An Open-label, First-in-human, Dose-escalation and Dose-expansion, Phase I Study of Fully Human B7H3/IL13Ra2 Bispecific Armored Chimeric Antigen Receptor T-Cell Therapy for Treatment of Recurrent or Refractory Glioblastoma
This study is an investigator-initiated, open-label Phase I clinical trial designed to evaluate the safety and efficacy of EPC-003 fully human anti-B7H3/IL13Ra2 armored Chimeric Antigen Receptor T-Cell Therapy (CAR-T) cell injection in patients with recurrent or refractory glioblastoma. Approximately 14 patients with relapsed or refractory glioblastoma are planned to be enrolled in this trial. During the screening period (Days -28 to -15), subjects will undergo relevant examinations or observations to confirm the disease status, treatment history, and other related information. Subjects who meet the screening criteria will be enrolled in the clinical trial to receive EPC-003 treatment. Specifically, they will receive intraventricular injection of EPC-003 via Ommaya reservoir on Day 0 (D0), Day 7 (D7), Day 14 (D14), Day 21 (D21), Day 28 (D28), and Day 35 (D35), once a week, totaling 6 administrations. All CAR-T cell infusions will be delivered via intraventricular injection. This trial comprises two phases: the first phase is the dose-escalation phase, and the second phase is the dose-expansion phase.
• 1: Agree to comply with the trial treatment plan and visit schedule, voluntarily enroll in the trial, and sign the informed consent form in writing.
• 2: On the day of signing the informed consent form, the subject shall be aged between 18 and 75 years inclusive, with no restriction on gender.
• 3: Karnofsky Performance Status (KPS) score ≥ 60%
• 4: Patients with B7H3- and/or IL13Ra2-positive recurrent or refractory glioblastoma confirmed by histopathology and/or cytology, meeting the following criteria: The positive expression rate of B7H3 \> 30%; The positive expression rate of IL13RA2 \> 30%; Disease progression or recurrence after standard treatment (postoperative radiotherapy combined with concurrent and adjuvant chemotherapy with temozolomide); The subject has at least one measurable lesion (based on RANO criteria, with mutually perpendicular diameters both ≥ 10mm).
• 5: Expected survival time ≥ 12 weeks;
• 6: Subjects must have adequate organ function, meeting the following laboratory test criteria: Bone Marrow Function: Absolute Neutrophil Count (ANC) ≥ 1.5×10⁹/L; Platelet Count (PLT) ≥ 100×10⁹/L; Absolute Lymphocyte Count ≥ 0.3×10⁹/L; Hemoglobin (HGB) ≥ 8.0 g/dL. Liver function: Serum total bilirubin (T-Bil) ≤ 1.5 × upper limit of normal (ULN); for patients without liver involvement, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN; for patients with liver involvement, ALT and AST ≤ 5 × ULN; Renal function: Serum creatinine ≤ 1.6 × ULN, or creatinine clearance (Ccr) ≥ 50 mL/min (calculated according to the Cockcroft-Gault formula); Coagulation function: International normalized ratio (INR) ≤ 1.5 × ULN; activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; Left ventricular ejection fraction \> 50%.
• 7: Male subjects with reproductive potential and female subjects of childbearing age must agree to use effective contraceptive measures from the time of signing the informed consent form until 1 year after the last administration of the trial drug. For female subjects of childbearing age, the pregnancy test result within ≤7 days before the administration of the trial drug must be negative.