CAN-2409 + valacyclovir reports 14.3-month median OS in treated NSCLC patients; 24.5 months in a selected per-protocol group

Aglatimagene besadenovec (CAN-2409) is a replication-defective adenoviral vector encoding HSV-thymidine kinase, designed to trigger immunogenic tumor cell death after exposure to valacyclovir while patients continue an immune checkpoint inhibitor. This open-label, single-arm Phase 2a study in ICI-refractory advanced NSCLC (NCT04495153) enrolled 76 patients (intention-to-treat population); 73 received treatment (safety population). Median OS was 14.3 months in the 73 treated patients and 24.5 months (95% CI 16.0–33.8) in the 46-patient evaluable/per-protocol population, which required two intratumoral injections, protocol-defined valacyclovir exposure, and week-12 imaging. ORR was 10.9% (5/46) and DCR 71.7% (33/46) in that selected evaluable population; among 41 evaluable cohort 2 patients, 37% were alive at ≥24 months and 12% at ≥40 months. No grade 4 treatment-related AEs or treatment-related deaths were reported; grade 3 TRAEs occurred in 13.7% (10/73), and six patients discontinued due to AEs, including two possibly related to treatment or ongoing ICI. Subsequent-line docetaxel±ramucirumab provides historical survival context, but such cross-trial benchmarks cannot establish added benefit for CAN-2409.