Phase II study to evaluate surufatinib in patients with osteosarcoma and soft tissue sarcoma that has failed standard chemotherapy: Updated analysis.

11539 Background: In this single-arm, open-label, multi-center, phase II study (NCT05106777) primary analysis, surufatinib (a multi-targeted, small-molecule inhibitor of VEGFR-1, 2, 3, FGFR-1 and CSF-1R) demonstrated some clinical activities for osteosarcoma and soft tissue sarcoma (STS) patients (pts) who have failed in standard chemotherapy at the 2023 ASCO (e23540). Herein, we reported the updated efficacy and safety data with more enrolled pts. Methods: Pts aged 14-70 years (pts ≤ 18 years have a body surface area of ≥1.5m 2 ) with advanced, unresectable or metastatic osteosarcoma and STS who failed or intolerance to standard chemotherapy, ECOG PS 0-1, RECIST 1.1 measurable lesion were enrolled. A Simon optimal 2-stage design was used. If ≥ 3/13 had no disease progression at 12 weeks in stage 1, the study would proceed to stage 2, and ≥ 12/43 achieved the primary endpoint, the study would be successful. Enrolled pts received surufatinib 300 mg, QD, PO in a 21-days cycle. Primary endpoint was progression-free rate at 12 weeks (PFR 12weeks ). Secondary endpoints were PFS, ORR, DCR, OS and safety. Results: As of 31 Dec, 2023, 43 pts (median age, 48 years [range, 22-68]) were included. 51% were male and 70% had ECOG PS 1. 46.5% received ≥ 2 lines of prior therapy (range, 2-7). The main tumor histologic subtypes included 11 leiomyosarcoma (LMS), 8 liposarcoma (LPS), 4 synovial sarcoma (SS), 4 fibrosarcoma (FS) and others. Among the 41 evaluable pts, 21 pts had no disease progression at 12 weeks and PFR 12weeks was 51.22%. ORR in 21 pts who received surufatinib as 2L therapy was 19.05% (1 CR, 3 PR). DCRs of 2L or 3L and later-line therapy were 90.48% (19/21) and 80% (16/20). The ORRs of main subtypes were 20% (2/10) in LMS and 12.5% (1/8) in LPS, respectively. After median follow up of 9.92mo, the median PFS was 5.68mo (95%CI, 4.27-12.68) for 2L pts, while 2.74mo (95%CI, 2.63-3.12) for 3L and later-line therapy pts. In main subtypes, the PFS was 7.13mo (95%CI, 2.76-NA) for LMS and 3.78mo (95%CI, 2.73-9.99) for LPS. Compared with pts who received anlotinib in prior therapy, pts without anlotinib showed longer PFS (3.07mo vs 4.27mo, p=0.1215). Treatment related adverse events (TRAEs) were mostly mild (grade 1-2), the most common including proteinuria (75%), hypertension (60%), hypertriglyceridemia (60%), diarrhea (40%), hyperbilirubinemia (40%) and urine occult blood (40%). Grade 3-4 TRAEs were recorded in 16 pts including hypertension, proteinuria, hypertriglyceridemia, hyperbilirubinemia. Conclusions: The updated results continued to support the clinical activity of surufatinib as second-line therapy in advanced osteosarcoma and STS who failed in standard chemotherapy with long-term follow-up, while the safety profile remained satisfactory, especially for LMS pts. Surufatinib might be a potential second-line option for pts with advanced osteosarcoma and soft tissue sarcoma. Clinical trial information: NCT05106777 .