A Phase II Study of Surufatinib in Patients with Osteosarcoma and Soft Tissue Sarcoma Who Have Experienced Treatment Failure with Standard Chemotherapy

e23540 Background: Surufatinib is a multi-targeted, small-molecule tyrosine kinase inhibitor (TKI) that shows strong inhibitory effect on the activity of VEGFR-1, 2, 3, FGFR1 and CSF-1R. Here we conducted this trial to explore the efficacy and safety of surufatinib in the treatment for osteosarcoma and soft tissue sarcoma (STS) patients (pts) who have failed in standard chemotherapy. Methods: Pts with advanced osteosarcoma and STS (unresectable or metastatic), 14-70 years, and ECOG PS 0-1, are eligible. Surufatinib 300 mg q.d. is given in a 21-days schedule. Progression-free rate at 12 weeks (PFR 12weeks ) was the primary endpoint. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety (NCT05106777). Results: As of December 30, 2022, 19 pts (male, n=12; median age, 44 years [range, 23-67]; median lines of prior therapy, 2 [range, 2-5]) were enrolled. The most common histological subtypes included 3 leiomyosarcoma, 3 liposacroma, 3 epithelioid hemangioendothelioma, 2 fibrosarcoma and other. The interim analysis revealed 7 pts with stable disease (SD) and 1 pt with partial response (PR) at 12 weeks in stage 1. Recruitment was continued in stage 2 as initially planned. With 15 pts for efficacy analysis, PFR 12weeks was 60% (9 pts). Best objective response by RECIST 1.1 was complete response (CR) in 1 pt (ORR of 6.7%) and SD in 11 pts (DCR of 80%). With a median follow-up of 6.97 months (95%CI: 5.28-8.65), the median PFS was 5.7 months (95%CI: 1.07-10.30). Treatment emergent adverse events (TEAEs) were mostly mild (grade 1-2), and the most common were hypertension (80%), proteinuria (73%), hypertriglyceridemia (53%), diarrhea (47%) and hyperbilirubinemia (47%). Grade 3-4 TEAEs were recorded in 4 pts including hypertension, proteinuria, hypertriglyceridemia and hypermagnesemia. Conclusions: Surufatinib is well tolerated and have some clinical activity in advanced osteosarcoma and STS who failed standard chemotherapy. Enrollment is ongoing and updated data will be presented in the future. Clinical trial information: NCT05106777 .