This phase III trial compares the effect of the combination of aglatimagene besadenovec and pembrolizumab versus standard of care docetaxel chemotherapy for the treatment of stage IV non-squamous, non-small cell lung cancer. Aglatimagene besadenovec is a replication-deficient adenoviral vector encoding the herpes simplex virus thymidine kinase (HSV-tk) gene. When combined with an oral prodrug (valacyclovir), injection of aglatimagene induces targeted tumor cell death and stimulates a systemic immune response. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial may help doctors find out if giving aglatimagene with pembrolizumab is more effective at treating patients with stage IV non-squamous, non-small cell lung cancer than standard chemotherapy.
Age ≥ 18 years, at the time of signing the informed consent.
Histologically confirmed metastatic Stage IV non-squamous NSCLC.
Measurable disease per RECIST v1.1 with at least 1 thoracic lesion amenable to intratumoral injection (e.g., pathological lymph node or lung lesion).
Documented radiographic progression observed in at least 3 consecutive scans or according to RECIST v1.1 criteria after a minimum of 12 weeks on continued pembrolizumab, determined by central review.
Has a known actionable genomic alteration, including EGFR, ALK, or ROS1 rearrangements, for which approved targeted therapy exists. Participants who are receiving or have previously received tyrosine kinase inhibitor (TKI) therapy targeting EGFR, ALK, or ROS1 are excluded.
Prior therapy with docetaxel either as monotherapy or in combination with other agents.
Prior treatment with CTLA-4 inhibitor (e.g., ipilimumab).
History of severe irAEs related to ICI.