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<p>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 progression-free and overall survival were 6.9 months (95% CI: 4.8–9.5) and 18.2 months (95% CI: 10.7–29.1), respectively. The most common treatment-related adverse event was increased thyroid-stimulating hormone (n = 11). Grade ≥3 adverse events occurred in 12.5% (5/40) of patients. Further, we performed a post-hoc exploratory analysis and developed an XGBoost model (scPro-X) using scRNA-seq data from pre-treatment tumor samples&#xa0;to predict 12-week ORR identified CD4_Tfh_CXCL13 and CD8_Tex_CTLA4 as potential biomarkers predictive of response. These findings demonstrate that IBI318 plus lenvatinib exhibit promising clinical activity and a manageable safety profile in patients with advanced NSCLC.</p>

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PD-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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月15日

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  • Liang Zeng,
  • Zhaohui Ruan,
  • Huan Yan,
  • Haoyue Qin,
  • Zhen Zeng,
  • Chun Zou,
  • Zhe Huang,
  • Wenjuan Jiang,
  • Jiacheng Dai,
  • Shidong Xu,
  • Lianxi Song,
  • Yangqian Chen,
  • Yuda Zhang,
  • Fanxu Zeng,
  • Shiyou Wei,
  • Shanmei Chen,
  • Li Liu,
  • Yi Xiong,
  • Zhan Wang,
  • Jun Deng,
  • Xing Zhang,
  • Yuanze Sun,
  • Dan Yang,
  • Chunhua Zhou,
  • Haiyan Yang,
  • Yizhi Li,
  • Li Deng,
  • Qinqin Xu,
  • Chao Fang,
  • Xue Chen,
  • Jing Wang,
  • Ting Li,
  • Gao Zhang,
  • Hui Zhou,
  • Nong Yang,
  • Yongchang Zhang

摘要

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 progression-free and overall survival were 6.9 months (95% CI: 4.8–9.5) and 18.2 months (95% CI: 10.7–29.1), respectively. The most common treatment-related adverse event was increased thyroid-stimulating hormone (n = 11). Grade ≥3 adverse events occurred in 12.5% (5/40) of patients. Further, we performed a post-hoc exploratory analysis and developed an XGBoost model (scPro-X) using scRNA-seq data from pre-treatment tumor samples to predict 12-week ORR identified CD4_Tfh_CXCL13 and CD8_Tex_CTLA4 as potential biomarkers predictive of response. These findings demonstrate that IBI318 plus lenvatinib exhibit promising clinical activity and a manageable safety profile in patients with advanced NSCLC.