Candel Therapeutics reports 24.5-month median overall survival with aglatimagene besadenovec plus valacyclovir in Phase 2a NSCLC study.
Written By: Malavatu Satvika, PharmD
Reviewed By: Pharmacally Editorial Team
Candel Therapeutics has announced publication of final Phase 2a clinical trial results evaluating aglatimagene besadenovec plus valacyclovir in patients with unresectable stage III/IV non-small cell lung cancer (NSCLC) who had an inadequate response to immune checkpoint inhibitor (ICI) therapy. Published in the Journal for ImmunoTherapy of Cancer, the findings reported a median overall survival (OS) of 24.5 months in the evaluable population, along with evidence of systemic immune activation. The clinical trial was registered as NCT04495153.
Phase 2a Study Evaluated Patients with Limited Treatment Options
The open-label Phase 2a study enrolled 76 patients, of whom 73 received at least one dose of aglatimagene besadenovec and comprised the safety population. The evaluable population included 46 patients who received two intratumoral injections of aglatimagene besadenovec, completed protocol-defined valacyclovir exposure, and underwent imaging at Week 12. Patients continued ICI therapy during the study.
Aglatimagene besadenovec, also known as CAN-2409, is a replication-defective adenoviral vector encoding the herpes simplex virus thymidine kinase (HSV-tk) gene. Administered directly into accessible tumors, the investigational therapy is designed to work with valacyclovir to induce immunogenic tumor cell death and promote an anti-tumor immune response. This approach is intended to generate immune activity that can extend beyond the directly injected lesions to uninjected tumors.
24.5-Month Median Overall Survival in the Evaluable Population
The study reported a median OS of 24.5 months in the 46-patient evaluable population, with a 95% confidence interval of 16.0 to 33.8 months. In the broader safety population of 73 patients who received at least one treatment dose, median OS was 14.3 months.
Among the 41 evaluable patients in cohort 2, who had progressive disease at baseline despite previous ICI treatment, 15 patients (37%) remained alive for at least 24 months and five patients (12%) remained alive for at least 40 months.
The objective response rate was 10.9% (5/46), while the disease control rate was 71.7% (33/46) in the evaluable population. Because the study was single-arm, these findings should be interpreted as descriptive rather than as evidence of comparative efficacy.
Treatment Showed Evidence of Systemic Immune Activation
The study also provided evidence that treatment could generate an immune response beyond the injected tumor lesions. Exploratory biomarker analyses showed expansion of cytotoxic T cells and regression of uninjected lesions, supporting systemic immune activation. Among patients with more than one evaluable lesion, reduction of uninjected lesions was observed in 69% of patients, providing clinical evidence consistent with a systemic or abscopal response.
The investigators also reported increased cytotoxic T-cell activity in tumor tissue and expansion of activated CD8-positive effector and central-memory T cells in peripheral blood, with immune changes most evident following the second treatment administration.
Safety Findings Were Generally Consistent with the Treatment
Aglatimagene besadenovec plus valacyclovir was generally well tolerated in the Phase 2a study. Most treatment-related adverse events were Grade 1 or 2. Ten of 73 patients (13.7%) experienced Grade 3 treatment-related adverse events, while no Grade 4 treatment-related adverse events or treatment-related deaths were reported. Six patients discontinued treatment because of adverse events, including two events considered possibly related to treatment.
Findings Support Further Randomized Evaluation
The Phase 2a results provide clinical and immunological findings supporting further evaluation of aglatimagene besadenovec plus valacyclovir in advanced NSCLC. However, the study was single-arm, and comparisons with historical treatment outcomes can be affected by selection and other biases. The investigators therefore concluded that the efficacy findings require confirmation in a randomized controlled trial.
Candel has initiated the global Phase 3 AURORA trial (NCT07660094), a randomized, open-label study evaluating aglatimagene besadenovec plus valacyclovir with continued pembrolizumab versus standard-of-care docetaxel in patients with metastatic stage IV non-squamous NSCLC whose disease has progressed despite prior pembrolizumab and platinum-based chemotherapy. The trial is expected to enroll patients across approximately 150 sites, with overall survival as its primary endpoint.
The randomized AURORA study will provide an important test of whether the survival and systemic immune activity observed in the Phase 2a study can be reproduced against standard chemotherapy in a controlled clinical setting.
Reference
Candel Therapeutics Announces Publication of Phase 2a Trial Data that Demonstrated Prolonged Survival after Systemic Immune Reactivation by Aglatimagene Besadenovec plus Valacyclovir in Patients with Unresectable Stage III/IV NSCLC with an Inadequate Response to ICI, Candel Therapeutics, 01 October 2026
Aggarwal C, Sterman D, Dwyer J, Alesi ER, Maldonado F, Mehra R, et al. Prolonged survival after systemic immune reactivation by aglatimagene besadenovec plus valacyclovir in patients with unresectable stage III/IV NSCLC with an inadequate response to ICI. Journal for ImmunoTherapy of Cancer. 2026;14:e015821. https://doi.org/10.1136/jitc-2026-015821
CAN-2409 Plus Prodrug with Standard of Care Immune Checkpoint Inhibitor for Stage III/IV NSCLC, ClinicalTrials.gov ID NCT04495153
About the Writer
Malavatu Satvika (Linkedin) is a Pharm.D professional and aspiring healthcare medical writer with clinical exposure and research experience. Her interests include medical writing, drug safety, pharmaceutical research, and evidence-based healthcare communication. She has contributed to two research publications in pharmaceutical journals and has gained practical experience in prescription review, patient counselling, medication review, adverse drug reaction monitoring, drug information services, literature review, and clinical documentation through regular hospital training.
She has completed certifications in clinical research, ICH-GCP E6(R3), data management for clinical research, and congenital hypothyroidism. With a strong foundation in pharmacy, clinical practice, and scientific research, she aims to translate complex medical and pharmaceutical information into accurate, clear, and evidence-based healthcare content. She is also preparing to pursue a PhD and further develop her expertise in medical writing and pharmaceutical research.