496MO Final Overall Survival Results from the NICE-NEC Trial (GETNE-T1913): A Phase II Study of Nivolumab and Platinum-Doublet Chemotherapy (CT) in Untreated Advanced G3 Neuroendocrine Neoplasms (nens) of Gastroenteropancreatic (GEP) or Unknown (UK) Origin

G3 NENs are aggressive tumors with a median overall survival (OS) of ∼11 months (m) with standard platinum-based front line CT. Their high mutational burden and PD-L1 overexpression position G3 NENs as potential candidates for immunotherapy. The aim of this study was to assess the efficacy of the combination of CT plus Nivolumab (Niv) in patients (pts) with advanced CT-naïve G3 NENs. NICE-NEC is an open-label, non-randomized, phase II trial that recruited pts with metastatic or locally advanced unresectable G3 NENs of GEP/UK origin. Pts received Niv 360mg d1, Carboplatin AUC 5 d1, Etoposide 100mg/m2 d1-3 Q3W (up to 6 cycles) followed by Niv 480mg Q4W (up to 24 m). Primary endpoint was 12-m overall survival (OS) rate. Secondary endpoints included objective response rate (ORR), progression-free survival (PFS) and safety. From 2019 to 2021, 38 pts were enrolled. Median age was 61 years, 68% male, 89.4% ECOG 0-1, 68.4% were poorly differentiated, 65.8% had Ki67 >55%, 94.7% stage IV at diagnosis, and 74% had ≥2 organs involved. With a median follow-up of 18.6 m (range: 2.2-24.6) for alive pts, ORR was 54.1%, DCR 83.8% and median PFS was 5.7 m (95%CI: 5.1-9). Throughout the study period, 21 (56.8%) pts died. Median OS was 13.9 m (95%CI: 8.3-NR) with an estimated cumulative survival ratio of 53.8% (95%CI: 39.8-72.6) / 44% (95%CI: 30.1-64.2) at 12/18 m. 12 (32.4%) pts were long survivors (OS >18 m). The 12-m OS rate was 46.7% vs 59.3% for Ki-67 ≤55 and >55, respectively (p=0.513); and 58.3% vs 54.7% for well and poorly differentiated, respectively (p=0.773). Median OS was 6.4 m for colorectal, 14.6 m for pancreatic, and not reached for esophago-gastric / small bowel NENs. The combination of CT plus Niv shows promising activity and prolonged survival benefit in a subset of pts with GEP/UK primary G3 NENs. Randomized trials are warranted to confirm treatment benefit. Ongoing translational studies may help identify predictive/prognostic biomarkers to improve selection of pts most likely to benefit from this treatment strategy.