Surufatinib combined with sintilimab and IBI310 for the treatment of high‐grade advanced‐neuroendocrine neoplasms: A single arm, open‐label, single‐center, phase II study

Abstract This single‐center, open‐label, single‐arm phase II trial (NCT05165407) aimed to evaluate the efficacy and safety of surufatinib (250 mg orally once daily) combined with sintilimab (200 mg intravenously every 3 weeks) and IBI310 (1 mg/kg intravenously every 6 weeks) in patients with advanced high‐grade neuroendocrine neoplasms (HG‐NENs). The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), duration of response (DoR), progression‐free survival (PFS), overall survival (OS), and safety. As of March 28, 2025, 24 patients with measurable baseline lesions and at least one post‐treatment tumor assessment were included in the efficacy‐evaluable analysis set. The ORR was 37.5% (95% confidence interval [CI]: 18.8–59.4); DCR, 79.2% (95% CI: 57.8–92.9); and median DoR, 14.8 months. Among 31 treated patients in the full analysis set population, the median PFS was 3.81 months (95% CI: 2.79–4.50), and the median OS was 13.44 months (95% CI: 10.28–not estimable). Subgroup analyses showed improved response in patients with the following characteristics: female sex, age <55 years, ECOG performance status of 1, received ≤1 prior treatment line, without liver metastases, and <2 metastatic sites. Treatment‐related adverse events (TRAEs) occurred in 96.8% of patients; 45.2% experienced grade ≥3 TRAEs. Among them, 71.0% experienced TRAEs attributed to sintilimab/IBI310, and 87.1% to surufatinib. Serious adverse events occurred in 45.2% of patients. These findings suggest that surufatinib, IBI310, and sintilimab may offer clinical benefit with manageable toxicity in patients with advanced HG‐NENs.