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

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; Dongyuan Zhu; Qingshan Li; Xianling Liu; Wuyun Su; Yi Ba; Weiwei Li; Qian Li; Changbin Zhu; Zhan Huang; Xiaoyan Kang; Shilin Xue; Hui Li; Chao Wang; Fan Luo; Yan Huang; Li Zhang; Hongyun Zhao

doi:10.1016/j.xcrm.2025.102396

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

Cell Rep Med. 2025 Oct 21;6(10):102396. doi: 10.1016/j.xcrm.2025.102396. Epub 2025 Oct 3.

Authors

Yuxiang Ma¹, Shaoyan Lin¹, Qun Chen², Jinhui Xue¹, Yunpeng Yang³, Aimin Zang⁴, Ying Cheng⁵, Yiping Zhang⁶, Xiangcai Wang⁷, Zhendong Chen⁸, Song Qu⁹, Jianbo He¹⁰, Chuanben Chen¹¹, Chuan Jin¹², Dongyuan Zhu¹³, Qingshan Li¹⁴, Xianling Liu¹⁵, Wuyun Su¹⁶, Yi Ba¹⁷, Weiwei Li¹⁸, Qian Li¹⁸, Changbin Zhu¹⁸, Zhan Huang¹⁸, Xiaoyan Kang¹⁹, Shilin Xue¹⁹, Hui Li¹⁹, Chao Wang¹⁹, Fan Luo²⁰, Yan Huang²¹, Li Zhang²², Hongyun Zhao²³

Affiliations

¹ Department of Clinical Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, No. 651 Dongfeng East Road, Guangzhou 510060, China.
² Department of Medical Oncology, Fujian Medical University Union Hospital, Fuzhou 350000, China.
³ Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, No. 651 Dongfeng East Road, Guangzhou 510060, China.
⁴ Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding 071000, China.
⁵ Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun 130012, China.
⁶ The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, Zhejiang, China.
⁷ Department of Oncology, First Affiliated Hospital of Gannan Medical University, Ganzhou 341001, China.
⁸ Department of Medical Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230093, China.
⁹ Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Cancer Institute of Guangxi, Nanning 530021, Guangxi, China.
¹⁰ Department of Medical Oncology of Respiratory, Guangxi Medical University Cancer Hospital, Cancer Institute of Guangxi, Nanning 530021, Guangxi, China.
¹¹ Department of Head and Neck Radiation Oncology, Fujian Cancer Hospital, Fuzhou 350000, China.
¹² Department of Medical Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, China.
¹³ Rare Tumors Department, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, China.
¹⁴ Department of Oncology, Affiliated Hospital of Chengde Medical University, Chengde 067000, China.
¹⁵ Department of Oncology, Second Xiangya Hospital, Central South University, Changsha 410011, China.
¹⁶ Department of Medical Oncology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, China.
¹⁷ Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
¹⁸ Department of Translational Medicine, Amoy Diagnostics Co., Ltd, Xiamen 361027, China.
¹⁹ Clinical Research Center, Qilu Pharmaceutical Co., Ltd., Jinan 250000, China.
²⁰ Department of Intensive Care Unit, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, No. 651 Dongfeng East Road, Guangzhou 510060, China.
²¹ Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, No. 651 Dongfeng East Road, Guangzhou 510060, China. Electronic address: huangyan@sysucc.org.cn.
²² Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, No. 651 Dongfeng East Road, Guangzhou 510060, China. Electronic address: zhangli@sysucc.org.cn.
²³ Department of Clinical Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, No. 651 Dongfeng East Road, Guangzhou 510060, China. Electronic address: zhaohy@sysucc.org.cn.

Abstract

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).

Keywords: CTLA-4 antibody; bifunctional PD-1; biomarker; cervical cancer; nasopharyngeal carcinoma; non-small cell lung cancer; phase 1 trial.

Publication types

Clinical Trial, Phase I

MeSH terms

Adult
Aged
Biomarkers, Tumor* / metabolism
CTLA-4 Antigen* / antagonists & inhibitors
CTLA-4 Antigen* / metabolism
Carcinoma, Non-Small-Cell Lung / drug therapy
Female
Humans
Immune Checkpoint Inhibitors* / therapeutic use
Lung Neoplasms / drug therapy
Male
Middle Aged
Nasopharyngeal Carcinoma / drug therapy
Nasopharyngeal Neoplasms / drug therapy
Neoplasms* / drug therapy
Programmed Cell Death 1 Receptor* / antagonists & inhibitors
Programmed Cell Death 1 Receptor* / metabolism
Progression-Free Survival
Treatment Outcome
Uterine Cervical Neoplasms / drug therapy

Substances

Programmed Cell Death 1 Receptor
Biomarkers, Tumor
CTLA-4 Antigen
PDCD1 protein, human
Immune Checkpoint Inhibitors
CTLA4 protein, human

Associated data

ClinicalTrials.gov/NCT05171790
ClinicalTrials.gov/NCT04296994