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 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.
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
- Germ Cell Tumor
- Retinoblastoma
- Hepatoblastoma
- Wilms Tumor
- Rhabdoid Tumor
- Carcinoma
- Osteosarcoma
- Ewing Sarcoma
- Rhabdomyosarcoma
- Synovial Sarcoma
- Clear Cell Sarcoma
- Malignant Peripheral Nerve Sheath Tumors
- Desmoplastic Small Round Cell Tumor
- Soft Tissue Sarcoma
- Neuroblastoma
Interventions
| Drug | Synonyms | Arms |
|---|
| second generation 4-1BBζ EGFR806-EGFRt | | EGFR 806CAR(2G) -EGFRt |
| second generation 4-1BBζ EGFR806-EGFRt and a second generation 4 1BBζ CD19-Her2tG | | EGFR806CAR(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 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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| EGFR 806CAR(2G) -EGFRt | Experimental | Autologous CD4+ and CD8+ T cells that have been genetically modified to express the EGFR 806CAR(2G) -EGFRt | - second generation 4-1BBζ EGFR806-EGFRt
|
| EGFR806CAR(2G)-EGFRt and CD19CAR(2G)-T2A-HER2tG | Experimental | Autologous CD4+ and CD8+ T cells that have been genetically modified to express the EGFR806CAR(2G)-EGFRt and CD19CAR(2G)-T2A-HER2tG | - second generation 4-1BBζ EGFR806-EGFRt and a second generation 4 1BBζ CD19-Her2tG
|
Eligibility Criteria
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
| Maximum Eligible Age: | 30 Years |
| Minimum Eligible Age: | 1 Year |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Estimate the maximum tolerated dose (MTD) and dose limiting toxicities (DLT), and describe the full toxicity profile of the two CAR T cell products |
| 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
April 19, 2021
