Treatment with the viral immunotherapy CAN-2409 helped patients with unresectable, stage III/IV non–small cell lung cancer (NSCLC) continue on immune checkpoint inhibition longer and experience extended survival, despite initial inadequate responses to anti–PD-(L)1 therapy, according to extended follow-up results from a phase IIa study presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC; Abstract MA10.02).
“This extended follow-up confirms the durable survival benefit of CAN-2409 for patients who otherwise have limited treatment options after [failure of] ICI therapy,” stated presenting investigator Charu Aggarwal, MD, MPH, FASCO, Leslye Heisler Professor for Lung Cancer Excellence, and Section Chief of Thoracic and Head and Neck Cancer, Division of Hematology-Oncology, Perelman School of Medicine, University of Pennsylvania. “These results strongly support advancing CAN-2409 into a larger, randomized controlled trial, particularly in patients with nonsquamous histology.”
Background and Study Methods
CAN-2409 is a replication-defective adenovirus that encodes the HSV-tk gene. The open-label phase IIa trial looked at the use of CAN-2409 plus valacyclovir in combination with continued immune checkpoint inhibition in patients with unresectable, stage III/IV NSCLC who were refractory or resistant to anti–PD-(L)1 therapy. Participants were enrolled into one of two cohorts according to their disease status at enrollment: patients with stable disease went into cohort 1 and those with progressive disease were in cohort 2.
In the study, patients received two doses of CAN-2409 (5 x 1011 vp) that were injected 5 to 7 weeks apart through bronchoscopic or percutaneous injections, and the oral prodrug valacyclovir was administered for 15 days.
Prior results from the study were presented at the 2024 ASCO Annual Meeting, showing encouraging overall survival in the overall patient population.
Patient follow-up continued through 32.4 months, and the investigators looked at extended follow-up and explorative predictive biomarker results.
Key Study Findings
Forty-six of 76 patients were evaluable for extended follow-up results. The median overall survival in the overall population from both cohorts was 24.5 months.
In the second cohort specifically, the median overall survival was 21.5 months; 37% of patients were still alive more than 2 years after treatment. At least 40 months from treatment, the survival rate was 12%, and 5% after more than 50 months.
“Notably, patients with nonsquamous histology demonstrated longer overall survival than those with squamous histology (25.4 vs 13.3 months), linked to a significant increase in cytotoxic effector T cells and other favorable immunological changes following treatment,” said Dr. Aggarwal. In those with nonsquamous histology, more significant changes in circulating T cells, B cells, and dendritic cells were observed after injection with CAN-2409.
Abscopal responses were also noted with shrinkage of uninjected sited in 69% of patients with multiple lesions.
The favorable safety and tolerability profile of CAN-2409 continued through extended follow-up.
The study authors noted that the findings support the initiation of a larger, randomized, controlled trial of CAN-2409 in patients with advanced NSCLC and nonsquamous histology after progression on immune checkpoint inhibition.
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