Efficacy of PD-1/PD-L1 and LAG-3 immune checkpoint inhibitors in the treatment of patients with solid tumor.

Authors

Dahai Hu, Junyi Duan, Piao Xie, Jixing Li, Luyu Zhao, Bin Chen, Rongzhao Lu, Hui Tang, Xiaofei Zheng, Liangzhuo Qu

Published in

Frontiers in immunology. Volume 17. Pages 1809975. Epub Jun 16, 2026.

Abstract

Lymphocyte activation gene 3 (LAG-3) inhibitor, demonstrates limited antitumor efficacy when used alone. Therefore, the clinical efficacy of combining LAG-3 with other immune checkpoint inhibitors warrants further investigation.
The objective of this study is to investigate the efficacy of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and LAG-3 inhibitors in the treatment of patients with solid tumor.
We systematically and independently conducted a literature search using PubMed, Cochrane, and Web of Science, up to December 2025. We selected original studies investigating the efficacy of PD-1/PD-L1 combined with LAG-3 inhibitors in the treatment of solid tumors. Two authors independently extracted trial characteristics and intervention details using a predefined form. Objective response rate (ORR), disease control rate (DCR), median overall survival (OS) or progression-free survival (PFS) with their corresponding 95% confidence intervals (CIs) were used to evaluate the primary outcomes.
A total of six randomized controlled trials were included in the analysis. The results indicated that PD-1/PD-L1 combined with LAG-3 inhibitors significantly improved the DCR (0.66, P < 0.001) and ORR (0.25, P < 0.001) in patients with solid tumors. The median PFS of combination therapy was 3.51 months (P < 0.001). Subgroup analyses revealed that the Chinese population (ORR 0.4, P = 0.001) and individuals aged < 60 years (0.08, P < 0.001) derived greater benefit from PD-1/PD-L1 combined with LAG-3 inhibitor therapy. Additionally, PD-1/PD-L1 combined with LAG-3 inhibitors significantly improved the ORR in patients with nasopharyngeal carcinoma (0.24, P = 0.003).
PD-1/PD-L1 combined with LAG-3 inhibitors demonstrates higher response rates, but the survival outcomes remain unclear. Further, patients with NPC, Chinese population, and individuals aged < 60 years may potentially benefit from the combination therapy.

PMID:
42382737
Bibliographic data and abstract were imported from PubMed on 01 Jul 2026.

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