Glioma Clinical Trials

• Histologically confirmed high grade (WHO Grade IV) glioma including but not limited to glioblastoma, gliosarcoma, glioblastoma with oligodendroglial features, glioblastoma with PNET features, tested as IDH wild-type, as per revised WHO 2021 criteria. Patients must also have evidence of tumor recurrence/progression by MRI (RANO criteria) after standard front-line therapy. b. First recurrence or progressive disease after a standard line therapy.

• Resectable disease: Resection is being considered as part of the standard of care for the patient and it is thought that it is feasible that a majority of contrast-enhancing tumor mass/signal can be resected.

• Patients must be between the ages of 18 and 75 years old (inclusive).

• Karnofsky Performance score ≥ 60.

• Use of steroids must be limited to ≤ 4 mg of decadron daily.

• Adequate organ function at time of screening visit including:

∙ Hgb ≥ 12 g/dL (male) or ≥ 11.5 g/dL (females)

‣ ANC ≥ 1500/uL

‣ Platelets ≥ 100,000/uL

‣ Absolute lymphocyte count ≥150/uL

‣ Serum Creatinine ≤ 1.5mg/dl; Cr clearance should be ≥ 50 mL/min

‣ Serum AST and ALT ≤ 3x ULN (Grade 1)

‣ Total Bilirubin ≤ 1.5 X ULN

‣ PT or PTT ≤ 1.25 X ULN

‣ Cardiac ejection fraction ≥45% without signs of physiologically significant pericardial effusion or clinically significant ECG findings.

∙ Baseline oxygen saturation \> 92% on room air

• Subjects of child-bearing or child-fathering potential must be willing to use an effective method of contraception (hormonal or two barrier methods) while on study and for at least 4 months following the last CAR T cell infusion or as long as B7-H3CART are detectable in peripheral blood or CSF.

• All female subjects of childbearing age must have a negative blood or urine pregnancy test.

• Ability to understand and willingness to sign a written informed consent document.

• Must be willing and able to comply with procedures, return visits and evaluations at Stanford Health Care while on this protocol.

• Prior Therapy:

‣ At least 6 weeks following completion of front-line radiation therapy.

⁃ At least 3 weeks post chemotherapy or 5 half-lives, whichever is shorter must have elapsed since any prior systemic therapy, except for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5 half-lives.

⁃ At least 4 weeks from bevacizumab treatment, which can be used only for radiation necrosis or pseudo-progression.

⁃ Prior cytotoxic chemotherapy, radiation, or other anticancer therapies including investigational agents discontinued at least 4 weeks prior to Day 1 of treatment.

⁃ Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities such as alopecia).