Clinical Trials /

GMCI Plus Standard of Care Immune Checkpoint Inhibitor for Stage III/IV NSCLC

NCT04495153

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: GMCI Plus Standard of Care Immune Checkpoint Inhibitor for Stage III/IV NSCLC
  • Official Title: GMCI Plus Standard of Care Immune Checkpoint Inhibitor for Stage III/IV NSCLC Patients

Clinical Trial IDs

  • ORG STUDY ID: LuTK02
  • NCT ID: NCT04495153

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
GMCIAdV-tk (aglatimagene besadenovec) + valacyclovirCohorts

Purpose

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.

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 650 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 at least 18 weeks after starting ICI treatment,
      thus they have radiographic stable disease and clinically are 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.
    

Trial Arms

NameTypeDescriptionInterventions
CohortsOtherCohort 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
  • GMCI

Eligibility Criteria

        Inclusion Criteria:

          1. Patients with Stage III/IV NSCLC on treatment with anti-PD-1/PD-L1 (ICI) +/-
             chemotherapy and a) have persistent but stable disease at least 18 weeks after
             starting ICI treatment, b) have radiographic progressive disease at least 18 weeks
             after starting ICI treatment, or c) have refractory disease defined as progressed by
             imaging at least 9 weeks after starting ICI treatment

          2. Measurable disease including a lesion that is amenable to injection

          3. Able and willing to undergo a pre-treatment and on-treatment biopsy

          4. ECOG Performance status of 0 or 1

          5. 18 years of age or older

          6. Granulocyte count (ANC) ≥ 1,000/mm3

          7. Peripheral lymphocyte count ≥ 500/mm3

          8. Hemoglobin ≥ 8 g/dl (patients may be transfused to meet this criterion)

          9. Platelets ≥ 75,000/mm3

         10. 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

         11. SGOT (AST) ≤ 5x upper limit of normal and if elevated, not clinically significant such
             that ICI can continue

         12. INR/aPTT within normal limits or, if on anti-coagulation, it must be clinically
             acceptable to hold anti-coagulation for the injection procedures as appropriate

         13. Serum creatinine < 2mg/dl and calculated creatinine clearance > 30ml/min

         14. Clinically eligible and willing to continue ICI

         15. Patients must give study specific informed consent prior to enrollment

        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 oxygen dependence (daily use)

         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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate
Time Frame:12 months
Safety Issue:
Description:Tumor response as measured by RECIST criteria

Secondary Outcome Measures

Measure:Changes in quantity of CD8 T cell subsets
Time Frame:6 months
Safety Issue:
Description:Blood and tumor will be evaluated for changes in immune response before and after GMCI
Measure:Overall Survival (OS)
Time Frame:3 years
Safety Issue:
Description:The OS curves will be estimated using the Kaplan-Meier method.
Measure:Progression Free Survival (PFS)
Time Frame:3 years
Safety Issue:
Description:The PFS curves will be estimated using the Kaplan-Meier method.
Measure:Changes in patient-reported symptoms using the NSCLC-SAQ
Time Frame:12 months
Safety Issue:
Description:NSCLC Symptoms Assessment Questionnaire (NSCLC-SAQ) score after compared to before treatment. Higher score indicates more severe symptoms.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Advantagene, Inc. d.b.a. Candel Therapeutics

Trial Keywords

  • Lung cancer
  • Immunotherapy
  • GMCI
  • AdV-tk
  • aglatimagene besadenovec

Last Updated

July 30, 2020