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

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. 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. 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. 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.