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.
Parallel
Aglatimagene Besadenovec
Biological/Vaccinevia intratumoral injections into lung or lymph nodes at two timepoints
Valacyclovir
DrugOral, for14 days following each aglatimagene besadenovec injection
Pembrolizumab
Biological/Vaccineevery 3 weeks (Q3W) or every 6 weeks (Q6W)
Docetaxel
Drugevery 21 days with standard premedication
Overall Survival
To evaluate whether treatment with aglatimagene besadenovec (CAN-2409) plus valacyclovir and continued pembrolizumab improves overall survival (OS) compared to standard of care (SoC) docetaxel chemotherapy, in participants with Stage IV non-squamous non-small cell lung cancer (NSCLC) whose disease has progressed following prior pembrolizumab-based platinum chemoimmunotherapy
Time to meaningful deterioration based on the Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) Total Score
Defined as the time from randomization until a definitive clinically meaningful worsening in symptoms or in NSCLC-SAQ total score. The lowest score possible is 0, and the highest score possible is 20. Higher score indicates more severe symptoms.
Change from baseline of Total Score of NSCLC-SAQ at Week 12
NSCLC-SAQ Total Score after Week 12 compared to baseline. The lowest score possible is 0, and the highest score possible is 20. Higher score indicates more severe symptoms.
Change from baseline of Global Health Status/QoL Score of EORTC-QLQ-30 at Week 12
EORTC-QLQ-30 Global Health Status/QoL Score after Week 12 compared to baseline. The lowest score possible is 0, and the highest score possible is 100. Higher score indicates less severe symptoms.
Frequency of Treatment Emergent Adverse Events (TEAEs) graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
Treatment Emergent Adverse Events (TEAEs) graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
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