Aggarwal, Charu; Sterman, Daniel; Dwyer, Jessica; Alesi, Erin R.; Maldonado, Fabien; Mehra, Ranee; Bestvina, Christine; Reisenauer, Janani; Patel, Shiven; Ibrahim, Omar; Eapen, George; Guesdon, William; Chung, Matthew Wai Heng; Duault, Caroline; Pichavant, Mina Rohani; Gnjatic, Sacha; Kim-Schulze, Seunghee; Maecker, Holden T.; Diers, Anne R.; Guo, Qiuchen; Nichols, Garrett; Manzanera, Andrea; Barone, Francesca; Tak, Paul P. (2026).听.听Journal for ImmunoTherapy of Cancer, 14(9).听
Patients with advanced non-small cell lung cancer whose disease progresses despite immune checkpoint inhibitor therapy have limited treatment options. This phase 2a study evaluated CAN-2409, a gene therapy injected directly into tumors, combined with the antiviral drug valacyclovir and ongoing immunotherapy. Among 73 patients who received treatment, median overall survival was 14.3 months. Among 46 patients who completed the protocol-defined treatment and 12-week imaging, median survival was 24.5 months, 10.9% had tumor shrinkage meeting response criteria, and 71.7% achieved disease control. Exploratory analyses also found signs of immune activation and regression of some tumors that were not directly injected. Most treatment-related side effects were mild to moderate, although 13.7% of treated patients experienced severe (grade 3) events; no grade 4 treatment-related events or treatment-related deaths were reported. These findings suggest potentially encouraging activity, but because this was a single-arm study and the results may be affected by patient selection and other biases, the treatment鈥檚 effectiveness must be confirmed in a randomized clinical trial.
Figure 1
Patient survival in evaluable (per-protocol) and safety populations. (a) Kaplan-Meier curve representing overall survival in months (from date of first injection) for evaluable patients in cohorts 1 and 2 (n=46). (b) Kaplan-Meier curve for overall survival analysis in months for all evaluable patients in cohort 2 (n=41). (c) Table of number of cohort 2 patients alive at different timepoints, illustrating the long tail of survival. (d) Kaplan-Meier curve for overall survival analysis for cohort 2 evaluable patients (n=41) by baseline PD-L1 status of <1% (negative) and >1% (positive).