Pilot Study of B7-H3 CAR-T in Treating Patients With Recurrent and Refractory Glioblastoma

Prior treatment

• Requirement for concurrent anticancer therapy during BP102 infusion.
• Expected need for systemic corticosteroids for glioblastoma within 3 months.
• History within the previous 6 months of any of the following cardiovascular conditions: New York Heart Association Class III or IV heart failure, coronary angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant heart disease.
• Clinically significant psychiatric illness, either prior to or at screening.
• Previous treatment with CAR-T cells or other genetically modified T-cell therapies.

Other illness

• History of another malignancy that has not been in remission for at least 2 years. The following are exempt from the 2-year requirement: non-melanoma skin cancer; completely resected Stage I tumors with a low risk of recurrence; treated localized prostate cancer; biopsy-confirmed cervical carcinoma in situ; or squamous intraepithelial lesions identified by a Pap smear.
• Active hepatitis B infection at screening, defined as hepatitis B virus DNA \>1,000 copies by PCR, or active hepatitis C or human immunodeficiency virus (HIV) infection.
• Uncontrolled systemic fungal, bacterial, viral, or other infection.
• Autoimmune disease.
• Any medical, psychological, family, social, or geographic condition that, in the investigator's judgment, could interfere with protocol compliance, or unwillingness or inability to comply with study procedures.

Other

• Participants meeting any of the following criteria will be excluded:
• Low adrenocorticotropic hormone (ACTH) and thyroid hormone levels.
• Pregnancy or breastfeeding.

• Participants must meet all of the following criteria:
• Age ≥18 years.
• Able and willing to provide written informed consent.
• Recurrent or refractory glioblastoma with measurable disease at enrollment.
• Glioblastoma confirmed by pathology, either from the current lesion or from the initial surgery, with pseudoprogression excluded by imaging. Available tumor tissue must be submitted for central laboratory analysis of B7-H3 expression.
• Intracranial tumor considered suitable for Ommaya reservoir implantation by the investigator.
• Karnofsky Performance Status (KPS) ≥70, confirmed before BP102 infusion.
• At least 6 weeks since completion of the last nitrosourea-based chemotherapy.
• At least 4 weeks since completion of the last temozolomide, other alkylating agent, other chemotherapy, or non-antiangiogenic targeted therapy. For participants whose most recent treatment was targeted therapy, screening may begin after a 2-week washout period if treatment-related adverse events have returned to baseline.
• At least 4 weeks since the last dose of the antiangiogenic drug anlotinib, with a negative fecal occult blood test.
• Adequate organ function, confirmed before BP102 infusion, as follows:
  • White blood cell count ≥2,000/μL; absolute neutrophil count ≥1,500/μL; platelet count ≥100 × 10³/μL; hemoglobin ≥9.0 g/dL.
  • Serum creatinine ≤1.5 × the upper limit of normal (ULN), or creatinine clearance \>30 mL/min/1.73 m² as calculated by the Cockcroft-Gault formula.
  • Alanine aminotransferase (ALT) ≤5 × ULN and total bilirubin \<2.0 mg/dL, or \<3.0 mg/dL in participants with Gilbert syndrome or hepatic involvement by glioblastoma.
  • Less than Grade 1 dyspnea according to the Common Terminology Criteria for Adverse Events (CTCAE), and oxygen saturation (SaO₂) ≥92% on room air.
  • Left ventricular ejection fraction (LVEF) ≥40%, assessed by echocardiography or multigated acquisition (MUGA) scan within 1 month before enrollment.
  • Normal coagulation function, including at least PT, APTT, and INR.
• Adequate vascular access for leukapheresis.
• Absolute peripheral blood lymphocyte count ≥0.5 × 10⁹/L without mobilization.
• Participants of childbearing potential must agree to use highly effective contraception for 1 year after BP102 infusion.
• Male participants with partners of childbearing potential must agree to use effective barrier contraception for 1 year after BP102 infusion.