On October 1, 2026 Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical-stage biopharmaceutical company focused on developing multimodal immunotherapies to improve disease outcomes for patients with cancer, reported the publication of final phase 2a clinical trial results (NCT04495153) of aglatimagene besadenovec (aglatimagene) plus valacyclovir in patients with stage III/IV NSCLC who had shown inadequate response to ICI. The trial demonstrated a median overall survival (mOS) of 24.5 months in the evaluable population, substantially exceeding historical benchmarks for standard-of-care docetaxel chemotherapy in this patient population.

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The data is published in the Journal for ImmunoTherapy of Cancer, a leading peer-reviewed oncology journal, providing independent validation of the clinical significance of aglatimagene in patients with advanced NSCLC with an inadequate response to ICI.

Patients with unresectable stage III/IV NSCLC who progress on ICI face limited treatment options and poor survival outcomes. Current standard of care with docetaxel chemotherapy yields a median overall survival of only 9.8 to 11.8 months in this population.1,2 The phase 2a trial enrolled 46 evaluable patients receiving two courses of aglatimagene plus valacyclovir in combination with continued ICI therapy (per protocol population). Among patients with progressive disease at baseline despite ICI treatment (cohort 2, n=41), mOS was 21.5 months. Notably, 37% of patients with progressive disease on ICI remained alive beyond 24 months at the time of data cutoff, demonstrating a prolonged survival tail not typically observed in this setting.

Non-squamous NSCLC has also emerged as a key predictor of enhanced clinical benefit. In the evaluable population of patients with non-squamous histology and progressive disease on ICI (n=33), mOS reached 25.4 months, with 14 of 15 patients surviving beyond 24 months and 9 of 9 patients surviving beyond 30 months having non-squamous disease. Exploratory analysis in the intention-to-treat cohort of non-squamous patients showed mOS of 16.7 months, still longer than the 12.3-month benchmark reported with docetaxel in this setting in published trials.

Mechanistic studies revealed systemic immune activation following treatment. Among evaluable patients with >1 lesion (n=35), 69% exhibited systemic clinical response with reduction of uninjected lesions, indicating an abscopal response. Biomarker analysis demonstrated increased cytotoxic T cell infiltration in tumor tissue, expansion of activated CD8+ effector and central memory T cells in peripheral blood, and elevated serum levels of granzymes after the second aglatimagene injection, with changes most pronounced following the second administration. Multi-omics factor analysis identified coordinated immune activation patterns associated with improved survival. Patients who survived beyond 24 months exhibited significantly higher levels of key immune markers, including granzyme B and granzyme H, compared to those who died earlier.

Treatment with aglatimagene plus valacyclovir was generally well tolerated, with the most common adverse events being mild flu-like symptoms (fatigue, nausea, pyrexia) that were predominantly grade 1 and 2. Grade 3 treatment-related adverse events were reported in 13.7% of patients. No dose-limiting toxicities or unexpected safety signals were identified during extended follow-up.

"These peer-reviewed results confirm that aglatimagene has the potential to extend survival for patients with advanced non-small cell lung cancer who have limited options after immune checkpoint inhibitors fail to control their cancer," said Charu Aggarwal, MD, MPH, Leslye Heisler Professor of Medicine at the University of Pennsylvania’s Perelman School of Medicine and lead investigator of the trial. "The magnitude of benefit observed, particularly in patients with non-squamous disease, is striking, and represents an important potential advance for this patient population."

Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel commented, "Aglatimagene’s ability to reinvigorate anti-tumor immunity in checkpoint-refractory patients through a systemic immune response, combined with its favorable safety profile, positions this approach as a potentially transformative option for patients with limited therapeutic alternatives. These results support the advancement of our pivotal phase 3 AURORA trial, which is enrolling patients globally."

The global phase 3 AURORA trial is enrolling patients across approximately 150 sites worldwide. The trial is evaluating aglatimagene plus valacyclovir in combination with continued pembrolizumab versus standard-of-care docetaxel in patients with metastatic stage IV non-squamous NSCLC who have experienced disease progression despite prior pembrolizumab and platinum-based chemotherapy.

About aglatimagene besadenovec

Aglatimagene, Candel’s most advanced multimodal biological immunotherapy candidate, is an investigational, off-the-shelf, replication-defective adenovirus designed to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene to a patient’s tumor. After intratumoral administration, HSV-tk enzyme activity results in conversion of prodrug (valacyclovir) into deoxyribonucleic acid (DNA)-incorporating nucleotide analogs, leading to immunogenic cell death in cells exhibiting DNA damage and proliferating cells, with subsequent release of a variety of tumor (neo)antigens in the tumor microenvironment. At the same time, the adenoviral serotype 5 capsid proteins promote inflammation through the induction of expression of pro-inflammatory cytokines, chemokines, and adhesion molecules. Together, this regimen is designed to induce an individualized and specific CD8+ T cell-mediated response against the injected tumor and uninjected distant metastases for broad anti-tumor activity, based on in situ immunization against a variety of tumor antigens. Aglatimagene has the potential to treat a broad range of solid tumors. Encouraging monotherapy activity as well as combination activity with standard of care radiotherapy, surgery, chemotherapy, and immune checkpoint inhibitors have previously been shown in several nonclinical and clinical settings. More than 1,000 patients have been dosed with aglatimagene in clinical trials with a favorable tolerability profile to date, supporting the potential for use with standard of care, when indicated. Aglatimagene is currently not approved by the U.S. Food and Drug Administration (FDA) or any other regulatory authority for any use.

(Press release, Candel Therapeutics, OCT 1, 2026, View Source [SID1234671221])