Abstract Purpose: Prior studies reported synergistic antitumor activity by dual inhibition of lymphocyte activation gene-3 (LAG-3) and PD-1. This study investigated 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 RM-NPC patients received LBL-007 (anti-LAG-3), tislelizumab (anti-PD-1), and gemcitabine-cisplatin for 4 to 6 cycles, followed by maintenance therapy with LBL-007 and tislelizumab. Primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), duration of response (DoR), time to response (TTR), 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, ORR was 83.3% (95% CI, 68.6%-93.0%), and DCR was 97.6% (95% CI, 87.4%-99.9%). Median PFS reached 15.8 months (95% CI, 9.9-not estimable); 12-month PFS rate was 55.1% (95% CI, 41.7%-72.9%). Median DoR was 14.6 months (95% CI, 10.3-not estimable); 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 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.
Sun et al. (2025) studied this question.