Cadonilimab (PD-1/CTLA-4 bispecific antibody) combination therapy for driver gene-negative advanced NSCLC: a single-center retrospective real-world study

Objective Immunotherapy has made significant progress in the treatment of advanced non-small cell lung cancer (NSCLC). However, treatment options for driver gene-negative patients remain limited. This study evaluated the efficacy and safety of Cadonilimab (AK104), a bispecific PD-1/CTLA-4 antibody, in this population. Methods We retrospectively analyzed real-world data from driver gene–negative advanced NSCLC patients treated with AK104. Outcomes included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Results Among 30 patients, AK104 combination therapy achieved an ORR of 23.3%, DCR of 80%, and median PFS (mPFS) of 6.3 months. The combination of AK104 with chemotherapy and other anti-angiogenic inhibitors (AAI) achieved a notable mPFS of 11.1 months. First-line treatment (n=12) yielded ORR 50%, DCR 100%, and mPFS 13.3 months; second-line (n=6) ORR 16.7%, DCR 100%, mPFS 7.7 months; beyond second-line (n=12) ORR 0%, DCR 50%, mPFS 2.6 months. No significant difference in mPFS was observed between PD-L1–positive and PD-L1–negative patients (4.5 vs. 3.0 months, P = 0.76). Common adverse events included anemia (66.7%), leukopenia (63.3%), neutropenia (56.7%), and thrombocytopenia (53.3%), with grade 3 events in 16.7%. One patient discontinued due to immune-related pancreatitis, and no deaths occurred. Conclusions This study confirms the promising efficacy and acceptable safety profile of AK104 combination therapy in patients with driver gene-negative advanced NSCLC. These findings collectively support the need for further large-scale prospective studies to validate its clinical utility.