Phase 3 CAN-2409 HSV-tk adenoviral gene therapy + prodrug with PD-1 blockade in NSCLC

Candel Therapeutics’ Phase 3 AURORA trial randomizes patients 1:1 to either intratumoral aglatimagene besadenovec (CAN-2409)—a replication-deficient adenoviral vector delivering the HSV-tk “suicide gene”—plus oral valacyclovir (an antiviral DNA polymerase inhibitor used here as the HSV-tk–activated prodrug partner) with continued pembrolizumab (Merck/MSD; PD-1 monoclonal antibody), versus standard docetaxel chemotherapy (a microtubule/tubulin inhibitor). The purpose is to test whether adding local gene-mediated tumor killing plus immune priming can restore or deepen checkpoint benefit after progression on prior pembrolizumab-based platinum chemoimmunotherapy in metastatic (stage IV), non-squamous NSCLC. It is open-label and controlled, with overall survival as a key outcome. The scientific/commercial angle is a registrational attempt to “rescue” post–PD-1 progression using an intratumoral gene therapy platform rather than another systemic checkpoint combo. Today’s care after progression on first-line pembrolizumab + platinum is typically single-agent chemo such as docetaxel (often with ramucirumab in some practices) or other later-line systemic options, with limited durability.