Recurrent GlioblastomaPhase 1NCT04385173
Pilot Study of B7-H3 CAR-T in Treating Patients With Recurrent and Refractory Glioblastoma
A Phase 1 study testing BP102 (B7-H3 CAR-T) in people with Recurrent Glioblastoma and Refractory Glioblastoma, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial summary
This is a pilot phase I, single-center, open-label, single-arm study to evaluate the feasibility, safety, tolerability, and preliminary efficacy of repeated intracranial infusions of BP102 in adults with recurrent or refractory glioblastoma. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Recurrent Glioblastoma, Refractory Glioblastoma
- What is being tested?
- BP102 (B7-H3 CAR-T)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2022to 1 Sep 2026
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- Participants meeting any of the following criteria will be excluded:
- 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.
- Requirement for concurrent anticancer therapy during BP102 infusion.
- Expected need for systemic corticosteroids for glioblastoma within 3 months.
- 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.
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- 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.
- Low adrenocorticotropic hormone (ACTH) and thyroid hormone levels.
- Autoimmune disease.
- Pregnancy or breastfeeding.
- 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.
- Previous treatment with CAR-T cells or other genetically modified T-cell therapies.
Trial locations and contacts
1 site in 1 country.
China1 site
the Second Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310009
About this study
Official title: A Pilot Study of Chimeric Antigen Receptor (CAR) T Cells Targeting B7-H3 Antigen in Treating Patients With Recurrent and Refractory Glioblastoma
This is a pilot phase I, single-center, open-label, single-arm study to evaluate the feasibility, safety, tolerability, and preliminary efficacy of repeated intracranial infusions of BP102 in adults with recurrent or refractory glioblastoma. BP102 is an investigational autologous B7-H3 CAR-T cell therapy manufactured from each patient's peripheral blood mononuclear cells. B7-H3 CAR-T cells are designed to recognize B7-H3 expressed on glioblastoma cells. BP102 will be administered into the tumor cavity or cerebral ventricle through an implanted Ommaya reservoir. The study will also evaluate pharmacokinetic and pharmacodynamic characteristics, progression-free survival, and overall survival.
Read the detailed description
Background
- B7-H3 is expressed in 70% of patients with glioblastoma
- B7-H3 is not expressed in normal tissues especially not in central nervous system. Therefore, it is an attractive GBM target for CAR-T therapy
- The investigators constructed a retroviral vector encoding a chimeric antigen receptor (CAR) targeting B7-H3, which can mediate CAR transfer into patient T cells with high efficiency.
Objectives
- Primary Objective: To evaluate the feasibility, safety, and tolerability of intracranially administered BP102 in adult subjects with recurrent/refractory (R/R) glioblastoma (GBM).
- Secondary Objectives:
- To characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of BP102.
- To assess the antitumor activity of BP102, including objective response rate (ORR) and duration of response.
- To evaluate progression-free survival (PFS) and overall survival (OS) among subjects receiving BP102 treatment.
- Exploratory Objective:
- To evaluate the impacts of tumor and tumor microenvironment on the pharmacokinetics and pharmacodynamics of BP102.
Design This is a single-center, open-label, single-arm, pilot phase I study enrolling approximately 12 adults with recurrent or refractory glioblastoma. Participants will undergo leukapheresis and Ommaya reservoir implantation, followed by three planned intracranial infusions of autologous BP102 B7-H3 CAR-T cells at approximately 1- to 2-week intervals. Dose escalation will follow the protocol-defined intra-participant and inter-participant 3+3 rules, based on safety and dose-limiting toxicities. Participants who respond to BP102 may receive additional treatment cycles based on the investigator's risk-benefit assessment. Safety, antitumor activity, pharmacokinetics, pharmacodynamics, progression-free survival, and overall survival will be evaluated.
- Conditions
- Recurrent Glioblastoma, Refractory Glioblastoma
- Being tested
- BP102 (B7-H3 CAR-T)
- Keywords
- Chimeric Antigen Receptor (CAR)-T, Glioblastoma
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BP102 (B7-H3 CAR-T)Drug
BP102 is an autologous B7-H3 CAR-T cell product manufactured from the participant's peripheral blood mononuclear cells. It will be administered into the tumor cavity or cerebral ventricle through an implanted Ommaya reservoir.
| Study group | Role | What they receive |
|---|---|---|
| BP102 (B7-H3 CAR-T) | Experimental | Participants will receive three planned BP102 treatment cycles at approximately 1- to 2-week intervals. Dose escalation will follow the protocol-defined intra-participant and inter-participant 3+3 rules. Additional cycles may be administered to participants who respond to treatment based on the investigator's risk-benefit assessment. Receives: Drug: BP102 (B7-H3 CAR-T) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and type of adverse events
Number of Participants With Treatment-Related Adverse Events and Types of adverse events as Assessed by CTCAE v5.0
Measured: 12 weeks
Maximum tolerated dose (MTD)
The highest dose of B7-H3 CAR-T that does not cause targeted dose limiting toxicity
Measured: 12 weeks
Overall survival (OS)
Kaplan Meier methods will be used to estimate median OS
Measured: 2 years, up to 15 years if necessary
Progression-free survival (PFS)
Kaplan Meier methods will be used to estimate median PFS. Progression is defined by Response Assessment in Neuro-Oncology (RANO) criteria
Measured: 2 years, up to 15 years if necessary
Secondary outcomes (3)
The pharmacokinetics (PK) of B7-H3 CAR-T
Peak Concentration (Cmax) of B7-H3 CAR-T in peripheral blood (PB) and cerebral spinal fluid (CSF)
Measured: 12 weeks
The pharmacokinetics (PK) of B7-H3 CAR-T
Area under the concentration versus time curve (AUC) of B7-H3 CAR-T in peripheral blood (PB) and cerebral spinal fluid (CSF)
Measured: 12 weeks
Disease response (ORR, CR, PR, DOR)
Objective Response Rate (ORR) will be assessed by comparison with baseline magnetic resonance imaging by RANO. Complete Response (CR) is disappearance of all measurable and non-measurable disease for at least 4 weeks. Partial Response (PR) is >/= 50% decrease in lesions for at least 4 weeks. Duration of Response (DOR) is the time between the initial response to the treatment and subsequent disease progression.
Measured: 2 years, up to 15 years if necessary
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2020
- Study start1 Dec 2022
- Primary completion1 Sep 2026
- Study completion1 Sep 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- BoYuan RunSheng Pharma (Hangzhou) Co., Ltd.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04385173
- Sponsor's protocol ID
- SAHZJU-BP102
- Status last verified
- Sep 2026
- First submitted
- 4 Feb 2020
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided