B7H3 CAR T Cell Immunotherapy for the Treatment of Children and Young Adults with Recurrent or Refractory Solid Tumors

Inclusion Criteria

• Subjects age =< 26 years at the time of consent for study participation; the first 2 subjects enrolled and treated with CAR T cells in both Arms A and B will be >= 15 years and =< 26 years at time of consent for study participation
• Histologically diagnosed malignant, non-primary central nervous system (CNS) solid tumor
• Evidence of refractory or recurrent disease, as defined below, for which there is no known curative therapy: * Solid tumors, except neuroblastoma (any of the following): ** New site of measurable disease by radiographic imaging (including fludeoxyglucose F 18-positron emission tomography [FDG-PET]) or histologic confirmation ** Greater than 20% increase in at least one tumor dimension documented by computed tomography (CT)/magnetic resonance imaging (MRI), AND a minimum absolute increase of 5 mm in longest dimension of existing lesion(s). Previously irradiated lesions may be included ** New bone marrow disease with infiltration of > 5% tumor cells ** Persistent measurable disease or FDG-PET avid bone metastasis that has failed to achieve complete remission to upfront conventional therapy (surgery, radiotherapy, and/or chemotherapy) and standard salvage therapy * Neuroblastoma (any of the following): ** New disease site documented on iodine-123 metaiodobenzylguanidine (I-123 MIBG) or CT/MRI OR any new bone site that is FDG-PET avid (in subject known to have MIBG non-avid tumor), AND has MRI findings consistent with tumor OR has a biopsy of any lesion showing neuroblastoma (NB) or ganglioneuroblastoma ** Greater than 20% increase in a least one dimension of soft tissue mass documented by CT/MRI AND a minimum absolute increase of 5 mm in longest dimension in existing lesion(s). Previously irradiated lesions may be included ** Bone marrow biopsy meeting revised International Neuroblastoma Response Criteria for progressive disease ** Stable persistent disease, such that response at the completion of upfront therapy or salvage therapy is less than partial response AND has a biopsy of at least one site showing viable solid tumor consistent with initial diagnosis ** Responding persistent disease, defined as at least a partial response to frontline therapy (i.e. subject has had at least a partial response to frontline therapy but still has residual disease by MIBG scan, CT/MRI, or bone marrow aspirate/biopsies). Subjects in this category are required to have histologic confirmation of viable NB from at least one residual site (tumor seen on routine bone marrow morphology is sufficient)
• Lansky or Karnofsky score >= 50. Subjects who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for purposes of assessing performance status
• Life expectancy >= 8 weeks
• Subject has fully recovered from significant acute toxic effects of all prior chemotherapy, immunotherapy and radiotherapy
• All chemotherapy has been discontinued >= 7 days prior to enrollment (this does not apply to subjects with apheresis product or usable T cell product available for use in STRIvE-02)
• All biologic therapy has been discontinued >= 7 days prior to enrollment (this does not apply to subjects with apheresis product or usable T cell product available for use in STRIvE-02)
• All systemic corticosteroid therapy has been discontinued >= 7 days prior to enrollment (this does not apply to subjects with apheresis product or usable T cell product available for use in STRIvE-02). Glucocorticosteroid physiologic replacement therapy for management of adrenal insufficiency and/or topical administration (e.g. inhaled or dermatologic) is allowed
• Subject is at least 3 half-lives or 30 days (whichever is shorter) from time of last dose of antitumor directed antibody therapy (including check point inhibitor) at time of enrollment. This does not apply to subjects with apheresis product or usable T cell product available for use in STRIvE02
• At time of enrollment, subject is at least 6 weeks from myeloablative therapy and autologous and/or allogeneic stem cell transplant, or non-myeloablative therapy and allogeneic stem cell transplant (all timed from stem cell infusion). Subjects who received an autologous stem cell infusion following non-myeloablative therapy do not have a wash-out period, they are eligible once they meet all other eligibility requirements. This criterion does not apply to subjects with apheresis product or usable T cell product available for use in STRIvE-02
