Autologous CAR-T Cells Targeting B7-H3 in Recurrent or Refractory GBM CAR.B7-H3Tc

NCT05366179 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: LCCC2059-ATL
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the safety of using T lymphocyte chimeric antigen receptor cells against the B7-H3 antigen (CAR.B7-H3T cells) in patients with glioblastoma. CAR.B7-H3T cells treatment has not been tested in humans and is not an approved treatment by the Food and Drug Administration for glioblastoma.

Conditions

Glioblastoma Multiforme

Keywords

Brain Tumor; Glioblastoma Multiforme; Cell therapy; Relapse; Recurrent

Outcome Measures

Primary Outcomes (3)

• Number of participants with adverse event

  Number of participants with adverse event (AE)s as a measure of safety and tolerability of intraventricular administration CAR.B7-H3 T cells in subjects with progressive recurrent or refractory glioblastoma multiforme. AEs will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Dose Limiting Toxicities (DLTs) are defined as at least possibly related to CAR.B7-H3T cell product administration.

  Up to 10 weeks

• Cytokine Release Syndrome

  Cytokine Release Syndrome (CRS) will be graded according to American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading. Grade 1 - Mild (Symptomatic Management): Fever ≥38\^ o C, No hypotension, No hypoxia, Grade 2 - Moderate (Moderate Intervention): Fever ≥38\^ o C, Hypotension not requiring vasopressors, Hypoxia requiring low-flow nasal cannula (≤6 L/minute) or blow-by, Grade 3 - Severe (Aggressive Intervention): Fever ≥ 38\^ o C , Hypotension requiring a vasopressor with or without vasopressin, Hypoxia requiring high-flow nasal cannula (\>6 L/minute), facemask, nonrebreather mask, or Venturi mask, Grade 4 - Life-threatening (Life-sustaining intervention): Fever ≥38\^oC, Hypotension requiring multiple vasopressors (excluding vasopressin),Hypoxia requiring positive pressure (e.g. Continuous positive airway pressure, BiPAP, intubation, mechanical ventilation), Grade 5 - Death: Death.

  Up to 10 weeks

• Neurotoxicity

  Neurotoxicity will be graded according to the Central Nervous System (CNS) Toxicity criteria. Grade 0: Normal or no change from baseline exam at start of therapy, Grade 1: Mild lethargy and/or irritability or visual, motor, or sensory symptoms without change in neurological exam, Grade 2: Moderate lethargy, disorientation, or psychosis lasting \< 48 hours or mild increase in pre-existing neurological deficit, Grade 3: \>48hours of severe lethargy, but responsive to verbal stimuli or disorientation or psychosis lasting \>48 hours, Grade 4: Coma, unresponsive to verbal stimuli, increasing neurological deficit above grade 3, evidence of herniation, development of uncontrolled seizures, intracerebral hemorrhage.

  Up to 10 weeks

Secondary Outcomes (5)

• Identification of Recommended phase 2 dose (RP2D)

  Up to 4 weeks

• Objective Response Rate (ORR)

  Up to 4 weeks

• Progression Free Survival (PFS)

  Up to 12 months

• Overall Survival (OS)

  Up to 5 years

• Duration of Response (DOR)

  Up to 12 months

Study Arms (1)

Single Arm

EXPERIMENTAL

CAR.B7-H3 T cells: Subjects with refractory or recurrent glioblastoma multiforme, have cells collected following their initial surgical resection to manufacture CAR.B7-H3 T cells, preferably before initiation of adjuvant chemoradiation.

Drug: CAR.B7-H3T cells infusion

Interventions

CAR.B7-H3T cells infusion DRUG

The Chimeric Antigen Receptors (CAR).B7-H3T cells will be administered via intraventricular infusion up to 3 weekly infusions. A suspension of T cells infusion is given, over 5-10 minutes, via a Rickham catheter and will be followed by a normal-saline flush. Dose escalation will be performed considering the dose limiting toxicities (DLTs) listed in the protocol. Six doses will be explored. The starting dose will be 2 × 10\^6 transduced cells/infusion (Dose Level (DL) 1) and will enroll at least 3 subjects. If there are no dose DLTs within 4 weeks of the third cellular product administration in the first 3 subjects, then the next cohort will evaluate 5 × 10\^6 transduced cells/infusion (DL2).

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Karnofsky score of \> 60%
• Diagnosis or recurrent supratentorial- or infra-tentorial glioblastoma multiforme (GBM) (World Health Organization 2016 or 2021) based on Response assessment in neuro-oncology criteria (RANO) magnetic resonance imaging (MRI) criteria. Disseminated GBM down the spinal cord is not allowed. Must have previously undergone resection or biopsy at initial diagnosis.
• Must have undergone at least 4005 cGy of radiation with concurrent temozolomide.
• No current or previous exposure to antiangiogenic agents, such as bevacizumab.
• Female subjects of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 6 months after study treatment discontinuation.
• Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception starting with the first dose of study therapy through 3 months after the cell infusion therapy. If a male subject receives multiple infusions, they must remain on contraception throughout the duration and 3 months after the last cell infusion therapy.
• The subject is willing and able to comply with study procedures based on the judgment of the investigator.

You may not qualify if:

• Subject is pregnant or lactating (Note: Breast milk cannot be stored for future use while the mother is being treated on study).
• Subjects with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
• Active infection with HIV, hepatitis B virus, hepatitis C virus (HCV). Note: To meet eligibility subjects are required to be negative for HIV antibody, negative for HTLV1 and 2 antibodies, negative for Hepatitis B surface antigen, and negative for HCV antibody and viral load.
• Contraindication to MRI contrast agents or an inability to undergo MRI scans due to MRI non-compatible implanted materials.
• Prior exposure to chimeric antigen receptor T cell therapy for treatment of glioblastoma.
• Evidence of disseminated disease involving the brainstem, cerebellum or spinal cord.
• Previously implanted carmustine wafers or brachytherapy for the treatment of glioma.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead

Study Sites (1)

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Related Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms; Recurrence

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Felicia Cao, MD, PhD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Catherine Cheng

CONTACT

919-445-4208; UNCImmunotherapy@med.unc.edu

Caroline Babinec

CONTACT

919-962-7426; UNCImmunotherapy@med.unc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2022
• First Posted: May 9, 2022
• Study Start: September 2, 2022
• Primary Completion (Estimated): May 30, 2030
• Study Completion (Estimated): May 30, 2030
• Last Updated: April 22, 2026

Record last verified: 2026-04

Locations

US (1)