GMCI Plus Standard of Care Immune Checkpoint Inhibitor for Stage III/IV NSCLC
Study Details
Study Description
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 |
|---|---|---|
|
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Cohorts 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:
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Outcome Measures
Primary Outcome Measures
- Response rate [12 months]
Tumor response as measured by RECIST criteria including overall response rate (ORR) and/or disease control rate (DCR)
- Safety graded by CTCAE version 5.0 [12 weeks]
Frequency of adverse events
Secondary Outcome Measures
- Changes in quantity of CD8 T cell subsets [6 months]
Blood and tumor will be evaluated for changes in immune response before and after GMCI
- Overall Survival (OS) [3 years]
The OS curves will be estimated using the Kaplan-Meier method.
- Progression Free Survival (PFS) [3 years]
The PFS curves will be estimated using the Kaplan-Meier method.
- Changes in patient-reported symptoms using the NSCLC-SAQ [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.
- Response rate [12 months]
Tumor Response as measured by iRECIST criteria
Eligibility Criteria
Criteria
Inclusion Criteria:
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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
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RECIST evaluable disease including a lesion that is amenable to injection
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Able and willing to undergo a pre-treatment and on-treatment biopsy, if feasible
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ECOG Performance status of 0 or 1
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18 years of age or older
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Granulocyte count (ANC) ≥ 1,000/mm3
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Hemoglobin ≥ 8 g/dl (patients may be transfused to meet this criterion)
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Platelets ≥ 75,000/mm3
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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
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SGOT (AST) ≤ 5x upper limit of normal and if elevated, not clinically significant such that ICI can continue
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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
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Serum creatinine < 2mg/dl and calculated creatinine clearance > 30ml/min
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Clinically eligible and willing to continue ICI for at least the 12-week treatment period
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Patients must give study specific informed consent prior to enrollment and any study specific procedures
Exclusion Criteria:
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Patients with a history of severe hypersensitivity reaction to ICI
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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
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Patients with a history of active autoimmune disease requiring treatment in the past 2 years
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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
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Women who are pregnant, lactating or intend to become pregnant during the study
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Patients who are known to be HIV positive
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Patients with a history of hypersensitivity or allergic reactions to valacyclovir or acyclovir
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Patients with significant heart disease (New York Heart Association Functional Classification III or IV)
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Patients with continuous oxygen dependence >2L/min at rest
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Tumor impinging on a neurovascular structure such that inflammation in the site may put patient at risk of compromise as determined by the investigator
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Patients with uncontrolled brain metastases as per investigator
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Patients with liver metastases involving more than half of the liver
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UConn Health | Farmington | Connecticut | United States | 06030 |
| 2 | University of Chicago | Chicago | Illinois | United States | 60637 |
| 3 | University of Maryland, Baltimore | Baltimore | Maryland | United States | 21201 |
| 4 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 5 | NYU Langone Health | New York | New York | United States | 10016 |
| 6 | Cleveland Clinic | Cleveland | Ohio | United States | 44106 |
| 7 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 8 | Vanderbilt University Medical Center | Nashville | Tennessee | United States | 37232 |
| 9 | University of Utah | Salt Lake City | Utah | United States | 84112 |
| 10 | Hunter Holmes McGuire VA Medical Center | Richmond | Virginia | United States | 23249 |
| 11 | Virginia Commonwealth University | Richmond | Virginia | United States | 23298 |
Sponsors and Collaborators
- Candel Therapeutics, Inc.
- NYU Langone Health
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- LuTK02