A Phase 1 interventional study of second generation 4-1BBζ B7H3-EGFRt-DHFR and second generation 4-1BBζ B7H3-EGFRt-DHFR(selected) and a second generation 4-1BBζ CD19-Her2tG in Pediatric Solid Tumor, Germ Cell Tumor and Retinoblastoma, sponsored by Seattle Children's Hospital. Active, not recruiting at 1 site in United States. Open to participants aged 0 Years to 26 Years. Per ClinicalTrials.gov, last updated 2026-04-28.
Sponsored by Seattle Children's Hospital · Phase 1, Interventional, and Treatment
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 B7H3-specific receptor (chimeric antigen receptor, or CAR) that will target and kill solid tumors that express B7H3. On Arm A of the study, research participants will receive B7H3-specific CAR T cells only. On Arm B of the study, research participants will receive CAR T cells directed at B7H3 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. Arm A CAR T cells include the protein EGFRt and Arm B CAR T cells include the protein HER2tG. These proteins can be used to both track and destroy the CAR T cells in case of undue toxicity. 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 participant's body on each arm. Participants 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. Participants 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.
166 studies on the registry are indexed under Neoplasms, Germ Cell and Embryonal; 48 are open to participants now.
This study's planned enrollment of 68 is above the median of 36 across 124 interventional studies indexed under Neoplasms, Germ Cell and Embryonal.
Browse Neoplasms, Germ Cell and Embryonal studies →Seattle Children's Hospital is the lead sponsor of 215 studies on the registry; 44 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
PD-1, PD-L1 and checkpoint inhibitors
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GVHD (graft-versus-host disease)
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autologous CD4+ and CD8+ T-cells genetically modified to express an B7H3-specific CAR
Biological: second generation 4-1BBζ B7H3-EGFRt-DHFR
Autologous CD4+ and CD8+ T-cells genetically modified to a bispecific B7H3xCD19 CAR
Biological: second generation 4-1BBζ B7H3-EGFRt-DHFR(selected) and a second generation 4-1BBζ CD19-Her2tG
Autologous CD4+ and CD8+ T-cells genetically modified to express a bispecific B7H3xCD19 CAR given in combination with pembrolizumab
Biological: second generation 4-1BBζ B7H3-EGFRt-DHFR(selected) and a second generation 4-1BBζ CD19-Her2tG · Drug: Pembrolizumab
Autologous CD4+ and CD8+ T-cells lentivirally transduced to express a second generation 4-1BBζ B7H3-EGFRt-DHFR
Autologous CD4+ and CD8+ T-cells lentivirally transduced to express a second generation 4-1BBζ B7H3-EGFRt-DHFR(selected) and a second generation 4-1BBζ CD19-Her2tG
SCRI-CARB7H3(s)x19 plus pembrolizumab
Assess the safety and tolerability of cellular immunotherapy utilizing ex-vivo expanded autologous T cells genetically modified to express B7H3-specific CAR (Arm A)
Type, frequency, severity, and duration of adverse events will be tabulated and summarized
Time frame: 28 days
Assess the safety and tolerability of cellular immunotherapy utilizing ex-vivo expanded autologous T cells genetically modified to express a bispecific B7H3xCD19 CAR (Arm B)
Type, frequency, severity, and duration of adverse events will be tabulated and summarized
Time frame: 28 days
To assess the safety and tolerability of cellular immunotherapy utilizing ex-vivo expanded autologous T cells genetically modified to express a bispecific B7H3xCD19 CAR given in combination with pembrolizumab (Arm C)
Type, frequency, severity, and duration of adverse events will be tabulated and summarized to determine maximal tolerated dose
Time frame: 28 days
To determine the maximum tolerated dose (MTD) of B7H3-specific CAR (Arm A)
Type, frequency, severity, and duration of adverse events will be tabulated and summarized to determine maximal tolerated dose
Time frame: 28 days
To determine the maximum tolerated dose of bispecific B7H3xCD19 CAR (Arm B)
Type, frequency, severity, and duration of adverse events will be tabulated and summarized
Time frame: 28 days
To determine the feasibility of administration of pembrolizumab in combination with bispecific B7H3xCD19 CAR (Arm C)
Type, frequency, severity, and duration of adverse events will be tabulated and summarized
Time frame: 28 days
To assess the dose limiting toxicities (DLTs) and describe the full toxicity profile for each study arm
Type, frequency, severity, and duration of adverse events will be tabulated and summarized
Time frame: 28 days
To assess the feasibility of manufacturing B7H3 specific CARs from patient-derived lymphocytes
Type, frequency, severity, and duration of adverse events will be tabulated and summarized
Time frame: 28 days
To assess the feasibility of manufacturing B7H3xCD19 bispecific CARs from patient-derived lymphocytes
Type, frequency, severity, and duration of adverse events will be tabulated and summarized
Time frame: 28 days
Determine the duration of in vivo persistence of adoptively transferred T cells in the peripheral blood and compare engraftment between T cell products and treatment arms
Presence of CAR T cells in the peripheral blood will be assessed
Time frame: 84 days
Determine the magnitude of in vivo persistence of adoptively transferred T cells in the peripheral blood and compare engraftment between T cell products
Number of CAR T cells in the peripheral blood will be assessed
Time frame: 84 days
Quantitate anti-tumor responses by measuring changes in tumor burden using disease-specific evaluations
Presence of CAR T cells in the peripheral blood will be assessed
Time frame: 84 days
Describe the relative expansion and persistence of the CAR T cell product and retention of function for B7H3xCD19 bispecific CARs determined by maintenance of B cell aplasia (BCA) with and without pembrolizumab
Presence of CAR T cells in the peripheral blood will be assessed
Time frame: 84 days
Evaluate for the presence of B7H3 CAR T cells in tumor tissue and/or normal tissue if a tissue biopsy, tumor biopsy, or resection is clinically indicated post-treatment
Tumor tissue, when obtained, will be assessed for the presence of adoptively transferred CAR T cells
Time frame: 84 days
Evaluate B7H3 antigen expression in tumor tissue and/or normal tissue if a tissue biopsy, tumor biopsy, or resection is available
Tumor tissue, when obtained, will be assessed for the presence of B7H3 antigen
Time frame: 84 days
Analyze blood, bone marrow, CSF, normal tissue, and/or tumor tissue for biomarkers of safety and/or anti-tumor activity
If a tissue biopsy, tumor biopsy, or resection is clinically indicated post-treatment, pathology will be assessed for the presence of B7H3 CAR T cells
Time frame: 84 days
Assess the efficacy of infusional cetuximab and/or trastuzumab in ablating transferred T cells and ameliorating acute toxicities in treated participants
Biologic specimens, when obtained, will be assessed for biomarkers of safety and/or anti-tumor efficacy
Time frame: 84 days
Plan to share: No
This study is active, not recruiting, as verified in Nov 2025. You cannot join it, but the record below documents what was studied.
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