Anti-LAG-3 antibody LBL-007 plus anti-PD-1 antibody toripalimab in advanced nasopharyngeal carcinoma and other solid tumors: an open-label, multicenter, phase Ib/II trial

• Published in: Journal of hematology and oncology Vol. 18; no. 1; pp. 15 - 10
• Main Authors: Chen, Gang, Sun, Dong-Chen, Ba, Yi, Zhang, Ya-Xiong, Zhou, Ting, Zhao, Yuan-Yuan, Zhao, Hong-Yun, Fang, Wen-Feng, Huang, Yan, Wang, Zhen, Deng, Chao, Hu, De-Sheng, Wang, Wei, Lin, Jin-Guan, Li, Gui-Ling, Luo, Su-Xia, Fu, Zhi-Chao, Zhu, Hai-Sheng, Wang, Hui-Li, Cai, Sheng-Li, Kang, Xiao-Qiang, Zhang, Li, Yang, Yun-Peng
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 07.02.2025; BioMed Central; BMC
• Subjects: Adult; Adverse events; Aged; Alanine transaminase; Antibodies; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antigens, CD - immunology; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antitumor activity; Aspartate; Aspartate aminotransferase; Biomarkers; Cancer; Carcinoma; CD223 antigen; Combination therapy; Consent; Disease control; Esophageal cancer; FDA approval; Female; Humans; Hyponatremia; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Lung cancer; Lymphocyte Activation Gene 3 Protein; Lymphocytes; Male; Medical research; Medicine, Experimental; Melanoma; Middle Aged; Nasopharyngeal carcinoma; Nasopharyngeal Carcinoma - drug therapy; Nasopharyngeal Carcinoma - pathology; Nasopharyngeal Neoplasms - drug therapy; Neoplasms - drug therapy; Patients; PD-1 protein; PD-L1 protein; Product development; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Solid tumors; Squamous cell carcinoma; Toxicity; Tumors; Viral antibodies
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-025-01666-6

Open-label phase Ib/II study to investigate the safety and efficacy of LBL-007, an anti-LAG-3 antibody, plus toripalimab, an anti-PD-1 antibody, in patients with previously treated advanced nasopharyngeal carcinoma (NPC) and other solid tumors. Patients with advanced tumors refractory to prior standard therapies were enrolled. In phase Ib, patients received LBL-007 200 mg or 400 mg and toripalimab 240 mg intravenously once every 3 weeks. In phase II, all patients received LBL-007 at the recommended phase II dose (RP2D) and toripalimab 240 mg intravenously once every 3 weeks. The primary end points were safety in phase Ib and objective response rate (ORR) in phase II. The exploratory end point was the predictive capability of LAG-3 and PD-L1 expression for efficacy. Between November 30, 2021, and December 1, 2023, 80 patients were enrolled, including 30 (37.5%) with NPC and 50 (62.5%) with other tumors. Median follow-up was 26.0 months. In Phase Ib, LBL-007 was administered at 200 mg to four patients and 400 mg to six patients, with no dose-limiting toxicities observed. Therefore, the 400 mg dose of LBL-007 was established as the RP2D and administered to 70 patients in phase II. Nine (11.3%) of 80 patients had grade 3 or 4 treatment-related adverse events, the most common of which included anemia (2.5%), hyponatremia (2.5%), increased alanine aminotransferase (2.5%), increased aspartate aminotransferase (1.3%), and fatigue (1.3%). Eight patients (10.0%) had treatment-related serious adverse events. No treatment-related deaths were reported. In immunotherapy-naive NPC patients (n = 12), ORR was 33.3%, disease control rate (DCR) was 75%, and median progression-free survival (PFS) was 10.8 months (95% CI, 1.3 to not estimated). In IO-treated NPC patients (n = 17), ORR was 11.8%, DCR was 64.7%, and median PFS was 2.7 months (95% CI, 1.4 to 4.9). For other tumors, ORRs were 15.8% in immunotherapy-naive patients and 3.7% in immunotherapy-treated patients. Patients with ≥ 2 + LAG-3 expression had a higher ORR of 28.0%, compared to 7.7% in those with < 2 + LAG-3 expression. LBL-007 plus toripalimab exhibited a manageable safety profile in patients with advanced solid tumors and demonstrated promising antitumor activity in NPC, especially in immunotherapy-naive patients. These findings warrant further validation in future studies.