Candel Therapeutics opens Phase 3 AURORA trial for CAN-2409 in NSCLC
Candel Therapeutics has initiated the global pivotal Phase 3 AURORA trial (NCT07660094), enrolling patients with metastatic non-squamous non-small cell lung cancer whose disease has progressed despite pembrolizumab and platinum-based chemotherapy. The Needham, Massachusetts-based company said the first site is now open, with enrolment expected to span approximately 150 sites worldwide.
The trial randomises patients 1:1 to receive either aglatimagene besadenovec (CAN-2409) plus valacyclovir alongside continued pembrolizumab, or standard-of-care docetaxel chemotherapy. The primary endpoint is overall survival, with secondary endpoints covering safety and patient-reported quality of life using the NSCLC-SAQ and EORTC QLQ-30 instruments. Candel has engaged Parexel International as its clinical research organisation to manage global site operations.
Trial rationale and Phase 2 data
The AURORA programme builds on a completed Phase 2 study in which 50% of 46 per-protocol patients survived beyond 24 months after failing immune checkpoint inhibitor therapy, a population carrying multiple adverse prognostic factors. In the non-squamous subgroup with progressive disease at baseline, the reported median overall survival was 25.4 months. That compares favourably with the 9.8 to 11.8 months median overall survival typically delivered by docetaxel in this setting, according to published data cited by the company.
Aglatimagene is an off-the-shelf, replication-defective adenovirus engineered to deliver the herpes simplex virus thymidine kinase gene intratumorally. The mechanism relies on HSV-tk converting the prodrug valacyclovir into nucleotide analogues that drive immunogenic cell death, while the adenoviral capsid simultaneously promotes pro-inflammatory signalling. The resulting CD8+ T cell response is intended to act both at the injected lesion and at distant metastases through what Candel describes as in situ immunisation. More than 1,000 patients have received aglatimagene across clinical programmes to date. The FDA previously granted Fast Track Designation for the NSCLC indication.
Roy Herbst, Deputy Director and Chief of Medical Oncology and Hematology at Yale Cancer Center and co-Principal Investigator, said: "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."
Market context and competitive landscape
The unmet need in ICI-refractory NSCLC is significant. Roughly 60% of NSCLC patients without actionable mutations experience disease progression within one year of first-line checkpoint inhibitor therapy, leaving docetaxel as the dominant second-line option despite its modest survival benefit. That gap has attracted considerable industry interest, with antibody-drug conjugates, bispecific antibodies and other immune-priming strategies in various stages of development across a number of academic spinouts and established oncology companies.
Viral immunotherapy as a modality remains less crowded. Candel's adenovirus-based platform is positioned by the company as potentially first-in-class in this indication, though clinical validation at the Phase 3 level will be the definitive test. The AURORA design, with overall survival as the primary endpoint and a docetaxel comparator arm, is consistent with what regulators typically require for a label in this setting, which should reduce the risk of an approvability dispute if the survival data are positive.
Candel also carries an ongoing Phase 1b programme in recurrent high-grade glioma using its separate HSV-based candidate, linoserpaturev, and has previously completed a Phase 3 trial of aglatimagene in localised prostate cancer. Investors will be focused on AURORA enrolment pace and interim safety data as the programme scales across its global site network.