NCT07551336

Brief Summary

This is a draft, ClinicalTrials.gov-style example record for a first-in-human Phase 1 study evaluating locoregional administration of dual-targeting chimeric antigen receptor natural killer (CAR-NK) cells in adults with recurrent or progressive glioblastoma (GBM) or other high-grade glioma (HGG). Participants will undergo tumor antigen profiling for IL13Rα2, EGFR/EGFRvIII, and B7-H3 (CD276). Based on this assessment, each participant will receive the most suitable dual-target CAR construct to reduce antigen-escape risk.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
36

participants targeted

Target at P50-P75 for phase_1

Timeline
24mo left

Started Mar 2026

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress9%
Mar 2026Apr 2028

Study Start

First participant enrolled

March 2, 2026

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

April 18, 2026

Completed
6 days until next milestone

First Posted

Study publicly available on registry

April 24, 2026

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 14, 2027

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

April 17, 2028

Last Updated

April 24, 2026

Status Verified

April 1, 2026

Enrollment Period

1.1 years

First QC Date

April 18, 2026

Last Update Submit

April 18, 2026

Conditions

Malignant GliomaRecurrent GlioblastomaHigh-Grade GliomasGlioblastomaRecurrent High-Grade Gliomas

Keywords

CAR-NKDual targetingBiomarker-guidedIL13Rα2EGFREGFRvIIIB7-H3 (CD276)LocoregionalIntracavitaryOmmaya reservoir

Outcome Measures

Primary Outcomes (2)

  • Incidence of dose-limiting toxicities (DLTs) after CAR-NK infusion (CTCAE v5.0; CRS and ICANS grading).

    28 Days

  • Determination of recommended phase 2 dose (RP2D)

    Determination of recommended phase 2 dose (RP2D) if the maximum tolerated dose (MTD) for each biomarker-defined cohort has been established

    12 months

Secondary Outcomes (2)

  • Objective response rate (ORR) by RANO criteria (CR+PR)

    12 months

  • Disease control rate (DCR) by RANO criteria

    6 months

Study Arms (3)

IL13Rα2 + EGFR/EGFRvIII Dual-Target CAR-NK

EXPERIMENTAL

Participants whose tumors meet eligibility thresholds for IL13Rα2 and EGFR will receive a dual-target (tandem) CAR-NK product recognizing IL13Rα2 and EGFR/EGFRvIII

Biological: Dual-target CAR-NK cellsDrug: CyclophosphamideDevice: Intracranial catheter/reservoir for locoregional deliveryDrug: Fludarabine

IL13Rα2 + B7-H3 (CD276) Dual-Target CAR-NK

EXPERIMENTAL

Participants whose tumors meet eligibility thresholds for IL13Rα2 and B7-H3 (CD276) will receive a dual-target (tandem) CAR-NK product recognizing IL13Rα2 and B7-H3.

Biological: Dual-target CAR-NK cellsDrug: CyclophosphamideDevice: Intracranial catheter/reservoir for locoregional deliveryDrug: Fludarabine

EGFR/EGFRvIII + B7-H3 (CD276) Dual-Target CAR-NK

EXPERIMENTAL

Participants whose tumors meet eligibility thresholds for EGFR (and/or EGFRvIII) and B7-H3 (CD276) will receive a dual-target (tandem) CAR-NK product recognizing EGFR/EGFRvIII and B7-H3.

Biological: Dual-target CAR-NK cellsDrug: CyclophosphamideDevice: Intracranial catheter/reservoir for locoregional deliveryDrug: Fludarabine

Interventions

Intracranial catheter/reservoir for locoregional deliveryDEVICE

A device (e.g., Ommaya reservoir) implanted in the brain to enable direct, repeated administration of CAR-NK cells or other therapies into the tumor site or cerebrospinal fluid, improving local drug delivery and reducing systemic exposure.

