Multicenter phase II study of anlotinib and toripalimab in patients with advanced soft tissue sarcoma (STS) and bone sarcoma (BS).

11556 Background: This multicenter phase II study aims to evaluate the efficacy and safety of anlotinib combined with toripalimab in the treatment of patients (pts) with advanced STS or BS. Methods: Pts with advanced STS or BS, 14-70 years, at least one measurable tumor lesion per RECIST 1.1 and failure or intolerance of standard systemic therapy, or no standard treatment existed, are eligible. Pts with alveolar soft-part sarcoma (ASPS) and clear cell sarcoma (CCS) can be included as the first-line therapy. Anlotinib (12 mg/d, po, d1-14) and toripalimab (240mg, IV, d1) would be administered every 3 weeks. The primary endpoint was investigator-assessed objective response rate (ORR). The secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety using NCI-CTCAE v4.03. Results: Between March, 2020 and November, 2024, 70 pts were enrolled, of whom 68 were evaluable for the efficacy analyses. The STS subtypes mainly included synovial sarcoma (SS, 15.7%), rhabdomyosarcoma (RMS, 8.6%), extraskeletal Ewing's sarcoma (EES, 7.1%), epithelioid sarcoma (EpS, 7.1%), leiomyosarcoma (LMS, 7.1%), ASPS (5.7%), liposarcoma (5.7%), undifferentiated sarcoma (5.7%) and others (31.4%). The BS subtypes included 2 (2.9%) osteosarcoma and 2 (2.9%) chondrosarcoma. With a median follow up of 29.1 months, partial response occurred in 19 pts: 4 with SS, 3 with ASPS, 2 with LMS, 2 with EpS, 2 with inflammatory myofibroblastic tumor, and one patient each with RMS, EES, undifferentiated sarcoma, CCS, malignant peripheral nerve sheath tumor, or desmoplastic small round cell tumor. The ORR and DCR for the entire cohort were 27.9% and 86.8%, respectively. The median PFS was 7.0 months (95% CI: 4.2-9.8). The median OS was 23.5 months (95% CI: 9.2-37.8). For the 64 efficacy-evaluable STS cohort, the ORR was 29.7% and the median PFS was 8.1 months (95% CI: 4.7-11.5). Most of the treatment-related adverse events were mild (grade 1-2). The most common grade 3/4 adverse events (AE) were hypertension (15.7%), hand-foot syndrome reaction (12.9%), and hypertriglyceridemia (7.1%). Conclusions: The combination of anlotinib and toripalimab showed good anti-tumor activity and durable efficacy in advanced STS patients, with acceptable toxicity. Clinical trial information: NCT04172805 .