Surufatinib Plus Toripalimab in Patients with Advanced Neuroendocrine Tumours and Neuroendocrine Carcinomas: an Open-Label, Single-Arm, Multi-Cohort Phase II Trial

Background: The programmed death 1 inhibitor toripalimab plus the angio-immuno kinase inhibitor surufatinib revealed a tolerable safety profile and preliminary efficacy in patients with advanced solid tumours in a phase I study. Patients and methods: This was an open -label, single -arm, multi -cohort phase II study in China. Patients with advanced neuroendocrine tumours (NETs) or neuroendocrine carcinomas (NECs) or mixed neuroendocrine nonneuroendocrine neoplasms (MiNENs) who had failed or were intolerable of standard treatment were given surufatinib (250 mg orally, once daily) plus toripalimab (240 mg intravenously, once every 3 weeks). Primary end -point was investigator -assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end -points included duration of response (DoR), disease control rate, progressionfree survival (PFS), overall survival (OS), and safety. Results: Forty patients were enrolled into two cohorts by tumour types (NET, n = 19; NEC-MiNEN, n = 21). ORRs (95% CIs) were 21.1% (6.1-45.6) and 23.8% (8.2-47.2) in the NET and NEC-MiNEN cohorts, respectively. Median DoR was 7.1 months (6.9-not evaluable [NE]) and 4.1 months (3.0-NE), respectively. Median PFS was 9.6 months (4.1-NE) and 4.1 months (1.5-5.5); median OS was 27.3 (15.3-NE) and 10.9 months (9.1-14.6), respectively. Overall, grade >= 3 treatment -related adverse events occurred in 18 (45.0%) patients. Conclusions: Surufatinib plus toripalimab showed antitumour activity and a tolerable safety profile in patients with previously treated NETs/NECs/MiNENs. Further study of this combination regimen is ongoing for advanced NECs, for which current therapeutic options remain limited. ClinicalTrials.gov: NCT04169672