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GMCI Plus 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. Identifier: NCT04495153
Recruitment Status : Recruiting
First Posted : July 31, 2020
Last Update Posted : March 29, 2022
NYU Langone Health
Information provided by (Responsible Party):
Candel Therapeutics, Inc.

Brief Summary:
The purpose of this phase 2 multi-site trial is to evaluate the safety and efficacy of adding Gene Mediated Cytotoxic Immunotherapy (GMCI™) to standard of care in patients with stage III/IV NSCLC that are not responding to a first line immune checkpoint inhibitor (ICI). GMCI kills tumor cells and creates an immune stimulatory environment in the tumor. Killing tumor cells in an immune stimulatory environment induces the body's immune system to detect and destroy cancer cells. Patients will receive two courses of GMCI with aglatimagene besadenovec injected into an accessible involved tumor site followed by 14 days of oral valacyclovir. Patients will continue with standard of care ICI, plus chemotherapy if indicated. The hypothesis is that the combination of GMCI and ICI may improve the response rate and overall clinical long-term benefit for NSCLC patients.

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

Detailed Description:

This trial seeks to add GMCI to stage III/IV NSCLC patients who are on standard of care first line ICI with evidence that the treatment may not be optimal but have the potential for delayed clinical benefit such that continuing the ICI is indicated. Studies of first line ICI have shown that most patients that will respond, respond in the first few weeks of treatment. However, a small percentage of patients have a delayed response with ICI. GMCI has been shown to increase the response rate to ICI in animal studies. Safety and potential efficacy of GMCI has been seen in clinical trials in over 700 patients with cancer (lung, pancreas, brain and ovarian). The goal of this study is to evaluate if adding GMCI can increase the percentage of patients that respond to the continued ICI. Patients may receive whatever standard of care therapy is indicated for their disease, such as maintenance chemotherapy, bevacizumab or focal radiation, in addition to continuing ICI. The eligibility criterion for determining that the ICI may not be working is based on time on ICI and response status with 3 cohorts as follows:

Cohort 1 is for patients with stable disease radiographically at least 18 weeks after starting ICI treatment and are clinically stable but appear to have disease that is not responding further.

Cohort 2 is for patients with evidence of radiographic progression at least 18 weeks after starting ICI treatment but who are clinically stable. Examples that would fit this cohort would be patients that have disease that decreased or was stable with initial ICI therapy, and then is slowly progressing or a new distant lesion appears on imaging, but the patient is otherwise clinically stable.

Cohort 3 is for patients who have new lesions or progression of existing lesions at least 9 weeks after starting ICI but who are clinically stable.

The specific ICI treatment regimen on this protocol is not specified to allow for different standard of care options with or without chemotherapy; for example, pembrolizumab alone, pembrolizumab plus chemotherapy, atezolizumab or atezolizumab plus 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 or cohort 3 if they develop a new lesion at 12 weeks after starting durvalumab.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 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 GMCI added to standard of care immune checkpoint inhibitor (ICI) therapy in stage III/IV NSCLC
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: GMCI Plus Standard of Care Immune Checkpoint Inhibitor for Stage III/IV NSCLC Patients
Actual Study Start Date : October 13, 2020
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine

Arm Intervention/treatment

Cohort 1 - persistent but stable disease at least 18 weeks after starting ICI treatment

Cohort 2 - 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

Biological: Aglatimagene besadenovec
Two courses of GMCI each involving aglatimagene besadenovec injection into an accessible involved tumor site followed by 14 days of oral valacyclovir. Patients will continue standard of care immune checkpoint inhibitor with or without chemotherapy.
Other Names:
  • AdV-tk
  • CAN-2409

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. Changes in quantity of CD8 T cell subsets [ Time Frame: 6 months ]
    Blood and tumor will be evaluated for changes in immune response before and after GMCI

  2. Overall Survival (OS) [ Time Frame: 3 years ]
    The OS curves will be estimated using the Kaplan-Meier method.

  3. Progression Free Survival (PFS) [ Time Frame: 3 years ]
    The PFS curves will be estimated using the Kaplan-Meier method.

  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 three 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, Cohort 2) have radiographic progressive disease at least 18 weeks after starting ICI treatment, or Cohort 3) have refractory disease defined as progressed by imaging at least 9 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 biopsy, 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 eligible and willing to continue ICI for at least the 12-week treatment period
  14. Patients must give study specific informed consent prior to enrollment and any study specific procedures

Exclusion Criteria:

  1. Patients with a history of severe hypersensitivity reaction to ICI
  2. Patients who require ongoing therapy with 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

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 identifier (NCT number): NCT04495153

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United States, Connecticut
UConn Health Recruiting
Farmington, Connecticut, United States, 06030
Contact: Quratulain (Annie) Ali    860-679-7648   
Principal Investigator: Omar Ibrahim, MD         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: John Ryan De Leon    773-702-4983   
Principal Investigator: Christine Bestvina, MD         
United States, Maryland
University of Maryland, Baltimore Recruiting
Baltimore, Maryland, United States, 21201
Contact: Maha Khalil    410-328-5009   
Principal Investigator: Ranee Mehra, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Travis Fisher    507-538-1960   
Contact: Karlyn Pierson   
Principal Investigator: Janani Reisenauer, MD         
United States, New York
NYU Langone Health Recruiting
New York, New York, United States, 10016
Contact: Yakira Pichardo    212-404-3682   
Contact: Alexa Brady    516-663-1215   
Principal Investigator: Daniel H. Sterman, MD FCCP, ATSF         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44106
Contact: Ellen Loftus    216-445-7290   
Principal Investigator: Pradnya Patil, MD         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Melissa Volpe    215-220-9703   
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   
Principal Investigator: Fabien Maldonado, MD         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Kaitlin Stephens    801-213-8494   
Principal Investigator: Wallace Akerley, MD         
United States, Virginia
Hunter Holmes McGuire VA Medical Center Recruiting
Richmond, Virginia, United States, 23249
Contact: Krista Chafin    804-675-5625   
Principal Investigator: Peter Lee, MD         
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: Melissa Schaefer    804-827-1025   
Principal Investigator: Erin Alesi, MD         
Sponsors and Collaborators
Candel Therapeutics, Inc.
NYU Langone Health
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Responsible Party: Candel Therapeutics, Inc. Identifier: NCT04495153    
Other Study ID Numbers: LuTK02
First Posted: July 31, 2020    Key Record Dates
Last Update Posted: March 29, 2022
Last Verified: March 2022

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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