(P 119) UPDATED RESULTS OF A SINGLE-ARM,MULTI-CENTER STUDY OF ANLOTINIB COMBINED WITH TORIPALIMAB IN FIRST-LINE TREATMENT OF UNRESECTABLE OR METASTATIC UNDIFFERENTIATED PLEOMORPHIC SARCOMA

Objective: Undifferentiated pleomorphic sarcoma (UPS) is one of the common subtypes of soft tissue sarcoma (STS). Alternative therapy is needed for patients who are not suitable for chemotherapy. Antiangiogenic agents are approved for the treatment of advanced STS. In the SARC028 study, PD-1 inhibitor showed initial efficacy on UPS. The combination of antiangiogenic agent and PD-1 inhibitor may have synergistic effects. This single-arm phase II study aims to evaluate the efficacy and safety of anlotinib combined with toripalimab in the first-line treatment of patients with unresectable or metastatic UPS.

Methods: This study planned to recruit 25 eligible patients who refused chemotherapy in the first line of treatment. All patients would receive anlotinib (12 mg/d, PO, d1-14) combined with toripalimab (240mg, IV, d8) on the first 28-day cycle. From the second cycle, anlotinib (d1-14) and toripalimab (d1) would be administered every 3 weeks. The primary endpoint was progression-free rate (PFR) on 3 months (PFR3m). The secondary endpoints include overall response rate (ORR) , disease control rate (DCR) , overall survival (OS), and safety. The correlation between tumor immune microenvironment and clinical efficacy would be explored simultaneously.

Results: From November 2019 to June 2024 , 17 patients were recruited, 13 patients had at least one tumor assessment and were included in the Per-Protocol Set (PPS). The median follow-up time was 14.9 m (range from 1.64 to 32.9 m), and the PFR3m is 76.92%. ORR is 61.54% (95% CI, 35.09% to 87.99%). DCR is 84.62% (95% CI, 65.0% to 104.23%). Preliminary median OS is 22.14 months . The overall incidence of adverse events (AEs) was 100%, common AEs included hypertension, hand-foot skin reaction, and mouth pain. Highly expressed PD-L1 (>50%) and T cells and monocyte/macrophage infiltrating was found in a PR patient. Activated CD8+ T cells and PD-L1 high-expressing cells also showed co-localization. (Detailed result in the table).

Conclusion: Anlotinib combined with toripalimab showed good anti-tumor activity in unresectable or metastatic UPS patients, with acceptable toxicity, and the correlation between the efficacy and the tumor microenvironment is still under exploration.