2264 - A Phase Ib/II Trial of Radiotherapy Combined with Doxorubicin and Sintilimab for Localized High-Risk Limbs and Trunk Soft Tissue Sarcomas

02:30pm - 04:00pm PT

Hall F

Screen: 34

POSTER

Presenter(s)

Yan WANG, MD, PhD - Fudan University Shanghai Cancer Center, Shanghai, Shanghai

Y. WANG^1,2, S. Zhou^1,2, L. Xu^1,2, Y. Su^1,2, Y. Wang^1,2, R. WU^1,2, L. Shen^1,2, J. Wan^1,2, Y. Xu^2,3, Y. Chen^2,3, W. Yan^2,3, and Z. Zhang^1,4; ¹Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, ²Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China, ³Department of Musculoskeletal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China, ⁴Department of Radiation Oncology, Fudan University Shanghai Cancer Center, ???, China

Purpose/Objective(s):

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, 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.

Materials/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 (doxorubicin/hydroxydaunorubicin, 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 February 2025, 33 patients with localized high-risk STSs (26 in limbs and 7 in trunks) were enrolled. The median age was 50 years (range 19-75), with 17 (51.5%) males, and 13 (39.4%) patients had prior surgeries. 29 (87.9%) 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 31 evaluable patients, 2 achieved complete response (CR), 14 achieved partial response (PR), and 12 had stable disease, resulting in an ORR of 51.6% (16/31) and a disease control rate (DCR) of 90.3% (28/31). In addition, among 26 pathological assessable patients, 14 (53.8%) achieved pCR or near-pCR. Two patients experienced major wound complications. They underwent secondary operation and readmission to hospital for wound care, respectively. Other serious adverse events (SAE) include Grade 3 dermatitis (16.1%) and Grade 3-4 neutropenia (9.7%). No G5 SAE were reported. Median progression-free survival and overall survival 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.