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

Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03131037
• Other study ID #: LuTK01
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 4, 2017
• Est. completion date: December 2024

Study information

• Verified date: August 2023
• Source: Candel Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 12
• Est. completion date: December 2024
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Candel Therapeutics, Inc.	University of Pennsylvania

Country where clinical trial is conducted

United States, 

References & Publications (1)

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-Media — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment emergent adverse events		6 weeks
Secondary	Progression free survival (PFS)		5 years
Secondary	Overall survival (OS)		5 years

External Links

•   Neoadjuvant Gene-Mediated Cytotoxic Immunotherapy for Non-Small-Cell Lung Cancer: Safety and Immunologic Activity