Tests a B7-H3 targeted T-cell therapy in children with solid tumors

Trial details

Who runs it

St. Jude Children's Research Hospital

Trial code

NCT04897321

Record updated

19 May 2026

Original description

3CAR is being done to investigate an immunotherapy for patients with solid tumors. It is a Phase I clinical trial evaluating the use of autologous T cells genetically engineered to express B7-H3-CARs for patients ≤ 21 years old, with relapsed/refractory B7-H3+ solid tumors. This study will evaluate the safety and maximum tolerated dose of B7-H3-CAR T cells.The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give to patients with B7-H3-positive solid tumors.Read full original descriptionShow less

B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)

3CAR is being done to investigate an immunotherapy for patients with solid tumors. It is a Phase I clinical trial evaluating the use of autologous T cells genetically engineered to express B7-H3-CARs for patients ≤ 21 years old, with relapsed/refractory B7-H3+ solid tumors. This study will evaluate the safety and maximum tolerated dose of B7-H3-CAR T cells.The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give to patients with B7-H3-positive solid tumors.

Primary objective

To determine the safety of one intravenous infusion of autologous, B7-H3-CAR T cells in patients (≤ 21 years) with recurrent/refractory B7-H3+ solid tumors after lymphodepleting chemotherapy

Secondary objective

To evaluate the antitumor activity of B7-H3-CAR T cells

Exploratory objectives

* To evaluate the tumor environment after treatment with B7-H3-CAR T cells * To assess the immunophenotype, clonal structure and endogenous repertoire of B7-H3-CAR T cells and unmodified T cells * To characterize the cytokine profile in the peripheral blood after treatment with B7-H3-CAR T cells

Inclusion: Procurement and T-cell production eligibility*; *a previously collected, autologous leukapheresis product can be used for T-cell production; Age ≤21 years old; B7-H3+ solid tumor with measurable disease; B7-H3 expression will be evaluated by standard immunohistochemistry (IHC) using a previously obtained biopsy; a tumor is considered B7-H3 positive with an H-score ≥100; Estimated life expectancy of >12 weeks; Karnofsky or Lansky (age-dependent) performance score ≥50; For females of child bearing age:; Not pregnant with negative serum pregnancy test within 7 days prior to enrollment; Not lactating with intent to breastfeed; Meets eligibility criteria to undergo autologous apheresis, or have previously undergone autologous apheresis; Treatment eligibility; Age ≤21 years old; B7-H3+ solid tumor with measurable disease; Evidence of relapsed or refractory disease after standard first-line therapy; Estimated life expectancy of >8 weeks; Karnofsky or Lansky (age-dependent) performance score≥50; Echocardiogram with a ventricular ejection fraction; >40%; or shortening fraction ≥25%; Adequate renal function defined as creatinine clearance or radioisotope GFR 50 ml/min/1.73m2 (GFR 40 ml/min/1.73m2 if < 2 years of age); Adequate pulmonary function defined as pulse oximetry ≥92% on room air or forced vital capacity (FVC) ≥50% of predicted value; Total Bilirubin ≤3 times the upper limit of normal for age, except in subjects with Gilbert's syndrome; Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤5 times the upper limit of normal for age; Hemoglobin≥ 7g/dL (can be transfused); Platelet count >50,000/uL (can be transfused); Absolute neutrophil count (ANC) ≥ 1000/uL; Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy; For females of child bearing age:; Not pregnant with negative serum pregnancy test within 7 days prior to enrollment; Not lactating with intent to breastfeed; If sexually active, agreement to use birth control until 3 months after T-cell infusion. Male partners should use a condom; Available autologous transduced T-cell product that has met GMP release criteria; Agreement to participate in long-term follow-up protocol for patients, who have received genetically modified cell products.

Exclusion: Receiving systemic steroid therapy exceeding the equivalent of 0.5 mg/kg/day of methylprednisolone, in the 7 days prior to B7-H3-CAR T-cell infusion; Receiving systemic therapy in the 14 days prior to CAR T-cell infusion, which will interfere with the activity of the B7-H3-CAR product (in the opinion of the study PIs); Known HIV positivity; Severe intercurrent bacterial, viral or fungal infection (e.g. active hepatitis B or C infection or adenovirus infection); History of hypersensitivity reactions to murine protein-containing products; Rapidly progressive disease (in the opinion of the study PIs); History of HIV infection; Severe, uncontrolled intercurrent bacterial, viral or fungal infection; History of hypersensitivity reactions to murine protein-containing products; Rapidly progressing disease (in the opinion of the study PIs); Known primary immunodeficiency; Known primary immunodeficiency.

ClinicalTrials.gov NCT04897321