Intratumoral Gene Mediated Cytotoxic Immunotherapy in Patients With Resectable Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This is a phase I dose escalation study of CAN-2409 plus prodrug in patients with non-small cell lung cancer (NSCLC). The primary clinical objective of the study is to evaluate the safety of CAN-2409 plus prodrug when combined with standard surgery for NSCLC. The primary scientific objective is to determine the immunologic changes induced by CAN-2409 plus prodrug.

Detailed Description
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The purpose of this open-label, dose escalation clinical trial is to investigate the safety of CAN-2409 (aglatimagene besadenovec) plus prodrug prior to surgery in patients with NSCLC. CAN-2409 is a viral immunotherapy approach which utilizes intratumoral administration to selectively induce tumor cell death and elicit both an innate and an adaptive systemic anti-tumor immune response against the injected tumor and uninjected metastases. Local delivery enables these effects while aiming to minimize systemic toxicity. Standard of care surgical resection will be performed about 3 weeks after the CAN-2409 injection. Chemotherapy and/or radiation may begin 6-8 weeks after resection surgery. Choice of chemotherapy depends on the treating oncologist. CAN-2409 (aglatimagene besadenovec) was previously known as AdV-tk, and the combination of CAN-2409 plus prodrug was previously known as GMCI.

Official Title
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Intratumoral Gene Mediated Cytotoxic Immunotherapy (GMCI) For Resectable Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Biological: CAN-2409 + valacyclovir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically documented non-small cell carcinoma (cytology or histology) that is accessible via standard-of-care staging procedures: (1) EBUS or (2) surgical approaches (eg mediastinoscopy, mediastinotomy or VATS). Resectable with negative lymph nodes based on imaging with histologic confirmation at time of the staging procedure prior to AdV-tk injection The tumor must be 4cm or greater in diameter based on imaging ECOG Performance status of 0 or 1. Granulocyte count (ANC) ≥ 1,000/mm3 Peripheral lymphocyte count ≥ 500/mm3 Hemoglobin ≥ 9 g/dl Platelets ≥ 100,000/mm3 Total bilirubin ≤ 1.5 x upper limit of normal SGOT (AST) ≤ 3x upper limit of normal Serum creatinine < 2mg/dl Calculated creatinine clearance > 30ml/min Patients must give study specific informed consent prior to enrollment Exclusion Criteria: Radiotherapy and/or treatment with chemotherapeutic, cytotoxic, or immunologic agents within 4 weeks prior to infusion of the vector. Known immunodeficiency such as HIV infection Active liver disease, including known cirrhosis or active hepatitis Use of systemic corticosteroids (>10 mg prednisone per day or equivalent) or other systemic immunosuppressive drugs Patient is pregnant or breast-feeding. Female patients of childbearing age must have negative serum or urine pregnancy test within 1 week of beginning therapy. Subjects must use acceptable means of birth control until 30 days after the vector injection. Presence of any other life-threatening illness, such as unstable angina, severe oxygen dependence, significant chronic obstructive pulmonary disease (COPD), end-stage liver or renal disease. COPD will be considered significant if disease limits activities of daily living, results in the inability to walk up 1 flight of stair, or requires home oxygen. Presence of known untreated brain metastases. Prior bone marrow transplants (including stem cells) except autologous stem cell transplant without immunosuppression is NOT considered an exclusion. Known sensitivity or allergic reactions to valacyclovir

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Arm<br>CAN-2409 + valacyclovir | Biological: CAN-2409 + valacyclovir<br>* CAN-2409 will be administered intratumorally followed by oral valacyclovir. Valacyclovir will be administered orally at a fixed dose for 14 days after each injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) |  | 5 years | 
| Overall survival (OS) |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aglatimagene besadenovec, CAN-2409, immunotherapy, GMCI, AdV-tk