Multicenter randomized phase 2 trial of nivolumab with or without ipilimumab for pretreated advanced neuroendocrine carcinoma

There is no standard second-line therapy for gastroenteropancreatic (GEP) and lung large-cell neuroendocrine carcinoma (NEC) after failure of platinum-based chemotherapy. The multicenter GCO-001 NIPINEC noncomparative randomized phase 2 trial in France evaluated nivolumab with or without ipilimumab in this setting. The trial included adult patients with performance status 2 or better, advanced large- and small-cell GEP-NEC and large-cell lung NEC, after one or two previous lines of therapy for NECs refractory to platinum-based chemotherapy. Patients were randomized (1:1) to nivolumab alone (n=91) or nivolumab plus ipilimumab (n=94) for 2 years or until progression or unacceptable toxicity. The primary endpoint was investigator-assessed objective response rate (ORR) at 8 weeks, being 7.2% (95% CI 2.7-15.1) in the nivolumab arm and 14.0% (7.4-23.1) in the nivolumab plus ipilimumab arm. The best ORR was 9.6% and 20.9%, respectively, whereas the median progression-free survival and overall survival were approximately 2 months and 6 months in both arms. One treatment-related death occurred in the nivolumab arm, while grade 3-4 adverse events in the nivolumab plus ipilimumab arm were asthenia (13%, gamma-glutamyl transferase increase (10%), alkaline phosphatase increase (9%), dyspnea (7%), and anemia (6%). The authors conclude that nivolumab plus ipilimumab could be an second- or third-line option for NECs.