Efficacy and safety of surufatinib, a novel dual-mechanism inhibitor, as a second-line or further treatment in advanced sarcoma: a multicenter, single-arm, phase 2 trial

Patients with advanced, treatment-refractory sarcoma face a poor prognosis and limited options following failure of standard therapies. This study evaluated the efficacy and safety of surufatinib, a novel inhibitor targeting vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), and colony-stimulating factor-1 receptor (CSF-1R), in patients with advanced sarcoma who had failed standard therapy. In this multicenter, single-arm, phase 2 trial, patients with unresectable or metastatic sarcoma who had received prior treatment were enrolled and received surufatinib 300 mg once daily. The primary endpoint was the 12-week progression-free rate (PFR 12w ). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). As of September 30, 2025, the median follow-up was 27.5 months among 47 enrolled patients; 46.8% had received ≥ 2 prior lines of therapy. In 45 evaluable patients, the PFR 12w was 71.1%. The ORR was 11.1%, including one complete response in a patient with angiosarcoma, and the DCR was 86.7%. Median PFS was 4.3 months, with significantly longer PFS when surufatinib was used as second-line therapy compared with later lines (5.7 vs. 2.8 months; p < 0.001). Patients with non-uterine leiomyosarcoma also showed improved PFS (median: 7.2 vs 4.2 months; p = 0.024). Prior exposure to anti-angiogenic therapy did not impact PFS (median: 3.3 vs. 4.3 months; p = 0.924). Median OS was not reached, with 1- and 2-year OS rates of 82.2% and 63.9%, respectively. Grade ≥ 3 treatment-related adverse events occurred in 29.8% of patients. These findings indicate that surufatinib has preliminary antitumor activity and a manageable safety profile in advanced sarcoma, even after prior anti-angiogenic therapy. The encouraging efficacy observed in the second-line setting and in non-uterine leiomyosarcoma provides a rationale for continued clinical development. ClinicalTrials.gov: NCT05106777. ClinicalTrials.gov ( http://www.clinicaltrials.gov/ )