(P 136) PRELIMINARY EFFICACY AND SAFETY OF FAMITINIB PLUS SHR-1701 IN ADVANCED SARCOMA: A SINGLE-CENTER, PHASE 2 TRIAL

Objective: Angiogenesis inhibitors combined with immune checkpoint inhibitors have shown synergistic anti-tumor activity in soft tissue sarcoma. We investigated the safety and efficacy of famitinib, a tyrosine kinase inhibitor (TKI) of angiogenesis, combined with the bifunctional fusion protein SHR-1701 targeting PD-L1 and TGF-β in patients (Pts) with chemotherapy-refractory sarcoma.

Methods: Pts were eligible if they were aged 12 years or older, and had histologically confirmed advanced or metastatic sarcomas; the presence of measurable disease according to RECIST 1.1; an ECOG performance status of 0-1; progressive disease after at least one line of adriamycin containing chemotherapy; MSI-H or TMB>5 or PD-L1≥1% except for alveolar soft-part sarcoma (ASPS) and undifferentiated pleomorphic sarcoma (UPS). Pts received famitinib (20 mg/day, PO) combined with SHR-1701 (30mg/kg, iv, q3w) until disease progression or unacceptable toxicity in this phase 2, single-center, open-label, Simon's optimal two-stage design study. Success at stage 1 required ≥3 pts remaining progression-free at 12 weeks. Success at stage 2 required ≥7 pts remaining progression-free at 12 weeks. The primary endpoint was progression-free survival (PFS) at 12 weeks. Clinical trial identification: ChiCTR2100046099.

Results: Between May 2021, and April 2022, a total of 8 pts were assessed for eligibility, 6 (median age of 34 years; 5 females; all patients had undergone at least 3 lines of anti-tumor treatment; n=3, ASPS; n=1, UPS; n=1, leiomyosarcoma; n=1, Ewing-like sarcomas (ELS) with CIC gene fusion) pts were eligible. 50% pts received anti-angiogenesis treatment and 33% pts received anti-PD-1 therapy before enrollment. With a median follow-up of 8.4 months, 3pts remained progression-free at 12-weeks. Futility was passed for stage 1. Adverse events (AEs) were generally mild. The most common treatment-related AEs were hypothyroidism (50%), anemia (33.3%), thrombocytopenia (33.3%), epistaxis (33.3%), gingival bleeding (33.3%), menometrorrhagia (16.7%), proteinuria (16.7%)，alanine aminotransferase increased (16.7%) and aspartate aminotransferase increased (16.7%). The most common grade 3 or above AEs included proteinuria (16.7%), anemia (16.7%), and gamma-glutamyl transferase increased (16.7%). No serious treatment-related AE and death were observed.

Conclusion: Famitinib plus SHR-1701 has manageable toxicity and preliminary activity in pts with advanced sarcomas, warranting further investigation.