Clinical Trials /

EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults

NCT03618381

Description:

This is a phase I, open-label, non-randomized study that will enroll pediatric and young adult research participants with relapsed or refractory non-CNS solid tumors to evaluate the safety, feasibility, and efficacy of administering T cell products derived from the research participant's blood that have been genetically modified to express a EGFR-specific receptor (chimeric antigen receptor, or CAR) that will target and kill solid tumors that express EGFR and the selection-suicide marker EGFRt. EGFRt is a protein incorporated into the cell with our EGFR receptor which is used to identify the modified T cells and can be used as a tag that allows for elimination of the modified T cells if needed. On the first arm of the study, research participants will receive EGFR-specific CAR T cells only. On the second arm of the study, research participants will receive CAR T cells directed at EGFR and CD19, a marker on the surface of B lymphocytes, following the hypothesis that CD19+ B cells serving in their normal role as antigen presenting cells to T cells will promote the expansion and persistence of the CAR T cells. The CD19 receptor harbors a different selection-suicide marker, HERtG. The primary objectives of the study will be to determine the feasibility of manufacturing the cell products, the safety of the T cell product infusion, to determine the maximum tolerated dose of the CAR T cells products, to describe the full toxicity profile of each product, and determine the persistence of the modified cell in the subject's body on each arm. Subjects will receive a single dose of T cells comprised of two different subtypes of T cells (CD4 and CD8 T cells) felt to benefit one another once administered to the research participants for improved potential therapeutic effect. The secondary objectives of this protocol are to study the number of modified cells in the patients and the duration they continue to be at detectable levels. The investigators will also quantitate anti-tumor efficacy on each arm. Subjects who experience significant and potentially life-threatening toxicities (other than clinically manageable toxicities related to T cells working, called cytokine release syndrome) will receive infusions of cetuximab (an antibody commercially available that targets EGFRt) to assess the ability of the EGFRt on the T cells to be an effective suicide mechanism for the elimination of the transferred T cell products.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults
  • Official Title: Phase I Study of EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults

Clinical Trial IDs

  • ORG STUDY ID: STRIvE-01
  • NCT ID: NCT03618381

Conditions

  • Pediatric Solid Tumor

Interventions

DrugSynonymsArms
second generation 4-1BBζ EGFR806-EGFRtEGFR 806CAR(2G) -EGFRt
second generation 4-1BBζ EGFR806-EGFRt and a second generation 4 1BBζ CD19-Her2tGEGFR806CAR(2G)-EGFRt and CD19CAR(2G)-T2A-HER2tG

Purpose

This is a phase I, open-label, non-randomized study that will enroll pediatric and young adult research participants with relapsed or refractory non-CNS solid tumors to evaluate the safety, feasibility, and efficacy of administering T cell products derived from the research participant's blood that have been genetically modified to express a EGFR-specific receptor (chimeric antigen receptor, or CAR) that will target and kill solid tumors that express EGFR and the selection-suicide marker EGFRt. EGFRt is a protein incorporated into the cell with our EGFR receptor which is used to identify the modified T cells and can be used as a tag that allows for elimination of the modified T cells if needed. On the first arm of the study, research participants will receive EGFR-specific CAR T cells only. On the second arm of the study, research participants will receive CAR T cells directed at EGFR and CD19, a marker on the surface of B lymphocytes, following the hypothesis that CD19+ B cells serving in their normal role as antigen presenting cells to T cells will promote the expansion and persistence of the CAR T cells. The CD19 receptor harbors a different selection-suicide marker, HERtG. The primary objectives of the study will be to determine the feasibility of manufacturing the cell products, the safety of the T cell product infusion, to determine the maximum tolerated dose of the CAR T cells products, to describe the full toxicity profile of each product, and determine the persistence of the modified cell in the subject's body on each arm. Subjects will receive a single dose of T cells comprised of two different subtypes of T cells (CD4 and CD8 T cells) felt to benefit one another once administered to the research participants for improved potential therapeutic effect. The secondary objectives of this protocol are to study the number of modified cells in the patients and the duration they continue to be at detectable levels. The investigators will also quantitate anti-tumor efficacy on each arm. Subjects who experience significant and potentially life-threatening toxicities (other than clinically manageable toxicities related to T cells working, called cytokine release syndrome) will receive infusions of cetuximab (an antibody commercially available that targets EGFRt) to assess the ability of the EGFRt on the T cells to be an effective suicide mechanism for the elimination of the transferred T cell products.

