Anti-PD-1/CTLA-4 bispecific antibody-based combination therapy for cervical cancer: a multicenter study with...

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.

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.

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.

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.