Abstract
PURPOSE: Prior studies reported synergistic antitumor activity by dual inhibition of lymphocyte activation gene-3 (LAG-3) and PD-1. This study investigated the activity, safety, and biomarker of LAG-3/PD-1 co-blockade plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). PATIENTS AND METHODS: Previously untreated patients with RM-NPC received LBL-007 (anti-LAG-3), tislelizumab (anti-PD-1), and gemcitabine-cisplatin for four to six cycles, followed by maintenance therapy with LBL-007 and tislelizumab. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), duration of response (DoR), time to response, disease control rate (DCR), overall survival (OS), and safety. Biomarker analysis included LAG-3 and PD-L1 expression. RESULTS: Forty-two patients were enrolled from 15 centers in China. With a median follow-up of 19.0 months, the ORR was 83.3% [95% confidence interval (CI), 68.6%-93.0%], and the DCR was 97.6% (95% CI, 87.4%-99.9%). The median PFS reached 15.8 months (95% CI, 9.9-not estimable); the 12-month PFS rate was 55.1% (95% CI, 41.7%-72.9%). The median DoR was 14.6 months (95% CI, 10.3-not estimable); the median OS was not reached. Grade 3 or higher treatment-related adverse events occurred in 37 patients (98.1%). No new safety signals were identified. In biomarker analysis, patients with dual-positive LAG-3/PD-L1 expression demonstrated more favorable outcomes than those lacking either biomarker, including a 12-month PFS rate of 65.0% versus 40.2% and median PFS of 16.0 versus 10.3 months. CONCLUSIONS: LBL-007 plus tislelizumab and chemotherapy shows promising clinical benefits and manageable toxicity as first-line therapy for RM-NPC. Dual-positive LAG-3/PD-L1 expression was associated with improved outcomes, supporting further exploration of this biomarker-defined subpopulation in randomized trials.