Aglatimagene Besadenovec + Prodrug and Pembrolizumab vs Docetaxel for Stage IV Non-Squamous NSCLC Progressing on Pembrolizumab (AURORA)

Exclusion Criteria31

• 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.
• Has a known history of active autoimmune disease requiring systemic immunosuppressive therapy within the past 2 years is excluded. Note: Participants receiving physiologic corticosteroid replacement (e.g., ≤ 10 mg/day prednisone equivalent) are eligible.
• History of hypersensitivity or allergic reactions to valacyclovir.
• Active, uncontrolled, clinically significant bacterial, fungal, or viral infection, or any ongoing infection requiring systemic therapy.
• Clinically active central nervous system (CNS) metastases or leptomeningeal disease. Evidence of new or progression of CNS confirmed by imaging during the study screening.
• Persistently symptomatic bone metastases.
• Has liver metastases involving more than half of the liver.
• Prior radiotherapy within 2 weeks of the start of the study drug.
• Has a known history of active interstitial lung diseases (ILD) (≥ grade 2) or noninfectious pneumonitis requiring active therapy, or for whom suspected ILD/pneumonitis cannot be ruled out by imaging at screening, or clinically severe pulmonary compromise due to intercurrent pulmonary illness and/or pulmonary disorder (e.g., severe chronic obstructive pulmonary disease, restrictive lung disease, etc.) requiring supplemental oxygen (>2L/min at rest) or any autoimmune, connective tissue or inflammatory disorders with active pulmonary involvement (i.e., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or any prior pneumonectomy.
• Receiving or anticipated to receive investigational agents or has used an investigational device within 4 weeks prior to the first dose of study drug.
• Ongoing clinically significant toxicity (> Grade 2 except alopecia), associated with prior treatment including systemic therapy, radiotherapy, or surgery.
• Has a known history of Human Immunodeficiency Virus (HIV) infection and/or acquired immunodeficiency syndrome (AIDS)-related illness.
• Has a known active or known prior history of Hepatitis B (HBV) infection (e.g., hepatitis B virus surface antigen \[HBsAg\] reactive or detectable quantitative levels of HBV DNA) or known active Hepatitis C (HCV) (e.g., hepatitis C virus RNA \[quantitative\] is detected).
• Has an uncontrolled or significant heart disease, defined as:
• Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) prolongation > 470 msec (based on the average of Screening triplicate 12-lead electrocardiogram \[ECG\] determinations).
• Myocardial infarction or uncontrolled/unstable angina within 6 months before randomization.
• Congestive heart failure (CHF) (New York Heart Association \[NYHA\] Class II to IV) at Screening (see Appendix 12.3).
• Uncontrolled or significant cardiac arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication).
• NYHA Class III or IV Functional Classification.
• LVEF < 40% by ECHO or MUGA scan within 28 days before randomization.
• Uncontrolled hypertension (resting systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg) within 28 days before randomization.
• Has a concurrent malignancy requiring active systemic or local anti-cancer treatment except for the following:
• Adequately treated non-melanoma skin cancer (squamous or basal cell cancers).
• In situ cervical cancer that has been adequately treated.
• Early-stage malignancies under active surveillance or observation only, including but not limited to:
• Low-risk prostate cancer managed with active surveillance- Ductal carcinoma in situ of the breast managed with observation
• Participants of childbearing potential, who are pregnant, lactating, or intend to become pregnant or father children during the study.
• Any other significant physical and medical co-morbid conditions, including psychiatric conditions that, in the opinion of the Investigator, would impair study participation or cooperation.