CAN-2409 Plus Prodrug With Standard of Care Immune Checkpoint Inhibitor for Stage III/IV NSCLC

NCT04495153 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: LuTK02
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 14

Brief Summary

The purpose of this clinical trial is to evaluate the effects of adding CAN-2409 + prodrug for stage III/IV NSCLC patients who are on standard of care first line immune checkpoint inhibitor (ICI) treatment with evidence that the clinical response is inadequate. CAN-2409 is a viral immunotherapy approach that induces tumor-infiltrating T-cells and a consequent PD-L1 up-regulation. A combination of CAN-2409 added to standard of care (SOC) checkpoint inhibitors may lead to improved long-term outcomes for patients with NSCLC who have suboptimal response to ICI therapy.

Conditions

Non Small Cell Lung Cancer

Keywords

Lung cancer; Immunotherapy; GMCI; AdV-tk; aglatimagene besadenovec; CAN-2409

Outcome Measures

Primary Outcomes (2)

• Response rate

  Tumor response as measured by RECIST criteria including overall response rate (ORR) and/or disease control rate (DCR)

  12 months

• Safety graded by CTCAE version 5.0

  Frequency of adverse events

  12 weeks

Secondary Outcomes (5)

• Biomarker Studies

  6 months

• Overall Survival (OS)

  3 years

• Progression Free Survival (PFS)

  3 years

• Changes in patient-reported symptoms using the NSCLC-SAQ

  12 months

• Response rate

  12 months

Study Arms (1)

Cohorts

OTHER

Cohort 1A and 1B - persistent but stable disease at least 18 weeks after starting ICI treatment Cohort 2A and 2B - radiographic progressive disease at least 18 weeks after starting ICI treatment Cohort 3 - refractory disease defined as progressed by imaging at least 9 weeks after starting ICI treatment (CLOSED TO ENROLLMENT)

Biological: Aglatimagene besadenovec

Interventions

Aglatimagene besadenovec BIOLOGICAL

Two courses (Cohort 1A and Cohort 2A) or three courses (Cohort 1B and Cohort 2B) of CAN-2409 injection into an accessible involved tumor site followed by 14 days of prodrug (valacyclovir or acyclovir). For Cohort 1B, the third course is optional. All patients will continue standard of care immune checkpoint inhibitor with or without chemotherapy.

Also known as: CAN-2409, AdV-tk

Cohorts

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with Stage III/IV NSCLC on first line treatment with anti-PD-1/PD-L1 (ICI) +/- chemotherapy for their current stage of disease and fits into one of the following cohorts as determined by investigator, preferably as per RECIST 1.1: Cohort 1) have persistent but stable disease at least 18 weeks after starting ICI treatment, or Cohort 2) have radiographic progressive disease at least 18 weeks after starting ICI treatment
• RECIST evaluable disease including a lesion that is amenable to injection
• Able and willing to undergo a pre-treatment and on-treatment biopsies, if feasible
• ECOG Performance status of 0 or 1
• years of age or older
• Granulocyte count (ANC) ≥ 1,000/mm3
• Hemoglobin ≥ 8 g/dl (patients may be transfused to meet this criterion)
• Platelets ≥ 75,000/mm3
• Total bilirubin ≤ 1.5 x upper limit of normal, except for patients with known Gilbert disease who must have total bilirubin ≤ 3 x upper limit of normal
• SGOT (AST) ≤ 5x upper limit of normal and if elevated, not clinically significant such that ICI can continue
• INR no more than 0.2 above upper limit of normal and aPTT not \>1.2 x upper limit of normal, and value is acceptable for patient to undergo injection procedure. If on anti-coagulation, it must be clinically acceptable to hold anti-coagulation for the injection procedures per investigator discretion
• Serum creatinine \< 2mg/dl and calculated creatinine clearance \> 30ml/min
• Clinically stable and able to continue ICI for at least the 12-week treatment period
• Within 6 months of enrollment, no change of ICI therapy or prior interruptions of more than 4 weeks of current ICI
• Patients should not have received focal therapy (e.g., radiotherapy) at more than three different sites of disease within 12-months prior to enrollment

You may not qualify if:

• Patients with a history of severe immune related adverse events related to ICI
• Patients who require ongoing therapy with disease-modifying antirheumatic drugs (DMARDs), immunomodulators or systemic immunosuppressive drugs including systemic corticosteroids (\>10 mg prednisone per day or equivalent) - premedication for ICI or chemotherapy is allowed
• Patients with a history of active autoimmune disease requiring treatment in the past 2 years
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active hepatitis, or psychiatric illness/social situations that would limit compliance with study requirements
• Women who are pregnant, lactating or intend to become pregnant during the study
• Patients who are known to be HIV positive
• Patients with a history of hypersensitivity or allergic reactions to valacyclovir or acyclovir
• Patients with significant heart disease (New York Heart Association Functional Classification III or IV)
• Patients with continuous oxygen dependence \>2L/min at rest
• Tumor impinging on a neurovascular structure such that inflammation in the site may put patient at risk of compromise as determined by the investigator
• Patients with uncontrolled brain metastases as per investigator
• Patients with liver metastases involving more than half of the liver
• Patients with known EGFR mutation, ALK fusion, or ROS1 fusion positive NSCLC, or that are receiving tyrosine kinase inhibitor (TKI) agents/ALK/ROS1 inhibitors
• Patients with known interstitial lung diseases (ILDs) requiring active therapy (Radiographic fibrosis not requiring therapy is allowed)
• Patients receiving vascular endothelial growth factor (VEGF) inhibitors (including bevacizumab, ramucirumab) within the past 2 months or five half-lives, whichever is longer

Sponsors & Collaborators

• Candel Therapeutics, Inc.: lead
• NYU Langone Health: collaborator

Study Sites (14)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

UConn Health

Farmington, Connecticut, 06030, United States

Location

Yale University, Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Maryland, Baltimore

Baltimore, Maryland, 21201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study is a phase II prospective study to evaluate the safety and potential efficacy of CAN-2409 plus prodrug added to standard of care immune checkpoint inhibitor (ICI) therapy in stage III/IV NSCLC

Study Record Dates

• First Submitted: July 24, 2020
• First Posted: July 31, 2020
• Study Start: October 13, 2020
• Primary Completion: December 31, 2024
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 22, 2025

Record last verified: 2025-08

Locations

US (14)