Efficacy and safety of surufatinib and sintilimab with or without chemotherapy for advanced high-grade neuroendocrine neoplasms and pancreatic cancer.

Neuroendocrine carcinoma (NEC), neuroendocrine tumor grade 3 (NET G3), and pancreatic cancer (PC) are aggressive malignancies with limited effective treatments. This study assessed the efficacy and safety of surufatinib combined with the PD-1 inhibitor sintilimab, with or without chemotherapy. In this phase II trial, 51 patients with advanced NEC (n = 30), NET G3 (n = 12), or PC (n = 9) received surufatinib plus sintilimab; the NEC cohort additionally received chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. As of August 31, 2025, the median follow-up was 18.6 months. In the NEC cohort, median PFS was 7.3 months, median OS was 13.3 months, and ORR was 53.3%. First-line NEC patients achieved superior outcomes (mPFS 7.6 months; mOS 14.3 months; ORR 65.0%) versus later-line therapy. Median PFS was 6.8 months in the NET G3 cohort and 2.1 months in the PC cohort. Adverse events were manageable; no treatment-related death occurred. Surufatinib plus sintilimab with or without chemotherapy shows encouraging efficacy and acceptable safety in advanced NEC, NET G3, and PC. This clinical trial was registered at ClinicalTrials.gov (NCT05627427) on November 15, 2022.