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

Overview

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.

Full Title of Study: “Intratumoral Gene Mediated Cytotoxic Immunotherapy (GMCI) For Resectable Non-Small Cell Lung Cancer”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 1, 2021

Detailed Description

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.

Interventions

  • Biological: CAN-2409 + valacyclovir
    • 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.

Arms, Groups and Cohorts

  • Experimental: Study Arm
    • CAN-2409 + valacyclovir

Clinical Trial Outcome Measures

Primary Measures

  • Incidence of treatment emergent adverse events
    • Time Frame: 6 weeks

Secondary Measures

  • Progression free survival (PFS)
    • Time Frame: 5 years
  • Overall survival (OS)
    • Time Frame: 5 years

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Candel Therapeutics, Inc.
  • Collaborator
    • University of Pennsylvania
  • Provider of Information About this Clinical Study
    • Sponsor

Citations Reporting on Results

Predina JD, Haas AR, Martinez M, O'Brien S, Moon EK, Woodruff P, Stadanlick J, Corbett C, Frenzel-Sulyok L, Bryski MG, Eruslanov E, Deshpande C, Langer C, Aguilar LK, Guzik BW, Manzanera AG, Aguilar-Cordova E, Singhal S, Albelda SM. Neoadjuvant Gene-Mediated Cytotoxic Immunotherapy for Non-Small-Cell Lung Cancer: Safety and Immunologic Activity. Mol Ther. 2021 Feb 3;29(2):658-670. doi: 10.1016/j.ymthe.2020.11.001. Epub 2020 Nov 5.

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