Abstract CT266: Initial efficacy of surufatinib plus sintilimab and IBI310 for patients with high-grade advanced-neuroendocrine neoplasm: A multicenter, single arm phase 2 stud

Abstract Background: High-grade advanced-neuroendocrine neoplasm (HG-NEN) are more aggressive and have worse prognosis. Surufatinib (SUR, a selective VEGFRs; FGFR1; and CSF-1R inhibitor). Ipilimumab (anti-CTLA-4) plus nivolumab (anti-PD-1) has been recommended for extrapulmonary and non-pancreatic NEC if the disease progresses following chemotherapy by the NCCN guidelines for neuroendocrine tumors. Preclinical and clinical studies have shown that SUR is a good partner of immune checkpoint inhibitors (ICIs). In this study, we present findings of SUR combined with Sintilimab (SIN, anti-PD-1) and IBI310 (IBI, anti-CTLA-4) for HG-NEN patients (pts). Methods: Pts with histologically confirmed HG-NENs who resistant or intolerant to standard treatment were included in the study. Enrolled pts received SUR (250 mg, qd, po, q3w) combined with SIN (200 mg, d1, i. v. gtt, q3w) and IBI (1 mg/kg, d1, i. v. gtt, q6w). The primary endpoint was ORR per RECIST 1. 1. The second endpoints were PFS, DCR, safety and OS. Results: By Dec 29, 2023, 14 pts were enrolled and available for efficacy assessment. Median age, 53 yrs (range 22- 66) ; male, 71. 4%; ECOG PS 1, 50%; GEP-NEN, 57. 1%; NEC, 71. 4%; Median ki-67 index, 65% (range 25%-90%) ; liver metastases, 57. 1%. 85. 7% pts received prior systemic therapy (50% 1L and 35. 7% ≥2L). Confirmed ORR was 28. 6% and DCR 76. 8%. Median PFS was 4. 15 months. Among 9 pts with ≤1 prior systemic regimens, confirmed ORR and DCR were 44. 4% and 88. 9%, respectively, with a median PFS of 4. 5 months. Out of 14 pts, all experienced some form of treatment- emergent events (TEAEs), with only 3 participants (21. 4%) reporting grade 3 TEAEs. These included manageable events like increased bilirubin, immune pancreatitis, gastric retention, and increased amylase, each with a 7. 1% incidence. No grade 4 TEAEs or new safety signals occurred. Conclusion: Surufatinib combined with Sintilimab and IBI310 showed a potential antitumor activity and a tolerable safety profile, providing an additional treatment option for pts with high-grade NEN. Citation Format: Panpan Zhang, Yakun Wang, Jie Li, Lin Shen, Ming Lu. Initial efficacy of surufatinib plus sintilimab and IBI310 for patients with high-grade advanced-neuroendocrine neoplasm: A multicenter, single arm phase 2 stud abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr CT266.