• In subjects who have received genetically modified cell therapy, it must be at least 30 days from most recent cell infusion prior to enrollment. This criterion does not apply to subjects with apheresis product or usable T cell product available for use in STRIvE-02
• Neuroblastoma subjects only: at time of enrollment, subject is at least 12 weeks from prior I-131 MIBG therapy (this does not apply to subjects with apheresis product or usable T cell product available for use in STRIvE-02)
• Serum creatinine =< upper limit of normal values based on serum creatinine upper limit of normal values: * Age (in years): Serum creatinine upper limit of normal (ULN) (in mg/dL) ** 1 to < 2: 0.6 (male), 0.6 (female) ** 2 to < 6: 0.8 (male), 0.8 (female) ** 6 to < 10: 1.0 (male), 1.0 (female) ** 10 to < 13: 1.2 (male), 1.2 (female) ** 13 to < 16: 1.5 (male), 1.4 (female) ** >= 16: 1.7 (male), 1.4 (female)
• Total bilirubin =< 3 x upper limit of normal (ULN) for age OR direct bilirubin =< 2 mg/dL
• Alanine transferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 x ULN AND aspartate aminotransferase (AST) =< 5 x ULN
• Shortening fraction >= 28% or an ejection fraction >= 50% by echocardiogram (ECHO)
• Absolute lymphocyte count (ALC) >= 100 cells/uL (this does not apply to subjects with apheresis product or usable T cell product available for use in STRIvE-02)
• Absolute neutrophil count (ANC) >= 1000 cells/uL
• Hemoglobin >= 8 g/dL (subjects receiving blood product transfusions are acceptable as long as they are not determined to be transfusion refractory)
• Platelet count >= 100,000/uL (subjects receiving blood product transfusions are acceptable as long as they are not determined to be transfusion refractory)
• Negative human immunodeficiency virus (HIV) antigen and antibody (within 3 months prior to enrollment), AND
• Negative hepatitis B surface antigen (within 3 weeks prior to enrollment), AND
• Negative hepatitis C antibody (within 3 weeks prior to enrollment) (if hepatitis C antibody is positive, subject must have a subsequent negative hepatitis C quantitative polymerase chain reaction [qPCR])
• Oxygen saturation >= 90% on room air without supplemental oxygen or ventilation and no dyspnea at rest
• Subject is able to tolerate apheresis (including placement of temporary apheresis catheter, if necessary), or already has an apheresis product available for use in manufacturing
• Subjects of child-bearing potential or capable of fathering a child must agree to use highly effective contraception from time of initial CAR T cell administration through 12 months following the final administration of investigational product

Exclusion Criteria

• Subject has an active malignancy (including primary CNS malignancy) other than primary malignant solid tumor diagnosis (CNS intracranial metastases are allowed)
• Subject has ongoing, symptomatic CNS pathology requiring medical intervention, including paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injury, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder. Subjects with non-febrile seizure disorder controlled on anti-epileptic medication and without seizure within 3 months are eligible for enrollment
• Receiving external beam radiation therapy (there is no wash-out period, however subjects may not be receiving therapy at the time of enrollment)
• Subjects with history of allogeneic hematopoietic stem cell transplant only: active graft versus host disease (GVHD), or receiving immunosuppressive therapy for treatment or prevention of GVHD within 4 weeks prior to enrollment
• Subject is pregnant or breastfeeding
• Subject has presence of active severe infection, defined as: * Positive blood culture within 48 hours of enrollment, AND/OR * Fever > 38.2 degrees Celsius (C ) AND clinical signs of infection within 48 hours of enrollment
• Subject has presence of any condition that, in the option of an investigator, would prohibit the subject from undergoing treatment under this protocol
• Subject has primary immunodeficiency
• Subject and/or authorized legal representative are unwilling to provide consent/assent for study participation including participation in the 15 year follow up period that is required if CAR T cell therapy is administered