Abstract 499TiP
Background
Surufatinib (SUR) is a small molecule kinase inhibitor that primarily acts on VEGFR 1, 2, 3, fibroblast growth factor receptor 1 (FGFR 1), and colony-stimulating factor 1 receptor (CSF-1R). It has recently been approved for the treatment of patient (pts) with extrapancreatic (ep) NETs and pancreatic (p) NETs in China. Preclinical studies have demonstrated that SUR decreased M2 tumor-associated macrophages (TAMs) and increased M1 TAMs, and enhanced antitumor effect when SUR is combined with immune checkpoint inhibitors (ICI). Additionally, SUR plus toripalimab (anti-PD-1) was well tolerated, and showed preliminary anti-tumor activity in patients with high-grade advanced-neuroendocrine neoplasm. Given potential synergism between SUR and ICI, we hypothesized that the combination of SUR and Sintilimab (SIN, anti-PD-1) and IBI310 (IBI, anti-CTLA-4) would benefit pts with superior efficacy. Herein, we designed this study to assess the safety and clinical activity of SIN-IBI with SUR as first- or second- line therapy for advanced grade-3 neuroendocrine tumor (G3 NET) and neuroendocrine carcinoma (NEC) pts.
Trial design
This is a single arm, open-label, multicenter study for high-grade advanced-neuroendocrine neoplasm, enrolling up to 40 patients with unresectable lesions, who fails or cannot tolerate standard therapies, or have no standard treatment plan. Pts must have ECOG performance status 0 or 1, and an expected survival exceed 12 weeks. All patients will be treated with SUR (250mg, qd, po, q3w) combined with SIN (200mg, d1, i.v.gtt, q3w) and IBI (1mg/kg, d1, i.v.gtt, q6w). The primary endpoint is objective response rate (ORR, RECIST 1.1). Secondary endpoints are ORR (iRECIST 1.1), disease control rate (DCR, RECIST 1.1 & iRECIST 1.1), progression-free survival (PFS), duration of response (DoR) and survival time (OS). Adverse events (AEs) and serious AEs will be monitored throughout the study and for 90 days after treatment. Cox proportional hazards model was used to identify the prognostic value of PD-L1. Exploratory analyses of drug-resistance will be conducted using tumor and blood samples collected during screening and at progression.
Clinical trial identification
NCT05165407, December 21, 2021.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Hutchmed.
Disclosure
All authors have declared no conflicts of interest.