ORIGINAL RESEARCH article
Front. Oncol.
Sec. Thoracic Oncology
This article is part of the Research TopicReal-World Data and Real-World Evidence in Lung Cancer Volume IIView all 22 articles
Cadonilimab (PD-1/CTLA-4 bispecific antibody) combination therapy for Driver Gene-Negative Advanced NSCLC: A Single-Center Retrospective Real-World Study
Provisionally accepted
- First Affiliated Hospital, Nanjing Medical University, Nanjing, China
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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.
Keywords: bispecific antibody, Cadonilimab, Driver Gene-Negative, Immunotherapy, Non-small cell lung cancer
Received: 03 Oct 2025; Accepted: 30 Jan 2026.
Copyright: © 2026 Zeng, Xiang, Sun and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kaihua Lu
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