Candel Therapeutics publishes Phase 2a NSCLC data showing 24.5-month mOS

Candel Therapeutics has published final Phase 2a data for its lead immunotherapy candidate aglatimagene besadenovec in advanced non-small cell lung cancer, reporting a median overall survival of 24.5 months in patients whose disease had failed to respond adequately to immune checkpoint inhibitors. The results appear in the Journal for ImmunoTherapy of Cancer and represent the first peer-reviewed publication of the full dataset from trial NCT04495153.

The figure compares favourably with the current standard of care in this setting. Published trials of docetaxel chemotherapy in ICI-refractory NSCLC report median overall survival of 9.8 to 11.8 months, meaning the evaluable population in the aglatimagene study achieved roughly double that duration. Among the 41 patients with confirmed progressive disease at baseline despite prior ICI therapy, median overall survival reached 21.5 months, and 37% remained alive beyond 24 months at the time of data cutoff.

Mechanism and subgroup findings

Aglatimagene is an off-the-shelf, replication-defective adenovirus that delivers the herpes simplex virus thymidine kinase gene directly into tumour tissue. On administration of the prodrug valacyclovir, the enzyme triggers immunogenic cell death and releases tumour neoantigens, while the adenoviral capsid proteins stimulate a broader pro-inflammatory cascade. The net effect, the company says, is an in-situ vaccine that primes CD8+ T cells against both the injected lesion and distant metastases.

That systemic effect was visible in the data. Among the 35 evaluable patients with more than one measurable lesion, 69% showed reduction of uninjected tumours, an abscopal response rate the investigators describe as notable. Biomarker work confirmed elevated granzyme B and granzyme H levels, expanded peripheral CD8+ effector T cells, and increased cytotoxic infiltration of tumour tissue, with the strongest signals following the second aglatimagene injection.

Non-squamous histology emerged as the clearest predictor of benefit. In the 33-patient non-squamous subgroup with progressive disease on ICI, median overall survival climbed to 25.4 months. Among patients surviving beyond 24 or 30 months, the non-squamous proportion was striking: 14 of 15 and 9 of 9, respectively. The company's pivotal Phase 3 AURORA trial is consequently restricted to metastatic non-squamous NSCLC, comparing aglatimagene plus valacyclovir combined with continued pembrolizumab against docetaxel across approximately 150 sites worldwide.

Competitive context and regulatory path

The ICI-refractory NSCLC space has attracted growing attention as a post-checkpoint treatment gap that conventional chemotherapy addresses poorly. Several viral and cell-based immunotherapy approaches are in development for this population, including tumour-infiltrating lymphocyte therapies and other oncolytic platforms, though none has yet secured regulatory approval specifically in this line. Aglatimagene holds FDA Fast Track Designation in NSCLC, which provides for more frequent agency interactions and rolling review eligibility, but confers no guarantee of approval.

Charu Aggarwal, Leslye Heisler Professor of Medicine at the University of Pennsylvania's Perelman School of Medicine and the trial's lead investigator, said: "The magnitude of benefit observed, particularly in patients with non-squamous disease, is striking, and represents an important potential advance for this patient population."

The safety profile reported across 46 evaluable patients was broadly manageable. The most frequent adverse events were grade 1 and 2 flu-like symptoms including fatigue, nausea and pyrexia. Grade 3 treatment-related adverse events occurred in 13.7% of patients, and no dose-limiting toxicities were identified during extended follow-up. Candel notes that more than 1,000 patients have now received aglatimagene across its clinical programme, building a tolerability database relevant to the AURORA readout. Enrolment timelines and an expected data readout window for the Phase 3 study were not disclosed in the release.