Phase 3 AURORA Trial Launches to Evaluate Viral Immunotherapy in Advanced NSCLC

Patients with metastatic non–small cell lung cancer (NSCLC) whose disease progresses despite immune checkpoint inhibitor (ICI) therapy continue to face limited treatment options and poor survival outcomes. Candel Therapeutics has now initiated the global pivotal phase 3 AURORA trial (NCT07660094), evaluating the investigational viral immunotherapy aglatimagene besadenovec (CAN-2409) plus valacyclovir (Valtrex; GlaxoSmithKline) in combination with continued pembrolizumab (Keytruda; Merck Sharp & Dohme LLC) compared with standard-of-care docetaxel (Taxotere; sanofi-aventis US LLC) chemotherapy in this difficult-to-treat patient population.^1,2

Global Phase 3 Trial Targets Unmet Need Following ICI Progression

The randomized, open-label AURORA trial will enroll patients with metastatic stage IV nonsquamous NSCLC whose disease has progressed despite prior pembrolizumab-based immunotherapy and platinum-based chemotherapy.² Approximately 150 sites worldwide are expected to participate, with patients randomly assigned 1:1 to receive either intratumoral aglatimagene besadenovec plus oral valacyclovir and continued pembrolizumab or standard-of-care docetaxel chemotherapy.¹

The trial’s primary end point is overall survival, and secondary end points include safety and patient-reported quality-of-life measures using the Non–Small Cell Lung Cancer Symptom Assessment Questionnaire and the EORTC Quality of Life Questionnaire. The FDA has previously granted fast track designation to aglatimagene besadenovec for the treatment of NSCLC.¹

“Patients whose lung cancer progresses despite immune checkpoint inhibitor therapy have limited treatment options, and outcomes with standard chemotherapy remain poor,” Roy S. Herbst, MD, PhD, deputy director and chief of hematology and medical oncology at Yale Cancer Center and co–principal investigator of the study, said in a news release. “The survival results observed with aglatimagene in the phase 2 trial are particularly encouraging and support advancing the program into the pivotal phase 3 AURORA trial.”¹

Encouraging Phase 2 Survival Results Support Pivotal Study

The phase 3 trial builds upon findings from a phase 2 study evaluating aglatimagene besadenovec in patients with advanced NSCLC who experienced inadequate responses to ICIs. Among the 46 patients included in the per-protocol analysis, 50% were alive beyond 24 months despite poor baseline prognostic features.¹

Additionally, among evaluable patients with nonsquamous histology whose disease had progressed despite prior ICI therapy—the intended population for the AURORA study—the median overall survival was 25.4 months.¹ These outcomes compare favorably with historical data demonstrating a median overall survival of 9.8 to 11.8 months for patients receiving docetaxel after progression on first-line immunotherapy.^2-4

“This is a pivotal moment for Candel and, most importantly, for the patients we aim to serve,” Paul Peter Tak, MD, PhD, FMedSci, president and CEO of Candel Therapeutics, said in the release. “Our data suggest that aglatimagene may offer a novel approach by inducing an individualized, systemic antitumor immune response in patients who have very limited therapeutic options.”¹

Novel Viral Immunotherapy Designed to Stimulate Systemic Immune Response

Unlike traditional systemic therapies, aglatimagene besadenovec is an investigational replication-defective adenoviral vector that delivers the HSV-TK gene directly into tumors. Following intratumoral administration, patients receive oral valacyclovir, which is converted into cytotoxic nucleotide analogs within tumor cells expressing HSV-TK, resulting in immunogenic tumor cell death.¹

Beyond direct tumor destruction, the therapy is designed to promote the release of tumor-associated antigens and to trigger local inflammatory signaling via adenoviral proteins. Together, these mechanisms aim to generate a CD8-positive T cell–mediated systemic immune response capable of targeting both injected tumors and distant metastatic lesions.¹

More than 1000 patients have received aglatimagene besadenovec across clinical studies, with a favorable tolerability profile reported to date.¹

Pharmacists May Play a Key Role as Novel Immunotherapies Advance

For oncology pharmacists, investigational multimodal immunotherapies such as aglatimagene besadenovec represent an evolving treatment approach that combines gene-based therapy, antiviral prodrug activation, and immune checkpoint inhibition. If the AURORA trial data demonstrate an overall survival benefit, pharmacists may become increasingly involved in coordinating administration of intratumoral therapy, monitoring toxicities associated with combination immunotherapy, managing oral valacyclovir adherence, and educating patients about these novel treatment strategies.

As ICIs remain foundational therapies for advanced-stage NSCLC, the successful development of treatments that overcome resistance could significantly expand options for patients whose disease progresses after first-line immunotherapy.

REFERENCES

1. Candel Therapeutics announces initiation of global pivotal phase 3 AURORA trial evaluating aglatimagene besadenovec (CAN-2409) in advanced non-small cell lung cancer patients with inadequate response to immune checkpoint inhibitors. News release. Candel Therapeutics. June 30, 2026. Accessed June 30, 2026. https://ir.candeltx.com/news-releases/news-release-details/candel-therapeutics-announces-initiation-global-pivotal-phase-3

2. Aglatimagene besadenovec + prodrug and pembrolizumab vs docetaxel for stage IV non-squamous NSCLC progressing on pembrolizumab (AURORA) (LuTK03). NCT07660094. ClinicalTrials.gov. Updated June 22, 2026. Accessed June 30, 2026. https://clinicaltrials.gov/study/NCT07660094

3. Garon EB, Hellmann MD, Rizvi NA, et al. Five-year overall survival for patients with advanced non‒small-cell lung cancer treated with pembrolizumab: results from the phase I KEYNOTE-001 study. J Clin Oncol. 2019;37(28):2518-2527. doi:10.1200/JCO.19.00934

4. Fossella FV, DeVore R, Kerr RN, et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol. 2000;18(12):2354-2362. doi:10.1200/JCO.2000.18.12.2354