The efficacy and safety of a novel PD-1/CTLA-4 bispecific antibody cadonilimab (AK104) in advanced non-small cell lung cancer: A multicenter retrospective observational study.

Background: For patients with advanced non-small cell lung cancer (NSCLC) who have received frontline immunochemotherapy, subsequent treatment options are limited. As the first dual programmed cell death-1 (PD-1)/cytotoxic T lymphocyte-associated antigen-4 bispecific antibody approved globally, cadonilimab demonstrated potential antitumor activity in advanced NSCLC patients resistant to anti-PD-1/PD-L1 antibodies.

Methods: We retrospectively collected efficacy and safety data from advanced NSCLC patients treated with cadonilimab-based regimens in later therapy lines.

Results: A total of 41 advanced NSCLC patients refractory to anti-PD-1/PD-L1 therapy were enrolled. More than half of the patients received cadonilimab-based regimen as a fourth or later line of treatment. At the data cutoff date, treatment efficacy could be evaluated in 23 patients. One patient (4.3%) achieved partial response, eight patients (34.8%) experienced stable disease, and 14 patients (60.9%) progressed. The objective response rate and disease control rate were 4.3% and 39.1%, respectively. The median progression-free survival for all evaluated patients was 108.0 days. Due to the short follow-up period, the median overall survival has not yet been reached. Treatment-related adverse events (TRAEs) and immune-related AEs occurred in 63.4% and 22% patients, respectively. The most common TRAEs included gamma-glutamyl transferase elevation (17.1%), coughing (14.6%), and fatigue (12.2%). Five patients (12.2%) experienced grade ≥3 TRAEs.

Conclusions: In this heavily pretreated cohort of advanced NSCLC patients, cadonilimab-based regimens showed moderate antitumor efficacy with a generally tolerable and manageable safety profile. However, more evidence is needed to support the administration of cadonilimab in NSCLC patients refractory to previous anti-PD-1/PD-L1 therapy.