1204MO PRODIGE 59 - DURIGAST Trial: A Randomised Phase II Study Evaluating FOLFIRI Plus Durvalumab and FOLFIRI Plus Durvalumab Plus Tremelimumab in Second-Line Treatment of Patients with Advanced Gastric or Gastro-Oesophageal Junction Adenocarcinoma

No study up until now has evaluated the efficacy of immune checkpoint inhibitors combined with chemotherapy as 2nd line treatment of advanced gastric/gastro-oesphageal junction (GEJ) adenocarcinoma. DURIGAST PRODIGE 59 is a randomized, multicenter, phase II study designed to assess the efficacy and safety of the combination of FOLFIRI plus durvalumab (anti-PD-L1) (FD) versus FOLFIRI plus durvalumab and tremelimumab (anti-CTLA-4) (FDT). Key eligibility criteria included advanced gastric/GEJ adenocarcinoma, platinum-based first-line chemotherapy and ECOG performance status 0 or 1. The primary endpoint is progression-free survival (PFS) at 4 months, which was expected to be 70%. Secondary endpoints included safety, overall survival (OS) and quality of life. Between August 2020 and June 2021, 96 patients were randomized, 48 in each arm. The median age was 59.7 years, 30.4% were women and 66.3% were ECOG PS 1. Half of patients had gastric tumors (50.0%), mostly with synchronous metastases (65.2%) and doublet first-line chemotherapy (63.0%). Only 4.3% were dMMR/MSI. The 4-month PFS were 44.7% [90%CI: 32.3–57.7] and 55.6% [90%CI: 42.3–68.3] in the FD and FDT arms, respectively. Median PFS were 3.8 and 5.4 months, objective response rates were 32.6% and 37.7% and median OS was 13.3 and 9.5 months in FD and FDT arms, respectively. However, a remarkable disease control over 1 year was observed in FDT arm (n=7, 15.2%) as compared FD arm (n=2, 4.3%). Grade 3-4 adverse events related to the treatment were 47.8% in each arm (asthenia: 17.4% vs 23.9%, neutropenia: 15.2% vs 23.9%, anemia: 10.9% vs 6.5%, diarrhea: 2.2% vs 10.9% and vomiting: 6.5% vs 2.2% in FD and FDT arms, respectively). Combination of immune checkpoint inhibitors plus FOLFIRI in 2nd line treatment for advanced gastric/GEJ adenocarcinoma demonstrates an acceptable safety profile. Despite a negative result for the entire population, this combination seems to be very active in a sub-group of patients. Predictive factors of efficacy are currently explored, and will be presented during ESMO meeting.