Multi-modular Chimeric Antigen Receptor T Cells tarGeting B7-H3 in Children, Teenage & Young Adult Sarcoma

Prior treatment

• Prior treatment with investigational or approved gene therapy or cell therapy products.
• Systemic corticosteroid therapy ≥ 0.05 mg/kg dexamethasone daily (or equivalent) at time of hBRCA84D CAR T cells infusion.
• Patients who have received any live vaccine in the six weeks prior to planned lymphodepletion
• Uncontrolled fungal, bacterial, viral, or other infection. Previously diagnosed infection for which the patient continues to receive antimicrobial therapy is permitted if responding to treatment and clinically stable at the time of scheduled hBRCA84D CAR T cell infusion.
• Systemic corticosteroid therapy ≥ 0.05 mg/kg dexamethasone daily (or equivalent) at time of hBRCA84D CAR T cell infusion.

Other illness

• Patients with only bone marrow detectable disease in the absence of measurable disease by cross sectional imaging.
• Patients with active, inoperative central nervous system (CNS) disease including leptomeningeal disease.
• Active hepatitis B, C or HIV infection.
• Clinically significant systemic illness or medical condition (e.g., significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of the investigational regimen and its requirements.
• Primary immunodeficiency or history of autoimmune disease (e.g., Crohn's, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression /systemic disease modifying agents within the last 2 years.

Lab values

• Known allergy to albumin, EDTA or DMSO.

Other

• Inability to tolerate leukapheresis.
• Any contraindication to lymphodepletion or to the use of Cyclophosphamide or Fludarabine as per the local SmPC.
• Any contraindication to the use of Anticoagulant Citrate Dextrose Solution.
• Life expectancy \<3 months.
• Women who are pregnant or breastfeeding.

• Age ≥ 1 and ≤ 24 years.
• Tissue diagnosis of RMS, ES or DSRCT
• Expression of B7-H3 in the tumour
• Relapsed or refractory disease after one or multiple lines of previous treatment.
• Measurable disease by cross sectional imaging. Patients with only bone marrow detectable disease (bone marrow aspirate or trephine) are NOT eligible for the study.
• At least 3 weeks or 5 half-lives, whichever is shorter, after treatment with agents on other early phase clinical trial.
• Performance status: Karnofsky (age ≥ 10 years) or Lansky (age \< 10) score ≥ 50%.
• Creatinine ≤1.5 x Upper Limit of Normal (ULN) for age, if higher, an estimated (calculated) creatinine clearance must be ≥ 60 ml/min/1.73 m2.
• Left ventricular ejection fraction (LVEF) ≥ 50%
• Absolute lymphocyte count ≥ 0.25 x 109/L.
• Women of childbearing potential (WOCBP) must have a negative pregnancy test and agree to comply with the pregnancy reporting requirements of the protocol (if applicable).
• Written informed consent.