An update on the results of IBI110 (anti-LAG-3 antibody) plus sintilimab (anti-PD-1 antibody) in patients with advanced alveolar soft part sarcoma.

Abstract

11554 Background: At the 2024 ASCO conference, we reported preliminary results on the efficacy and safety of IBI110 (anti-LAG-3 antibody) combined with sintilimab (anti-PD-1 antibody) in advanced alveolar soft part sarcoma (ASPS), which demonstrated an overall response rate (ORR) of 48.1%, including three complete responses (CRs). Here, we provide updated results from this single-arm, phase II trial. Methods: Eligible patients with metastatic or unresectable ASPS were assigned to two cohorts: cohort A (immune checkpoint inhibitor [ICI]-naïve, defined as no prior exposure to anti-PD-1/PD-L1/CTLA-4 antibodies) and cohort B (ICI-failed, defined as imaging-confirmed progression following anti-PD-1/PD-L1 therapy). Patients received IBI110 (200 mg) plus sintilimab (200 mg) intravenously every three weeks (Q3W). Primary endpoints were ORR and progression-free survival (PFS), assessed by investigators per RECIST v1.1, as well as safety. Secondary endpoints included overall survival (OS) and safety profile. Results: A total of 28 patients were enrolled (57.1% male; median age: 30.5 years; ECOG performance status 0: 100%; stage IV: 100%), with 20 patients in cohort A and 8 in cohort B. Responses were evaluable in 27 patients. The ORR was 51.8% across the entire population, including 4 CRs and 8 partial responses (PRs) in cohort A, and 2 PRs in cohort B. As of January 8, 2025, the median follow-up duration was 21.3 months (95% CI: 11.5–29.8). Median PFS and OS were not reached in the overall population (see Table). Treatment-related adverse events (TRAEs) occurred in all patients, with grade ≥3 TRAEs observed in 10 (35.7%) patients. Four TRAEs led to treatment discontinuation, including hemoptysis (n=2), type 1 diabetes mellitus (n=1), and encephalitis (n=1). No TRAE-related deaths were reported. Following discontinuation of LAG-3 antibody production in July 2024, patients achieving CR were advised to discontinue therapy, while those with PR or stable disease (SD) transitioned to sintilimab monotherapy. Notably, no disease progression was observed among these patients, including two who were previously resistant to sintilimab. Tumor microenvironment analysis in 17 patients (10 responders and 7 non-responders) revealed significantly higher LAG-3 density in responders compared to non-responders ( P =0.021). Conclusions: The combination of IBI110 and sintilimab demonstrated promising efficacy in both ICI-naïve and ICI-failed advanced ASPS with an acceptable safety profile. The durable restoration of ICI efficacy persisted despite the discontinuation of combination therapy. LAG-3 expression may serve as a predictive biomarker for response to anti-LAG-3 therapy in ASPS. Survival analysis. Cohort PFS (m) OS (m) A Not reached Not reached B 14.9 25.4 Whole population Not reached Not reached PFS: progression-free survival; OS: overall survival.