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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04495153
Recruitment Status : Recruiting
First Posted : July 31, 2020
Last Update Posted : May 10, 2023
NYU Langone Health
Information provided by (Responsible Party):
Candel Therapeutics, Inc.

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.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Biological: Aglatimagene besadenovec Phase 2

Detailed Description:

This clinical trial evaluates the addition of CAN-2409 plus prodrug for stage III/IV NSCLC patients who are on standard of care first line ICI (anti-PD-1/PD-L1) but with evidence of suboptimal response (either disease progression or stable disease at time of study enrollment). CAN-2409 plus prodrug has been shown to increase the response rate to ICI in animal studies. Safety and tolerability of CAN-2409 plus prodrug has been demonstrated in clinical trials in over 950 patients with cancer, including cancers of the lung, pancreas, prostate, and brain. Initial proof of mechanism has been shown in non-small lung cancer, prostate cancer, high-grade glioma, and pancreatic cancer. The eligibility criterion in the current clinical trial is based on time on ICI and response status with cohorts as follows:

Cohort 1A and 1B: patients with stable disease radiographically at least 18 weeks after starting ICI treatment and who are clinically stable

Cohort 2A and 2B: patients with evidence of radiographic progression at least 18 weeks after starting ICI treatment but who are clinically stable.

Cohort 3, which is now closed for enrollment, was for patients who had evidence of radiographic progression at least 9 weeks after starting ICI but who were clinically stable.

The specific ICI treatment regimen is not specified to allow for different standard of care options with or without chemotherapy; for example, pembrolizumab alone, pembrolizumab plus chemotherapy, or atezolizumab/chemotherapy. In addition, it allows stage III patients after chemoradiation who may be on durvalumab as their standard of care. For example, a stage III patient may be eligible for cohort 2 if they have radiographic progression but are clinically stable 18 weeks after starting durvalumab.

The release of Version 05 of the protocol increased enrollment numbers into Cohorts 1 and 2 (from target n=32 evaluable to n=40 evaluable), while closing Cohort 3. In Amendment 6, cohort 1B and 2B were initiated to evaluate a 3-dose regimen of CAN-2409 + prodrug. Adjustments to the sample size extended the anticipated primary completion date for this trial.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 86 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: 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
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: CAN-2409 Plus Prodrug With Standard of Care Immune Checkpoint Inhibitor for Stage III/IV NSCLC Patients
Actual Study Start Date : October 13, 2020
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2026

Resource links provided by the National Library of Medicine

Arm Intervention/treatment

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
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.
Other Names:
  • CAN-2409
  • AdV-tk

Primary Outcome Measures :
  1. Response rate [ Time Frame: 12 months ]
    Tumor response as measured by RECIST criteria including overall response rate (ORR) and/or disease control rate (DCR)

  2. Safety graded by CTCAE version 5.0 [ Time Frame: 12 weeks ]
    Frequency of adverse events

Secondary Outcome Measures :
  1. Biomarker Studies [ Time Frame: 6 months ]
    Blood and tumor will be evaluated for changes in immune response before and after CAN-2409 + prodrug

  2. Overall Survival (OS) [ Time Frame: 3 years ]
    Defined as time from date of first dose of CAN-2409 to death by any cause (OS-1). An additional OS will be defined as time from ICI treatment initiation to death due to any cause (OS-2).

  3. Progression Free Survival (PFS) [ Time Frame: 3 years ]
    Defined as time from date of first dose of CAN-2409 to post-treatment progression or death by any cause (PFS-1). An additional PFS estimate will be calculated from ICI treatment initiation (PFS-2).

  4. Changes in patient-reported symptoms using the NSCLC-SAQ [ Time Frame: 12 months ]
    Non-small Cell Lung Cancer Symptoms Assessment Questionnaire (NSCLC-SAQ) score after compared to before treatment. The lowest score possible is 0, and the highest score possible is 20. Higher score indicates more severe symptoms.

  5. Response rate [ Time Frame: 12 months ]
    Tumor Response as measured by iRECIST criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. 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
  2. RECIST evaluable disease including a lesion that is amenable to injection
  3. Able and willing to undergo a pre-treatment and on-treatment biopsies, if feasible
  4. ECOG Performance status of 0 or 1
  5. 18 years of age or older
  6. Granulocyte count (ANC) ≥ 1,000/mm3
  7. Hemoglobin ≥ 8 g/dl (patients may be transfused to meet this criterion)
  8. Platelets ≥ 75,000/mm3
  9. 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
  10. SGOT (AST) ≤ 5x upper limit of normal and if elevated, not clinically significant such that ICI can continue
  11. 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
  12. Serum creatinine < 2mg/dl and calculated creatinine clearance > 30ml/min
  13. Clinically stable and able to continue ICI for at least the 12-week treatment period
  14. Within 6 months of enrollment, no change of ICI therapy or prior interruptions of more than 4 weeks of current ICI
  15. Patients should not have received focal therapy (e.g., radiotherapy) at more than three different sites of disease within 12-months prior to enrollment
  16. Patients must give study specific informed consent prior to enrollment and any study specific procedures

