This study evaluated the safety and preliminary efficacy of SBRT combined with cadonilimab in patients with refractory solid tumors who had failed multiple lines of prior therapy. The results demonstrated favorable tolerability and durable anti-tumor effects, providing critical evidence for future investigations.
Literature Overview
This article titled 'Stereotactic body radiotherapy plus cadonilimab (PD-1/CTLA-4 bispecific antibody) as third-line or beyond therapy for refractory solid tumors: A phase 1b study' published in Cancer Communications reviews novel therapeutic strategies for refractory solid tumors.
Background Knowledge
Solid tumors often develop resistance or recurrence after multiple systemic treatments, presenting significant clinical challenges. While immune checkpoint inhibitors (ICIs) have shown durable anti-tumor responses in various cancers, monotherapy yields limited efficacy in refractory cases. Cadonilimab, a bispecific antibody targeting both PD-1 and CTLA-4, demonstrates improved safety compared to traditional ICI combination regimens. Stereotactic body radiotherapy (SBRT) enhances anti-tumor immune activation through high-precision, high-dose radiation delivery, with existing studies confirming synergistic effects when combined with ICIs. This combination may offer new therapeutic opportunities for patients with refractory solid tumors who have exhausted multiple treatment lines.
Research Methods and Experiments
This single-arm, open-label phase 1b trial enrolled 63 advanced solid tumor patients who had received at least two prior treatment lines. Participants underwent SBRT combined with intravenous cadonilimab (6 mg/kg every two weeks). Primary endpoint was safety, with secondary endpoints including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Survival data were analyzed using Kaplan-Meier and Cox regression methods, with tumor responses evaluated per RECIST v1.1 criteria.
Key Conclusions and Perspectives
Research Significance and Prospects
This study provides initial evidence supporting the safety and anti-tumor activity of SBRT plus cadonilimab in refractory solid tumors, establishing foundation for future multicenter randomized controlled trials. Further investigations should explore efficacy differences across tumor subtypes and optimize treatment sequencing and dose intensity to enhance immune activation.
Conclusion
This first-in-clinic evaluation of SBRT combined with cadonilimab for refractory solid tumors demonstrates favorable safety profiles in heavily pretreated patients, with notable advantages in local control and survival outcomes. The identification of ECOG PS scores and treatment cycle numbers as independent predictive factors suggests early and sustained therapy may improve efficacy. While limited by single-arm design and small sample size, these findings establish critical groundwork for large-scale randomized controlled trials and open new research avenues for combination immuno-radiotherapy approaches in refractory cancers.
