Phase 2 trial of dual inhibition of LAG-3 and PD-1 with IBI110 and sintilimab in advanced alveolar soft part sarcoma

Current standard therapy with PD-(L)1 inhibitors for alveolar soft part sarcoma (ASPS) achieves limited response rates (<40%). LAG-3 is coexpressed with PD-1 on exhausted T cells. A phase 2 trial at Peking University Cancer Hospital and Institute (Beijing, China) evaluated the combination of IBI110 (anti-LAG-3) and sintilimab (anti-PD-1) for advanced ASPS. The trial included patients who received both drugs at 200 mg every 3 weeks. The primary endpoint was overall response rate (ORR). Among 28 patients, 8 (28.6%) were resistant to prior immune checkpoint inhibitors (ICI) and 20 (71.4%) were ICI-naïve. The ORR among 27 evaluable patients was 51.8%, including 4 complete responses and 10 partial responses. Median progession-free survival (PFS) and overall survival (OS) were not reached during a median follow-up of 33.6 months. Among ICI-naïve patients, the ORR was 60%, with median PFS and OS not reached. Among ICI-resistant patients, the ORR was 25%, with median PFS 14.9 months and median OS 25.4 months. The median time to response was 3.3 months; the median duration of response was not reached. Grade 3 or 4 treatment-related adverse events occurred in nine patiens (32.1%), with no treatment-related deaths. Exploratory analysis showed that responders had significantly higher baseline LAG-3⁺ cell density in tumor specimens. The authors conclude that dual LAG-3/PD-1 blockade demonstrated promising and durable antitumor efficacy with manageable safety in both ICI-naïve and ICI-resistant advanced ASPS.