NCT07193628

B7H3/IL13Ra2 Bispecific Armored Chimeric Antigen Receptor T-Cell Therapy Study for Recurrent/Refractory Glioblastoma

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 14 (estimated)
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

This study is a dose-escalation and dose-expansion trial investigating the safety and efficacy of B7H3/IL13Ra2 bispecific CAR-T cell preparation in patients with recurrent or refractory glioma. 1. Dose-escalation phase Four dose groups are set in the dose-escalation phase: 2.5×10⁶, 5×10⁶, 10×10⁶, and 20×10⁶ cells per infusion, administered once weekly for a total of 6 doses. Dose escalation will be implemented through a combination of accelerated titration and 3+3 design. The accelerated titration design will be applied to the first 3 dose levels (with only 1 subject enrolled per level): If dose-limiting toxicity (DLT) or two grade ≥2 drug-related adverse events (AEs) are observed at any accelerated titration dose level, the current dose level will be expanded to 3 subjects, and subsequent trials will automatically switch to the 3+3 design. When 2 out of 3 subjects in a dose group experience DLT, dose escalation will be terminated, and this dose level will be identified as the non-tolerated dose. The previous dose level will then be expanded to 3 subjects. During the dose-escalation process, cell infusion for the first subject in the subsequent dose group can only be performed after the last subject in the previous dose group completes the 28-day DLT observation period. Within the same dose group, cell infusion for the second subject may start after the first subject completes the 2-week preliminary safety observation. The third subject will initiate cell infusion after the second subject finishes the 2-week safety observation. 2. Dose-expansion phase The dose-expansion phase will commence enrollment after preliminary safety, tolerability, and efficacy results are obtained from the dose-escalation phase. Six patients will be enrolled at the highest tolerable dose level below the non-tolerated dose to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D). MTD is defined as the highest tolerable dose with DLT observed in ≤1/6 subjects. RP2D will be determined based on the review of safety and efficacy data collected from the dose-escalation and dose-expansion cohorts. During the trial, if necessary and with consensus, the CAR-T cell infusion schedule may be adjusted from once weekly to once every two weeks, or the dose and dose levels may be reduced.

Conditions

• Refractory Glioblastoma
• Recurrent Glioblastoma

Interventions

Type	Name	Description
BIOLOGICAL	EPC-003 Fully Human Anti-B7H3/IL13Ra2 Armored CAR-T Cell Therapy (Dose level 1)	2.5 × 10⁶ EPC-003 CAR-T cells will be administered into the Ommaya reservoir of the subjects weekly.
BIOLOGICAL	EPC-003 Fully Human Anti-B7H3/IL13Ra2 Armored CAR-T Cell Therapy (Dose level 2)	5 × 10⁶ EPC-003 CAR-T cells will be administered into the Ommaya reservoir of the subjects weekly.
BIOLOGICAL	EPC-003 Fully Human Anti-B7H3/IL13Ra2 Armored CAR-T Cell Therapy (Dose level 3)	10 × 10⁶ EPC-003 CAR-T cells will be administered into the Ommaya reservoir of the subjects weekly.
BIOLOGICAL	EPC-003 Fully Human Anti-B7H3/IL13Ra2 Armored CAR-T Cell Therapy (Dose level 4)	20 × 10⁶ EPC-003 CAR-T cells will be administered into the Ommaya reservoir of the subjects weekly.

Timeline

• Start date: 2025-09-26
• Primary completion: 2027-12-31
• Completion: 2028-12-31
• First posted: 2025-09-26
• Last updated: 2025-11-18

Locations

1 site across 1 country: China