Anti‐PD‐1/CTLA‐4 bispecific antibody‐based combination therapy for cervical cancer: a multicenter study with biomarker analysis
4 affiliations
- 1Department of Oncology, The Second Xiangya Hospital, Central South University , ,
- 2Department of Gynecologic Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University , ,
- 3Department of Oncology, Changde Hospital, Xiangya School of Medicine , ,
- 4Department of General Surgery, The Second Xiangya Hospital, Central South University , ,
Abstract
Background: Cadonilimab is a PD‐1/CTLA‐4 bispecific antibody with robust activity in platinum‐pretreated advanced cervical cancer, while its first‐line value and resistance mechanisms remain unclear.
Methods: This multicenter retrospective study enrolled 52 treatment‐naive patients with recurrent/metastatic cervical cancer (R/M CC) receiving cadonilimab plus chemotherapy. We assessed clinical efficacy and safety, and performed RNA‐seq and immunohistochemistry for exploratory biomarker analysis.
Results: The 2‐year overall survival, 2‐year progression‐free survival and objective response rate were 82.6%, 66.7% and 75.0%, respectively. Main treatment‐related adverse events included myelosuppression, thyroid dysfunction, gastrointestinal reactions and fatigue, demonstrating acceptable safety. Transcriptomic data showed suppressed Hippo, NF‐κB, RIG‐1 pathways and reduced M1‐macrophage polarization in patients with longer PFS. Candidate genes including GGT6 and FRG2 were identified as putative resistance‐associated markers in this small exploratory cohort. Higher M1‐macrophage polarization and p‐STAT1 expression were observed in short‐PFS patients, indicating a possible link between p‐STAT1 activation and M1‐macrophage enrichment. Of note, outcomes should be interpreted considering the retrospective single‐arm design and limited sample size.
Conclusions: Cadonilimab‐containing regimen achieved promising efficacy and an acceptable safety profile as first‐line therapy for R/M CC. The biomarker findings are exploratory and provide preliminary evidence for future research on bispecific‐antibody resistance.
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BibTeX
@article{li2026antipd1ctla4,
title = {{Anti‐PD‐1/CTLA‐4 bispecific antibody‐based combination therapy for cervical cancer: a multicenter study with biomarker analysis}},
author = {Jiwei Li and Yuping Deng and Tao Wu and Chao Xu and Wen Zou and Jia Yao and Jingjing Wang},
journal = {Frontiers in immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1967065},
url = {https://europepmc.org/article/PMC/PMC13669150},
note = {CC BY},
}
RIS
TY - JOUR
TI - Anti‐PD‐1/CTLA‐4 bispecific antibody‐based combination therapy for cervical cancer: a multicenter study with biomarker analysis
AU - Jiwei Li
AU - Yuping Deng
AU - Tao Wu
AU - Chao Xu
AU - Wen Zou
AU - Jia Yao
AU - Jingjing Wang
PY - 2026
DA - 2026/10/01
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1967065
UR - https://europepmc.org/article/PMC/PMC13669150
AB - Background: Cadonilimab is a PD‐1/CTLA‐4 bispecific antibody with robust activity in platinum‐pretreated advanced cervical cancer, while its first‐line value and resistance mechanisms remain unclear. Methods: This multicenter retrospective study enrolled 52 treatment‐naive patients with recurrent/metastatic cervical cancer (R/M CC) receiving cadonilimab plus chemotherapy. We assessed clinical efficacy and safety, and performed RNA‐seq and immunohistochemistry for exploratory biomarker analysis. Results: The 2‐year overall survival, 2‐year progression‐free survival and objective response rate were 82.6%, 66.7% and 75.0%, respectively. Main treatment‐related adverse events included myelosuppression, thyroid dysfunction, gastrointestinal reactions and fatigue, demonstrating acceptable safety. Transcriptomic data showed suppressed Hippo, NF‐κB, RIG‐1 pathways and reduced M1‐macrophage polarization in patients with longer PFS. Candidate genes including GGT6 and FRG2 were identified as putative resistance‐associated markers in this small exploratory cohort. Higher M1‐macrophage polarization and p‐STAT1 expression were observed in short‐PFS patients, indicating a possible link between p‐STAT1 activation and M1‐macrophage enrichment. Of note, outcomes should be interpreted considering the retrospective single‐arm design and limited sample size. Conclusions: Cadonilimab‐containing regimen achieved promising efficacy and an acceptable safety profile as first‐line therapy for R/M CC. The biomarker findings are exploratory and provide preliminary evidence for future research on bispecific‐antibody resistance.
SN - 1664-3224
ER -