Exclusion Criteria:

  1. Patients with a history of severe immune related adverse events related to ICI
  2. 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
  3. Patients with a history of active autoimmune disease requiring treatment in the past 2 years
  4. 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
  5. Women who are pregnant, lactating or intend to become pregnant during the study
  6. Patients who are known to be HIV positive
  7. Patients with a history of hypersensitivity or allergic reactions to valacyclovir or acyclovir
  8. Patients with significant heart disease (New York Heart Association Functional Classification III or IV)
  9. Patients with continuous oxygen dependence >2L/min at rest
  10. Tumor impinging on a neurovascular structure such that inflammation in the site may put patient at risk of compromise as determined by the investigator
  11. Patients with uncontrolled brain metastases as per investigator
  12. Patients with liver metastases involving more than half of the liver
  13. Patients with known EGFR mutation, ALK fusion, or ROS1 fusion positive NSCLC, or that are receiving tyrosine kinase inhibitor (TKI) agents/ALK/ROS1 inhibitors
  14. Patients with known interstitial lung diseases (ILDs) requiring active therapy (Radiographic fibrosis not requiring therapy is allowed)
  15. Patients receiving vascular endothelial growth factor (VEGF) inhibitors (including bevacizumab, ramucirumab) within the past 2 months or five half-lives, whichever is longer
  16. Patients must have no concurrent malignancy requiring treatment (except squamous or basal cell skin cancers)
  17. Patients without contrast enhanced imaging at baseline or those with contraindication to the use of contrast.
  18. Patients who are pregnant, breastfeeding, or plan to become pregnant.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04495153

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United States, Arizona
Mayo Clinic Hospital Recruiting
Phoenix, Arizona, United States, 85054
Contact: Panayiotis Savvides, MD, PhD    480-933-6836    Savvides.Panayiotis@mayo.edu   
Principal Investigator: Kenneth Sakata, MD         
United States, Connecticut
UConn Health Recruiting
Farmington, Connecticut, United States, 06030
Contact: Quratulain (Annie) Ali    860-679-7648    qali@uchc.edu   
Principal Investigator: Omar Ibrahim, MD         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Paige Pribble    773-702-4983    Ppribble@bsd.uchicago.edu   
Principal Investigator: Christine Bestvina, MD         
United States, Maryland
University of Maryland, Baltimore Recruiting
Baltimore, Maryland, United States, 21201
Contact: Maha Khalil    410-328-5009    mkhalil@umm.edu   
Principal Investigator: Ranee Mehra, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Travis Fisher    507-538-1960    fisher.travis1@mayo.edu   
Contact: Karlyn Pierson       Pierson.Karlyn@mayo.edu   
Principal Investigator: Janani Reisenauer, MD         
United States, New York
NYU Langone Health Recruiting
New York, New York, United States, 10016
Contact: NYU Clinicaltrials.gov Group    929-455-2453    CT.gov@nyulangone.org   
Principal Investigator: Daniel H. Sterman, MD FCCP, ATSF         
United States, Ohio
Cleveland Clinic Withdrawn
Cleveland, Ohio, United States, 44106
The Ohio State University Wexner Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Carly Pilcher    614-685-5414    Carly.Pilcher@osumc.edu   
Principal Investigator: Jasleen Pannu, MBBS         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Melissa Volpe    215-220-9703    Melissa.Volpe@pennmedicine.upenn.edu   
Principal Investigator: Charu Aggarwal, MD, MPH         
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Clinical Trials Information Program    800-811-8480    CIP@vumc.org   
Principal Investigator: Fabien Maldonado, MD         
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Jhankruti Zaveri    713-745-2645    jzaveri@mdanderson.org   
Principal Investigator: George Eapen, MD         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Kaitlin Stephens    801-213-8494    kaitlin.stephens@hci.utah.edu   
Principal Investigator: Sonam Puri, MD         
United States, Virginia
Hunter Holmes McGuire VA Medical Center Recruiting
Richmond, Virginia, United States, 23249
Contact: Krista Chafin    804-675-5625    krista.chafin@va.gov   
Principal Investigator: Leigh Swartz, MD         
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: Melissa Schaefer    804-827-1025    masseylung@vcu.edu   
Principal Investigator: Erin Alesi, MD         
Sponsors and Collaborators
Candel Therapeutics, Inc.
NYU Langone Health
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Responsible Party: Candel Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04495153    
Other Study ID Numbers: LuTK02
First Posted: July 31, 2020    Key Record Dates
Last Update Posted: May 10, 2023
Last Verified: May 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Candel Therapeutics, Inc.:
Lung cancer
aglatimagene besadenovec
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms