Intratumoral Gene Mediated Cytotoxic Immunotherapy in Patients With Resectable Non-Small Cell Lung Cancer
Study Details
Study Description
Brief Summary
This is a phase I study of Gene Mediated Cytotoxic Immunotherapy (GMCI) in patients with non-small cell lung cancer (NSCLC). The primary clinical end-point of the study is to evaluate the safety of GMCI when combined with standard surgery for NSCLC. The primary scientific objective is to determine the immunologic changes induced by GMCI.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
The purpose of this open-label, dose escalation clinical trial is to investigate the safety of GMCI prior to surgery in patients with NSCLC. GMCI involves the use of aglatimagene besadenovec (AdV-tk) injected into the tumor followed by oral valacyclovir prodrug to kill tumor cells and stimulate a cancer vaccine effect. Killing tumor cells in an immune stimulatory environment induces the body's immune system to detect and destroy cancer cells. GMCI has been well tolerated in previous trials in multiple tumor types with clinical, pathologic and immune responses.
AdV-tk will be injected intratumorally on day 0 during a standard of care staging procedure. The prodrug, valacyclovir, will be administered orally at a fixed dose for 14 days following the AdV-tk injection. Then standard of care surgical resection will be performed about 3 weeks after the AdV-tk injection. Chemotherapy and/or radiation may begin 6-8 weeks after resection surgery. Choice of chemotherapy depends on the treating oncologist.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Study Arm AdV-tk (aglatimagene besadenovec) + valacyclovir |
Biological: AdV-tk (aglatimagene besadenovec) + valacyclovir
AdV-tk will be administered intratumorally followed by oral valacyclovir. Valacyclovir will be administered orally at a fixed dose for 14 days after each AdV-tk administration.
|
Outcome Measures
Primary Outcome Measures
- Safety [6 weeks]
Safety based on standard laboratory and clinical adverse event monitoring.
Secondary Outcome Measures
- Immunologic changes [12 months]
The effect of GMCI on the histology and immune profile of the resected tumor. Systemic and intratumoral cytokine responses will also be assessed.
- Progression free survival (PFS) [5 years]
The PFS curves will be estimated using the Kaplan-Meier method.
- Overall survival (OS) [5 years]
The OS curves will be estimated using the Kaplan-Meier method.
Eligibility Criteria
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).
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Resectable with negative lymph nodes based on imaging with histologic confirmation at time of the staging procedure prior to AdV-tk injection
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The tumor must be 4cm or greater in diameter based on imaging
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ECOG Performance status of 0 or 1.
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Granulocyte count (ANC) ≥ 1,000/mm3
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Peripheral lymphocyte count ≥ 500/mm3
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Hemoglobin ≥ 9 g/dl
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Platelets ≥ 100,000/mm3
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Total bilirubin ≤ 1.5 x upper limit of normal
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SGOT (AST) ≤ 3x upper limit of normal
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Serum creatinine < 2mg/dl
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Calculated creatinine clearance > 30ml/min
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Patients must give study specific informed consent prior to enrollment
Exclusion Criteria:
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Radiotherapy and/or treatment with chemotherapeutic, cytotoxic, or immunologic agents within 4 weeks prior to infusion of the vector.
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Known immunodeficiency such as HIV infection
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Active liver disease, including known cirrhosis or active hepatitis
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Use of systemic corticosteroids (>10 mg prednisone per day or equivalent) or other systemic immunosuppressive drugs
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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.
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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.
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Presence of known untreated brain metastases.
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Prior bone marrow transplants (including stem cells) except autologous stem cell transplant without immunosuppression is NOT considered an exclusion.
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Known sensitivity or allergic reactions to valacyclovir
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
Sponsors and Collaborators
- Candel Therapeutics, Inc.
- University of Pennsylvania
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- LuTK01