ESTRO 2025 - Abstract Book

S1665

Clinical - Sarcoma & skin cancer & malignant melanoma

ESTRO 2025

907

Proffered Paper A Phase Ib/II Trial of Radiotherapy Combined with Doxorubicin and Sintilimab for Localized High-Risk Limbs and Trunk Soft Tissue Sarcomas Yan WANG 1 , Shujuan ZHOU 1 , Lanyue XU 1 , Yue SU 1 , Yaqi WANG 1 , Ruiyan WU 1 , Lijun SHEN 1 , Juefeng WAN 1 , Yu XU 2 , Yong CHEN 2 , Wangjun YAN 2 , Zhen ZHANG 1 1 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. 2 Department of Musculoskeletal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China Purpose/Objective: Localized high-risk soft tissue sarcomas (STSs) presents a therapeutic challenge due to limited preoperative treatment options. Radiotherapy (RT) and Doxorubicin (DOXO) are well-established immunogenic cell death inducers [1-3], which are capable of boosting the efficacy of immunotherapy even in "cold" tumors. This study aims to evaluate the safety and efficacy of a preoperative triple combination of RT, DOXO, and the PD-1 antibody (SIN) for STS. Material/Methods: In this Phase Ib/II trial (NCT05774275), up to 52 patients will be enrolled. Participants will receive RT (BED=50-60 Gy), combined with DOXO and SIN (200 mg, Day 1) every three weeks for four cycles prior to surgery. In Phase Ib (3+3 design), patients will receive Pegylated liposomal doxorubicin (PLD, 37.5 mg/m² or 30 mg/m², i.v., Day 1) to establish the recommended Phase 2 dose (RP2D). In Phase II, DOXO will be administered as PLD at RP2D or as Doxorubicin Hydrochloride (Adriamycin, ADM, 75 mg/m² i.v., Day 1). The primary endpoint is the objective response rate (ORR), while secondary endpoints include the rate of pathological complete response (pCR) and near pCR (defined as <10% viable tumor cells), survival, and safety. Results: From September 2022 to October 2024, 27 patients with localized high-risk STSs (20 in limbs and 7 in trunks) were enrolled. The median age was 49 years (range 19-75), with 14 (51.9%) males, and 8 (29.6%) patients had prior surgeries. 25 (92.6%) tumors were histological grade 3. No dose-limiting toxicities (DLT) were observed in the first six patients receiving PLD (37.5 mg/m², i.v., Day 1, q3w) with SIN, confirming the RP2D. Among the 22 evaluable patients, 2 achieved complete response (CR), 9 achieved partial response (PR), and 8 had stable disease, resulting in an ORR of 50.0% (11/22) and a disease control rate (DCR) of 86.4% (19/22). Two patients (9.5%) experienced major wound complications. They underwent secondary operation and readmission to hospital for wound care, respectively. One grade 3 dermatitis occurred in a patient with tumor on his foot. No other grade 3-5 treatment related adverse events were reported. Median progression-free survival (PFS) and overall survival (OS) have not yet been reached. Conclusion: The combination of RT, DOXO, and SIN showed potential efficacy and tolerable toxicity in high-risk localized limbs and trunk STS. The trial is still ongoing. References: [1] Ma Y, Aymeric L, Locher C, et al. Contribution of IL-17-producing gamma delta T cells to the efficacy of anticancer chemotherapy. The Journal of experimental medicine. 2011;208(3):491-503. [2] Pollack SM, Redman MW, Baker KK, et al. Assessment of Doxorubicin and Pembrolizumab in Patients With Advanced Anthracycline-Naive Sarcoma: A Phase 1/2 Nonrandomized Clinical Trial. JAMA oncology. 2020;6(11):1778 82. [3] Yvonne MM , Karla VB , Angela MH , et al. SU2C-SARC032: A randomized trial of neoadjuvant RT and surgery with or without pembrolizumab for soft tissue sarcoma. J Clin Oncol 42, 2024 (suppl 16; abstr 11504) Keywords: preoperative, radiotherapy, immunotherapy