A Phase 3, Multicenter, Randomized, Controlled, Open-Label Clinical Trial of Aglatimagene Besadenovec (CAN-2409) Plus Prodrug and Pembrolizumab Versus Docetaxel for Stage IV Non-Squamous Non-Small Cell Lung Cancer Progressing on Pembrolizumab-based Treatment
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).
• Note: Able to be reached by bronchoscopy (including robotic bronchoscopy or flexible bronchoscopy with or without endobronchial ultrasound), or by percutaneous injection.
• 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.
• Note: Participants on a pembrolizumab-based regimen should have achieved a best overall response (BOR) of at least SD (e.g., participants with a BOR of PD while on pembrolizumab are not eligible).
• Prior treatment requirements:
∙ Must have received platinum-based chemotherapy in any line of therapy.
‣ May have received pembrolizumab therapy in combination with chemotherapy or sequentially. Note: The participant must be currently progressing on pembrolizumab or a pembrolizumab-based regimen.
• ECOG performance status of 0 or 1 at screening.
• Has adequate bone marrow function, defined as:
∙ Platelet count ≥ 75,000/mm3.
‣ Hemoglobin ≥ 9.0 g/dL (
‣ Absolute neutrophil count (ANC) ≥ 1500/mm3
• Has adequate organ function, defined as: a) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ×upper limit of normal (ULN); (≤ 5.0 × ULN if transferase elevation is due to liver metastases) AND b) Total bilirubin ≤ 1.5 × ULN (\< 3.0 × ULN in the presence of documented Gilbert's syndrome \[unconjugated hyperbilirubinemia\] or liver metastases at baseline). c) Creatinine clearance ≥ 30 mL/min as calculated using the Cockcroft-Gault equation). d) International normalized ratio (INR) \< 1.5 without anticoagulants, INR \< 3 if on prophylactic anticoagulation therapy.
• e) Prothrombin time (PT) and either partial thromboplastin (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
• Completion of prior therapy with required washout and recovery:
‣ Cytotoxic chemotherapy: \> 14 days from the last dose.
⁃ Monoclonal antibodies (e.g., bevacizumab, ramucirumab): ≥ 5 half-lives or ≥ 42 days, whichever is longer.
⁃ Recovered to ≤ Grade 1 from prior therapy-related clinical toxicities (except alopecia and stable endocrine replacement).
⁃ Projected life expectancy ≥ 12 weeks (or 3 months) in the opinion of the Investigator.
⁃ Pregnancy test (for females of childbearing potential) negative at screening.
⁃ Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.