Dual Inhibition of LAG-3 and PD-1 with IBI110 and Sintilimab in Advanced Alveolar Soft Part Sarcoma: A Single-Center, Phase II Trial

Abstract Background: Alveolar soft part sarcoma (ASPS) is an ultra‑rare soft tissue sarcoma. Current standard therapy with PD‑1/PD‑L1 inhibitors achieves limited response rates (<40%). Lymphocyte‑activation gene 3 (LAG‑3) is co‑expressed with PD‑1 on exhausted T cells, and dual blockade has shown synergy in some solid tumors but remains unexplored in sarcoma. This trial evaluated the efficacy of IBI110 (anti‑LAG‑3) plus sintilimab (anti‑PD‑1) in advanced ASPS. Method: This open‑label, phase II study enrolled 28 patients from July 2022 to September 2023 (median follow‑up 33.6 months). Both drugs were given intravenously at 200 mg every 3 weeks. The primary endpoint was overall response rate (ORR) by RECIST v1.1. Results: Among 28 patients, 8 (28.6%) were resistant to prior immune checkpoint inhibitors (ICIs) and 20 (71.4%) were ICI‑naïve. The overall ORR was 51.8% (14/27 evaluable), including 4 complete responses and 10 partial responses. During a median follow-up of 33.6 months, the median PFS and OS were not reached in the whole population. In ICI‑naïve patients, ORR was 60% with median PFS/OS not reached; in ICI‑resistant patients, ORR was 25% with median PFS of 14.9 months and median OS of 25.4 months. Median time to response was 3.3 months; median DoR was not reached. Grade 3–4 treatment‑related adverse events occurred in 9 patients (32.1%), with no treatment‑related deaths. Exploratory analysis showed that responders had significantly higher baseline LAG‑3⁺ cell density in tumor specimens. Conclusion: Dual LAG‑3/PD‑1 blockade demonstrated promising and durable antitumor activity with manageable safety in both ICI‑naïve and ICI‑resistant advanced ASPS, warranting further investigation.