biostudies-literatureZeng LNational Natural Science Foundation of China (National Science Foundation of China)567https://www.ebi.ac.uk/biostudies/studies/S-EPMC12808239biostudies-literatureUnknown17(1)Immune checkpoint inhibitors (ICIs) have improved survival in advanced non-small cell lung cancer (NSCLC), yet resistance remains a major challenge. Here, we report the results from cohort A of a multi-cohort, phase II, open-label trial [NCT04777084], evaluating the efficacy and safety of IBI318 (a bispecific anti-PD-1/PD-L1 antibody, 300 mg intravenous every 2 weeks) plus lenvatinib (a receptor tyrosine kinase inhibitor, 8 mg orally daily). Forty patients with advanced NSCLC and acquired resistance to first-line ICIs were enrolled and received at least 1 cycle of the study regimen. The primary endpoint of 12-week objective response rate was 40.0% (95% CI: 24.9-56.7), satisfying prespecified efficacy threshold. Secondary endpoints included other efficacy endpoints and safety. Median progreNature communicationsPD-1/ PD-L1 bispecific antibody IBI318 combined with lenvatinib in advanced non-small cell lung cancer with acquired resistance to immune checkpoint inhibitors: a phase II trial.PMC128082398217333882222048Zhang GRuan ZLiu LDeng JDeng LFang CZou CWang JSong LXiong YJiang WZhou CWei SChen YChen XChen SWang ZZhou HYang HZeng LYang NXu QZeng ZYang DSun YLi YHuang ZLi TZhang YZhang XQin HXu SZeng FYan HDai JfalsePD-1/ PD-L1 bispecific antibody IBI318 combined with lenvatinib in advanced non-small cell lung cancer with acquired resistance to immune checkpoint inhibitors: a phase II trial.Immune checkpoint inhibitors (ICIs) have improved survival in advanced non-small cell lung cancer (NSCLC), yet resistance remains a major challenge. Here, we report the results from cohort A of a multi-cohort, phase II, open-label trial [NCT04777084], evaluating the efficacy and safety of IBI318 (a bispecific anti-PD-1/PD-L1 antibody, 300 mg intravenous every 2 weeks) plus lenvatinib (a receptor tyrosine kinase inhibitor, 8 mg orally daily). Forty patients with advanced NSCLC and acquired resistance to first-line ICIs were enrolled and received at least 1 cycle of the study regimen. The primary endpoint of 12-week objective response rate was 40.0% (95% CI: 24.9-56.7), satisfying prespecified efficacy threshold. Secondary endpoints included other efficacy endpoints and safety. Median progre2025-01-01T00:00:00Z2025 Dec2026-07-15T11:17:35.328Z2026-07-04T03:12:16.575ZS-EPMC128082394139816210.1038/s41467-025-67262-x