Updated efficacy and predictive biomarkers of QL1706, a bifunctional PD-1/CTLA-4 dual blocker in advanced solid tumors—A phase 1/1b study

作者：Yuxiang Ma, Shaoyan Lin, Qun Chen, Jinhui Xue, Yunpeng Yang, Aimin Zang, Ying Cheng, Yiping Zhang, Xiangcai Wang, Zhendong Chen, Song Qu, Jianbo He, Chuanben Chen, Chuan Jin, Dong Zhu, Qingshan Li, Xianling Liu, Wuyun Su, Yi Ba, Weiwei Li, Qian Li, Changbin Zhu, Zhan Huang, Xiaoyan Kang, Shilin Xue, Huijun Li, Chao Wang, Fan Luo, Yan Huang, Li Zhang, Hongyun Zhao · 发表于：Cell Reports Medicine · 年份：2025 · DOI：10.1016/j.xcrm.2025.102396 · 研究领域：Cancer Immunotherapy and Biomarkers、Cancer, Stress, Anesthesia, and Immune Response、Cancer Cells and Metastasis

QL1706 has shown promising efficacy in solid tumors in a phase 1/1b study. Here, we report updated long-term survival outcomes and biomarker analyses. Among 468 patients treated with QL1706 (5 mg/kg), median progression-free survival (mPFS) and overall survival (mOS) are 1.5 and 14.2 months for non-small cell lung cancer (NSCLC), 1.9 and 20.2 months for nasopharyngeal carcinoma (NPC), and 4.2 and 18.6 months for cervical cancer (CC), respectively. Liver metastasis is correlated with poor progression-free survival (PFS) and overall survival (OS) in NSCLC and poor OS in CC, while elevated lactate dehydrogenase is linked to shorter PFS and OS in NPC. CDK4/11q13 diploid or the expression of GZMK high & MYC low distinguishes NPCs with the most favorable PFS. In NSCLC, PD-L1 + /TIL + or a low ARG1:CXCL13 ratio indicates better outcomes. QL1706 offers long-term survival benefits in solid tumors, with identified molecular markers aiding in selecting suitable candidates. This study has been registered on clinicaltrials.gov (NCT04296994 and NCT05171790).