A phase II study to evaluate the efficacy and safety of fruquintinib combined with envafolimab in patients with advanced or unresectable locally advanced osteosarcoma and soft tissue sarcoma.

e23506 Background: There is an urgent clinical need for second-line therapy to improve survival in advanced osteosarcoma (OS) and soft tissue sarcoma (STS) patients (pts). The combination of fruquintinib (a highly selective, and potent oral inhibitor of VEGF receptor 1, 2, 3) and immune checkpoint inhibitors (ICIs) has shown promising efficacy in advanced solid tumor. So we conducted this trial to explore the efficacy and safety of fruquintinib combined with envafolimab (a PD-L1 antibody) in the treatment for advanced or unresectable locally advanced OS and STS pts. Methods: Pts with advanced or locally advanced OS or STS, 12-70 years, at least one measurable tumor lesion per RECIST V 1.1 and have failed to or refused first-line chemotherapy, are eligible (NCT05941325). Pts were administrated with fruquintinib (4mg, the dosage can be adjusted according to situation of pts, ranging from 3mg to 7mg, QD, PO, Q3W) and envafolimab (400mg, D1, subcutaneous injection, Q3W) until disease progression, death or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), 6mo-OS rate, and safety. Results: As of December 27, 2024, 14 pts (male, n = 11; median age, 32 years; median lines of prior therapy, 2 [range, 1-4]) were enrolled. The most common histological types included 5 OS, 3 synovial sarcoma and others. 6 pts had previously received VEGF TKIs including 5 with anlotinib and 1 with pazopanib. At the data cutoff, the combination treatment achieved a DCR of 100% (14 SD). Among these patients, 9 (64.29%) showed evidence of a reduction in tumor volume. The median PFS (mPFS) was estimated at 11.6 months with disease progression in 3 pts. Meanwhile, the mPFS of 6 pts who had previously received VEGF TKIs was 11.6 months. Treatment emergent adverse events (TEAEs) were mostly mild (grade 1-2), with the most common events were hypercholesteremia (57.14%), proteinuria (50%), increased thyroid stimulating hormone (42.86%), diarrhea (35.71%), hypertriglyceridemia (35.71%) and hand-foot- skin reaction (28.57%). Grade 3-4 TEAEs were recorded in 1 pt with hypertriglyceridemia. No treatment related death occurred. Conclusions: The combination of fruquintinib with envafolimab was well tolerated and demonstrated preliminary clinical activity in advanced or locally advanced OS and STS who had failed to first-line chemotherapy. Enrollment is ongoing and updated data will be presented in the future. Clinical trial information: NCT05941325 .