Multicenter phase 2 trial of first-line cadonilimab plus chemotherapy for PD-L1-negative advanced non-small cell lung cancer

Although immunotherapy is approved for patients with tumors with high PD-L1 expression, optimal therapeutic strategies for PD-L1-negative populations are undefined. A multicenter phase 2 trial in China assessed the safety of cadonilimab (PD-1/CTLA-4 bispecific antibody) plus chemotherapy in patients with PD-L1-negative advanced non-small cell lung cancer (aNSCLC). The primary endpoint, 12-month progression-free survival (PFS) rate, was 42.1% (95% CI 29.6-60.0%), meeting the prespecified threshold. The median overall survival was not reached, the median PFS was 9.7 months, the objective response rate was 66.0%, the disease control rate was 100%, and the median duration of response was 9.5 months. Grade ≥ 3 treatment-related adverse events occurred in 26 patients (52.0%). cfDNA methylation-based molecular response predicted the actual clinical response approximately 5 cycles earlier than conventional radiographic evaluation. The authors conclude that first-line cadonilimab plus chemotherapy showed an encouraging efficacy with manageable safety as first-line treatment for PD-L1-negative aNSCLC.