Efficacy and safety of anti-LAG-3 IBI110 in combination with sintilimab and chemotherapy for advanced squamous non-small cell lung cancer: a randomized phase II study
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: OBJECTIVE: To evaluate the efficacy and safety of the anti-lymphocyte activation gene-3 (LAG-3) antibody IBI110 in combination with sintilimab and chemotherapy in patients with advanced squamous non-small cell lung cancer (sqNSCLC). METHODS: In this multicenter, randomized, open-label, phase II study, 153 patients with previously untreated advanced sqNSCLC were randomly assigned at a 1:1:1 ratio to one of three groups: IBI110 200 mg plus sintilimab (200 mg) and chemotherapy (n = 51), IBI110 600 mg plus sintilimab and chemotherapy (n = 51), or sintilimab plus chemotherapy (standard-of-care, SOC, n = 51). The primary endpoints included the objective response rate (ORR), progression-free survival (PFS) and safety. LAG-3 expression in tumor tissue was detected by immunohistochemistry (IHC) to explore its correlation with treatment efficacy. RESULTS: While no statistically significant differences in ORR, PFS, or overall survival (OS) were observed across the three arms in the overall population, promising efficacy signals emerged in the LAG-3 expression ≥ 2% subgroup. In this subset, compared with the SOC regimen, the IBI110 200 mg regimen significantly improved the duration of response (DOR: 13.73 vs. 6.51 months, P = 0.037) and PFS (P = 0.0485). The safety results indicated that the IBI110 200 mg combination was manageable, with a higher incidence of grade ≥ 3 treatment-related adverse events (56.86% vs. 29.41%) primarily consisting of controllable hematological toxicities. CONCLUSION: The high-LAG-3 subgroup demonstrated enhanced efficacy following the addition of IBI110 to sintilimab and chemotherapy, despite the absence of improvement in the overall population with advanced sqNSCLC, supporting further investigations in biomarker-defined patients. TRIAL REGISTRATION: The current study has been registered with ClinicalTrial.gov (Identifier: NCT04085185).
Source: Cancer Immunology Immunotherapy
Institutions: Tongji University, Shanghai East Hospital, First Affiliated Hospital Zhejiang University, Zhejiang University, Hunan Cancer Hospital, First Hospital of Jilin University, Peking University Cancer Hospital, Fujian Provincial Cancer Hospital, Wuhan Union Hospital, Huazhong University of Science and Technology, First Affiliated Hospital of Nanchang University, Second Affiliated Hospital of Guangzhou Medical University, Henan University of Science and Technology, First Affiliated Hospital of Henan University of Science and Technology, Third Hospital of Changsha, Capital Medical University, Beijing Chest Hospital, Chongqing University, Chongqing Cancer Hospital, Mianyang Central Hospital, Xiangyang Central Hospital, Innovent Biologics (China)
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,590
Funder: Innovent Biologics
OpenAlex ID: W7125792432