Efficacy and safety of surufatinib combined with EP regimen and serplulimab in first-line treatment of NEC.

e15123 Background: Neuroendocrine carcinomas (NEC) are more challenging than neuroendocrine tumors (NET) due to poor differentiation, aggressive invasion, and early diagnosis difficulties, often marked by local and distant metastasis at diagnosis, leading to poor outcomes. The ORR for NEC as first-line treatment with EP or EC regimens is approximately 30%, highlighting a substantial treatment gap. Surufatinib, a targeted small molecule kinase inhibitor, acts on vascular endothelial growth factor receptors (VEGFR-1/2/3), fibroblast growth factor receptor (FGFR-1), and colony-stimulating factor-1 receptor (CSF-1R). Its efficacy focuses on anti-angiogenesis and vascular normalization, alongside its role in modulating tumor-associated macrophages (TAMs) and boosting the effectiveness of immunotherapy. Methods: This single-arm, open-label, multicenter clinical study comprised a safety run-in (SR) phase and a dose-expansion (DE) phase. In the SR phase, six patients (pts) were planned to be enrolled to receive treatment with surufatinib (250 mg, QD, PO, Q3W) combined with the EP regimen (etoposide injection: 100mg/m 2 , d1-3, IV, Q3W; cisplatin: 25mg/m 2 , d1-3, IV, Q3W) and serplulimab (300mg, d1, IV, Q3W) for a maximum of six cycles, followed by a maintenance phase of surufatinib plus serplulimab until disease progression or other criteria as specified in the protocol. The dose of surufatinib in the DE phase was based on results from the SR phase. The primary endpoints were recommended Phase 2 dose (RP2D) and PFS, while secondary endpoints included ORR, DCR, OS, and safety. Results: As of December 27, 2023, this reports results from the SR phase. Six pts, median age 61.5 years (range 38-70), 66.7% male, all with ECOG performance status 1, were enrolled and completed their first treatment cycle. A majority (83.3%) had gastrointestinal-origin tumors with a median Ki-67% index of 70% (range 30%-90%). During the SR phase, one patient experienced Grade 4 hematologic toxicity (neutropenia and leukopenia) as a dose-limiting toxicity (DLT). Consequently, RP2D of surufatinib was established at 250mg for further research in the DE phase. The most common adverse events were neutropenia (50%), decreased white blood cell count (33.3%), fatigue (33.3%), and diarrhea (33.3%). Among those enrolled in the SR phase, 5 pts underwent at least one assessment of efficacy, yielding an objective response rate (ORR) of 60% and a disease control rate (DCR) of 100%, with the median progression-free survival (mPFS) not yet mature. Conclusions: Surufatinib combined with the EP regimen and serplulimab for NEC as first-line treatment showed notable efficacy and safety. The study established a phase II recommended surufatinib dose of 250mg, alongside immunotherapy and chemotherapy. Clinical trial information: NCT05747729 .