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

April 6, 2024 updated by: Colleen Annesley, Seattle Children's Hospital

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

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 Arm A of the study, research participants will receive EGFR-specific CAR T cells only. On Arm B 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) or trastuzumab (an antibody commercially available that targets HER2tG) 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

44

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98105
        • Recruiting
        • Seattle Children's Hospital
        • Contact:
          • Katie Albert, MD
        • Principal Investigator:
          • Katie Albert, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 30 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • First 2 subjects enrolled and treated in both Arm A and Arm B: age ≥ 15 and ≤ 30 years
  • Subsequent subjects: age ≥ 1 and ≤30years
  • Histologically diagnosed malignant, non-CNS solid tumor expressing EGFR
  • Evidence of refractory or recurrent disease
  • Able to tolerate apheresis or has apheresis product available for use in manufacturing
  • Life expectancy ≥ 8 weeks
  • Lansky or Karnofsky score ≥ 50
  • Recovered from significant acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy
  • If no apheresis product or T cell product is available,≥ 7 days post last chemotherapy/biologic therapy administration
  • If no apheresis product or T cell product is available,≥ 3 half lives or 30 days, whichever is shorter, post last dose of anti-tumor antibody therapy (including check point inhibitor)
  • Prior genetically modified cell therapy is allowed if not detectable at enrollment.
  • If no apheresis product or T cell product is available,≥ 6 weeks post last dose of myeloablative therapy and allogeneic or autologous stem cell transplant
  • Subjects who receive autologous stem cell infusion following non-myeloablative therapy are eligible once all other eligibility requirements are met
  • If no apheresis product or T cell product is available,≥ 7 days post last systemic corticosteroid therapy (physiologic replacement dosing is allowed)
  • If no apheresis product or T cell product is available, 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 external beam radiation therapy at time of enrollment
  • Receiving any anti-cancer agents or chemotherapy
  • Pregnant or breastfeeding
  • Unwilling 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: EGFR 806CAR(2G) -EGFRt
Autologous CD4+ and CD8+ T cells that have been genetically modified to express the EGFR 806CAR(2G) -EGFRt
Biological: second generation 4-1BBζ EGFR806-EGFRt
Autologous CD4 and CD8 T cells lentivirally transduced to express a second generation 4-1BBζ EGFR806-EGFRt
Experimental: EGFR806CAR(2G)-EGFRt and CD19CAR(2G)-T2A-HER2tG
Autologous CD4+ and CD8+ T cells that have been genetically modified to express the EGFR806CAR(2G)-EGFRt and CD19CAR(2G)-T2A-HER2tG
Biological: second generation 4-1BBζ EGFR806-EGFRt and a second generation 4 1BBζ CD19-Her2tG
Autologous CD4 and CD8 T cells lentivirally transduced to express a second generation 4-1BBζ EGFR806-EGFRt and a second generation 4 1BBζ CD19-Her2tG

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The number of successfully manufactured EGFR806 and EGFR806xCD19 CAR T cell products will be assessed
Time Frame: 28 Days
The number of successfully manufactured products will be measured
28 Days
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
Type, frequency, severity, and duration of adverse events will be tabulated and summarized
28 Days
Estimate the maximum tolerated dose (MTD) or biologically effective dose and dose limiting toxicities (DLT), and describe the full toxicity profile of the two CAR T cell products
Time Frame: 28 days
Type, frequency, severity, and duration of adverse events will be tabulated and summarized
28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Presence of CAR T cells in the peripheral blood will be assessed
84 Days
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
Presence of CAR T cells in the bone marrow will be assessed
84 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
To quantitate anti-tumor responses by measuring changes in tumor burden using disease-specific evaluations and describe survival characteristics following CAR T cell infusion
Time Frame: 84 Days
Standard imaging and bone marrow pathology will be used to determine disease response
84 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seattle Children's Hospital

Investigators

  • Study Chair: Katie Albert, MD, Seattle Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 18, 2019

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

June 1, 2040

Study Registration Dates

First Submitted

July 16, 2018

First Submitted That Met QC Criteria

August 6, 2018

First Posted (Actual)

August 7, 2018

Study Record Updates

Last Update Posted (Actual)

April 9, 2024

Last Update Submitted That Met QC Criteria

April 6, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STRIvE-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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