Updated results from a multicenter, single-arm phase II study of surufatinib plus sintilimab and IBI310 in patients with high-grade advanced-neuroendocrine neoplasm (HG-NEN).

e16342 Background: HG-NEN are highly aggressive and associated with poor prognosis. Surufatinib (SUR), a selective inhibitor of VEGFRs, FGFR1, and CSF-1R, has emerged as a promising therapeutic agent in combination with immune checkpoint inhibitors (ICIs) based on preclinical and clinical studies. Ipilimumab (anti-CTLA-4 antibody) plus nivolumab (anti-PD-1 antibody) is recommended by the NCCN guidelines for extrapulmonary and non-pancreatic neuroendocrine carcinomas (NEC) that progress after chemotherapy. This study aims to evaluate the efficacy and safety of SUR plus sintilimab (SIN, an anti-PD-1 antibody) and IBI310 (IBI, an anti-CTLA-4 antibody) in patients (pts) with advanced grade-3 neuroendocrine tumors (G3 NETs) and NECs. Methods: Eligible HG-NEN pts included those who had failed, could not tolerate, were not suitable for, or refused to receive standard treatment. Pts received 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 was ORR. Secondary endpoints included PFS, OS, DCR and safety. ORR and DCR were based on the efficacy evaluable analysis set (EEAS) - all pts who received ≥ 1 doses of the study drug and had ≥ 1 valid post-baseline tumour assessments. Supportive analyses were conducted for the full analysis set (FAS) population. Baseline characteristics, safety, PFS, and OS were analysed in the FAS population. Results: As of Jan 06, 2025, 31 pts were enrolled, with 5 withdrawn due to drug intolerance (3 immune myocarditis, 1 immune pancreatitis, 1 thrombocytopenia) and 2 due to tumor-related SAEs. The EEAS included 24 pts, and the FAS included all 31 pts. Median age was 55 years (range: 22–71), with 67.7% male, 61.3% ECOG PS 1, and 93.5% with NEC. Median ki-67 was 80% (range: 25%-90%), with 77.4% ki-67 > 55%. 90.3% pts received prior systemic therapy (51.6% 1L and 38.7% ≥2L). The median follow-up time was 16.8 months. The mPFS was 3.8 (95% Cl: 2.8-4.5) months, with an ORR of 37.5% and DCR of 75%. The mOS was not reached. The 12-month OS rates were 63.1% and 76.6% in the FAS and EEAS population. In 15 pts who had received no more than one previous systemic regimens, the mPFS was 4.4 (95%Cl: 3.3-16.2) months, with an ORR of 46.7% and DCR of 80.0%. The 12-month OS rates were 68.4% and 82.5% in the FAS and EEAS population. 48.4% pts experienced rade ≥3 treatment-related adverse events (TRAEs). Conclusions: Surufatinib combined with sintilimab and IBI310 demonstrated promising efficacy and manageable safety in HG-NEN, with greater benefit observed in earlier treatment lines. This regimen may offer a new therapeutic option for patients with HG-NEN. Clinical trial information: NCT05165407 .