(P 409) PHASE 2 STUDY EVALUATING SURUFATINIB IN PATIENTS WITH OSTEOSARCOMA AND SOFT TISSUE SARCOMA WHO HAVE FAILED STANDARD CHEMOTHERAPY

Objective: Therapeutic options are limited for patients with osteosarcoma and soft tissue sarcoma (STS) who have progressed after initial chemotherapy. Surufatinib is a multi-targeted, small-molecule inhibitor of VEGFR-1, 2, 3, FGFR-1 and CSF-1R. Herein, we aim to present the efficacy and safety data of this single-arm, open-label, multi-center, phase II study (NCT05106777).

Methods: In this study, patients aged 14-70 years (patients ≤ 18 years with a body surface area of ≥1.5m2) with histologically or cytologically confirmed advanced, unresectable or metastatic osteosarcoma and STS who failed or intolerance to standard chemotherapy and have an ECOG PS of 0-1, as well as RECIST 1.1 measurable lesions were enrolled. A Simon optimal 2-stage design was utilized: if ≥ 3/13 patients showed no disease progression at 12 weeks in stage 1, the study would proceed to stage 2; success was defined as achieving the primary endpoint with ≥ 12/43 patients showing no disease progression. Enrolled patients received surufatinib at a dose of 300 mg, QD, PO in a 21-days cycle. The primary endpoint was progression-free rate at 12 weeks (PFR12weeks). Secondary endpoints were PFS, ORR, DCR, OS and safety.

Results: As of 13 May, 2024, 44 patients (median age, 49 years [range, 22-68]) were included. 50.0% were male and 70.4% had ECOG PS 1. 45.4% received ≥ 2 lines of prior therapy (range, 2-7). The main tumor histologic subtypes included 11 leiomyosarcoma (LMS), 8 liposacroma (LPS), 4 synovial sarcoma (SS), 4 fibrosarcoma (FS) and others. All 44 patients were evaluable. The ORR was 11.4% and DCR was 86.4%.Complete response was observed in 1 patient with angiosarcoma. 30 patients had no disease progression at 12 weeks and PFR12weeks was 69.76%. The median PFS was 4.27mo (95%CI, 2.84-5.70). In subgroup analysis, significant longer median PFS was observed in patients who received surufatinib as 2nd line therapy than those as 3rd line or later (6.8mo vs. 2.7mo, p=0.0029). Median OS was not reached yet. Treatment related adverse events (TRAEs) were mostly mild (grade 1-2). The most common including proteinuria (68.2%), hypertension (59.1%), hypertriglyceridemia (54.6%), diarrhea (36.4%), hyperbilirubinemia (36.4%) and urine occult blood (36.4%). Grade 3-4 TRAEs were recorded in 14 patients including hypertension, proteinuria, hypertriglyceridemia, hyperbilirubinemia and etc.

Conclusion: These results demonstrate the encouraging survival benefits and tolerable safety of surufatinib as 2nd-line therapy in advanced osteosarcoma and STS patients who failed in standard chemotherapy, suggesting that surufatinib might be a potential 2nd-line option for patients with advanced osteosarcoma and soft tissue sarcoma.