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

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.

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.

Eligibility Criteria:
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