Clinical trial information: NCT02962063.