SBRT Combined With Reduced-Dose Anthracycline Chemotherapy and Toripalimab as Neoadjuvant Therapy for Localized High-Risk Undifferentiated Pleomorphic Sarcoma

Summary

This is a prospective, single-center, single-arm, open-label phase II exploratory study to evaluate the efficacy, safety, and immune remodeling effects of stereotactic body radiotherapy (SBRT) combined with reduced-dose anthracycline chemotherapy and the PD-1 inhibitor toripalimab as neoadjuvant therapy, followed by postoperative stratified maintenance therapy, in patients with localized high-risk undifferentiated pleomorphic sarcoma (UPS). A Simon two-stage design will be used, with 39 patients planned (stage 1: 13 patients; 35 patients in total, including a 10% dropout rate). Treatment consists of SBRT (8-10 Gy in 5 fractions) followed by toripalimab (240 mg intravenously every 3 weeks, 3 cycles in the neoadjuvant phase) combined with liposomal doxorubicin (30-40 mg/m² intravenously every 3 weeks, 2 cycles in the neoadjuvant phase). After response evaluation, radical surgery is performed. Postoperative stratified maintenance therapy is delivered according to pathological response: patients achieving major pathologic response (MPR) or hyalinized pathologic response (HPR) receive toripalimab monotherapy (240 mg every 3 weeks, up to 14 cycles), while those not achieving MPR/HPR receive toripalimab combined with liposomal doxorubicin (2-4 cycles). The primary endpoint is the rate of major pathologic response (MPR). Secondary endpoints include the rate of hyalinized pathologic response (HPR), radiologic objective response rate (ORR), R0 resection rate, limb salvage rate, and safety.

Timeline

Start

2026-09

Primary completion

2029-01

Completion

2030-09

Drugs

Indications