Sintilimab, doxorubicin and ifosfamide (AI) as first-line treatment in patients with advanced undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), myxoid liposarcoma (MLPS) and de-differentiated liposarcoma (DDLPS): A single-arm phase 2 trial.

11505 Background: Anti-PD-1 antibody had showed encouraging activity as salvage treatment in patients with certain subtypes of advanced soft tissue sarcoma. However, its role in first-line setting is uncertain. We assessed the safety and activity of sintilimab, an anti-PD-1 antibody, combined with doxorubicin (ADM) and ifosfamide (IFO) in patients with advanced undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), myxoid liposarcoma (MLPS) and de-differentiated liposarcoma (DDLPS). Methods: This is a single-arm, phase 2 study. Systemic treatment naïve patients with metastatic or unresectable locally advanced UPS, SS, MLPS and DDLPS were treated with sintilimab (200mg, d1), ADM (60mg/m 2 , d1) and IFO (1.8 g/m 2 /d, d1-5) every 3 weeks for up to 6 cycles, followed by sintilimab maintenance until disease progression, unacceptable toxicities or up to 2 years. The primary endpoint was objective response rate (ORR, per RECIST 1.1), and secondary endpoints included progression free survival (PFS), overall survival (OS) and safety. Results: Between June 2020 and June 2023, 46 eligible patients were enrolled. 31 were male, and the median age was 47 years old. Of the 41 evaluable pts, ORR was 68.3% (28/41), including 7/8 (87.5%) UPS, 13/20 (65.0%) SS, 3/3 (100%) MLPS and 5/10 (50%) DDLPS patients. At a median follow-up time of 28.0 months (95% CI: 9.4-46.7 months), the median PFS and OS were 9.0 months (95% CI: 6.5-11.5 months) and 19.9 months (95% CI: 14.9-24.9 months), respectively. 1 DLT was observed in the first six patients during the DLT observation window. The most frequent ≥ grade 3 adverse events were leucopenia (50.0%), neutropenia (45.7%), thrombocytopenia (21.7%), anemia (21.7%), and febrile neutropenia (21.7%). Conclusions: The primary endpoint of ORR was met. This study indicated promising efficacy and safety of sintilimab combined with AI in the first-line treatment of UPS, SS, MLPS and DDLPS. Clinical trial information: NCT04356872 .