Trial Arms

NameTypeDescriptionInterventions
EGFR 806CAR(2G) -EGFRtExperimentalAutologous CD4+ and CD8+ T cells that have been genetically modified to express the EGFR 806CAR(2G) -EGFRt
    EGFR806CAR(2G)-EGFRt and CD19CAR(2G)-T2A-HER2tGExperimentalAutologous CD4+ and CD8+ T cells that have been genetically modified to express the EGFR806CAR(2G)-EGFRt and CD19CAR(2G)-T2A-HER2tG

      Eligibility Criteria

              Inclusion Criteria:
      
                -  First 2 subjects enrolled and treated in both Arm A and Arm B: age ≥ 15 and ≤ 26 years
      
                -  Subsequent subjects: age ≥ 1 and ≤ 26 years
      
                -  Histologically diagnosed malignant, non-CNS solid tumor expressing EGFR
      
                -  Evidence of refractory or recurrent disease
      
                -  Able to tolerate apheresis
      
                -  Life expectancy ≥ 8 weeks
      
                -  Lansky or Karnofsky score ≥ 50
      
                -  Recovered from significant acute toxic effects of all prior chemotherapy,
                   immunotherapy, and radiotherapy
      
                -  ≥ 7 days post last chemotherapy/biologic therapy administration
      
                -  ≥ 3 half lives or 30 days, whichever is shorter, post last dose of anti-tumor antibody
                   therapy
      
                -  No prior virotherapy. Prior genetically modified cell therapy is allowed if not
                   detectable at enrollment.
      
                -  ≥ 6 weeks post last dose of myeloablative therapy and allogeneic or autologous stem
                   cell transplant
      
                -  ≥ 6 weeks post non-myeloablative therapy and allogeneic stem cell transplant
      
                -  Subjects who receive autologous stem cell infusion following non-myeloablative therapy
                   are eligible once all other eligibility requirements are met
      
                -  ≥ 7 days post last corticosteroid therapy
      
                -  Must not be receiving external beam radiation therapy at the time of study enrollment;
                   subjects with neuroblastoma must be ≥ 12 weeks from I131 MIBG therapy.
      
                -  Adequate organ function
      
                -  Adequate laboratory values
      
                -  Patients of childbearing potential must agree to use highly effective contraception
      
              Exclusion Criteria:
      
                -  Presence of active malignancy other than primary malignant solid tumor diagnosis
      
                -  Current relevant CNS pathology
      
                -  Presence of active GVHD, or receiving immunosuppressive therapy for treatment or
                   prevention of GVHD within 4 weeks prior to enrollment
      
                -  Presence of active severe infection
      
                -  Presence of primary immunodeficiency syndrome
      
                -  Receiving any anti-cancer agents or chemotherapy
      
                -  Pregnant or breastfeeding
      
                -  Unwilling or unable to provide consent/assent for participation in the study and 15
                   year follow up period
      
                -  Presence of any condition that, in the opinion of the investigator, would prohibit the
                   patient from undergoing treatment under this protocol
            
      Maximum Eligible Age:26 Years
      Minimum Eligible Age:1 Year
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Establish the safety, defined by adverse events, of EGFR806-specific CAR T cell infusions (Arm A), and of dual transduced EGFR806xCD19 CAR T cell infusions (Arm B)
      Time Frame:28 Days
      Safety Issue:
      Description:Type, frequency, severity, and duration of adverse events will be tabulated and summarized

      Secondary Outcome Measures

      Measure:Number of Arm A and Arm B subjects with persistence of CAR T cells in the peripheral blood at each visit time point
      Time Frame:84 Days
      Safety Issue:
      Description:Presence of CAR T cells in the peripheral blood will be assessed
      Measure:Number of Arm A and Arm B subjects with persistence of CAR T cells in the bone marrow at each visit time point
      Time Frame:84 days
      Safety Issue:
      Description:Presence of CAR T cells in the bone marrow will be assessed

      Details

      Phase:Phase 1
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Seattle Children's Hospital

      Trial Keywords

      • CAR T cell
      • Pediatric
      • Young Adults
      • Non-CNS solid tumor

      Last Updated