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

Inclusion Criteria:

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 bystandard immunohistochemistry (IHC) using a previously obtained biopsy; a tumor isconsidered 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 previouslyundergone autologous apheresis

Exclusion Criteria:

• Known primary immunodeficiency

• Known HIV positivity

• Severe intercurrent bacterial, viral or fungal infection (e.g. active hepatitis B orC infection or adenovirus infection)

• History of hypersensitivity reactions to murine protein-containing products

• Rapidly progressive disease (in the opinion of the study PIs)

Inclusion criteria

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 50ml/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 forcedvital capacity (FVC) ≥50% of predicted value

• Total Bilirubin ≤3 times the upper limit of normal for age, except in subjects withGilbert's syndrome

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤5 times theupper 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 fromprior 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-cellinfusion. 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 havereceived genetically modified cell products

Exclusion criteria

• Known primary immunodeficiency

• History of HIV infection

• Severe, uncontrolled intercurrent bacterial, viral or fungal infection

• History of hypersensitivity reactions to murine protein-containing products

• Receiving systemic steroid therapy exceeding the equivalent of 0.5 mg/kg/day ofmethylprednisolone, 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 willinterfere with the activity of the B7-H3-CAR product (in the opinion of the studyPIs).

• Rapidly progressing disease (in the opinion of the study PIs)