EGFR/EGFRvIII + B7-H3 (CD276) Dual-Target CAR-NKIL13Rα2 + B7-H3 (CD276) Dual-Target CAR-NKIL13Rα2 + EGFR/EGFRvIII Dual-Target CAR-NK
Dual-target CAR-NK cellsBIOLOGICAL

Dual-target CAR-NK cells (IL13Rα2/EGFR/EGFRvIII construct): Allogeneic natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) designed to recognize tumor-associated antigens including IL13Rα2, EGFR, and EGFRvIII. This multi-targeting strategy aims to enhance tumor recognition, reduce antigen escape, and improve cytotoxic activity against heterogeneous tumor cell populations. The engineered CAR-NK cells are administered via locoregional delivery (e.g., intracavitary or through an Ommaya reservoir) to achieve targeted anti-tumor effects while minimizing systemic toxicity.

EGFR/EGFRvIII + B7-H3 (CD276) Dual-Target CAR-NKIL13Rα2 + B7-H3 (CD276) Dual-Target CAR-NKIL13Rα2 + EGFR/EGFRvIII Dual-Target CAR-NK
CyclophosphamideDRUG

An alkylating chemotherapy agent used as part of lymphodepleting conditioning prior to CAR-NK cell infusion to enhance cell expansion, persistence, and anti-tumor activity.

EGFR/EGFRvIII + B7-H3 (CD276) Dual-Target CAR-NKIL13Rα2 + B7-H3 (CD276) Dual-Target CAR-NKIL13Rα2 + EGFR/EGFRvIII Dual-Target CAR-NK
FludarabineDRUG

A purine analog chemotherapy used in lymphodepletion prior to CAR-NK cell therapy to enhance the expansion, persistence, and anti-tumor activity of the infused cells.

EGFR/EGFRvIII + B7-H3 (CD276) Dual-Target CAR-NKIL13Rα2 + B7-H3 (CD276) Dual-Target CAR-NKIL13Rα2 + EGFR/EGFRvIII Dual-Target CAR-NK

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age 18 to 75 years at the time of consent.
  • Histologically confirmed glioblastoma (WHO grade 4) or diffuse high-grade glioma (WHO grade 3 or 4) that is recurrent or progressive after standard therapy.
  • Planned clinically indicated tumor resection or stereotactic biopsy (or availability of adequate archived tumor tissue) to support antigen testing and locoregional catheter placement.
  • Tumor demonstrates expression of at least two of the following antigens above protocol-defined thresholds: IL13Rα2, EGFR (wild-type) and/or EGFRvIII, B7-H3 (CD276).
  • Karnofsky Performance Status (KPS) ≥ 60.
  • Adequate organ function (hematologic, renal, hepatic) as defined by protocol laboratory criteria.
  • Ability to undergo brain MRI with contrast (unless contraindicated and alternative imaging is permitted).
  • Negative pregnancy test for women of childbearing potential; agreement to use effective contraception during study participation and for a protocol-defined period after infusion.
  • Ability to understand and willingness to sign informed consent.

You may not qualify if:

  • Active, uncontrolled infection (including uncontrolled bacterial, viral, or fungal infection).
  • Known HIV infection with uncontrolled viral load; active hepatitis B or hepatitis C with detectable viral load (unless permitted per protocol).
  • Clinically significant autoimmune disease requiring systemic immunosuppression within the past 6 months.
  • Requirement for high-dose systemic corticosteroids (e.g., \>4 mg/day dexamethasone equivalent) within 7 days prior to lymphodepletion/infusion (physiologic replacement permitted).
  • Prior gene-modified cellular therapy (e.g., prior CAR-T/CAR-NK) within 6 months, or prior therapy targeting IL13Rα2, EGFR/EGFRvIII, or B7-H3 where residual engineered cells could confound safety assessments.
  • Diffuse leptomeningeal disease as the only site of disease, or anatomy that precludes safe catheter placement (unless specifically allowed by protocol).
  • Uncontrolled seizures despite optimal medical therapy.
  • Clinically significant cardiovascular disease (e.g., recent myocardial infarction, uncontrolled arrhythmia) that would increase risk with lymphodepletion or infusion procedures.
  • Pregnant or breastfeeding.
  • Any condition that, in the investigator's judgment, would make the participant unsuitable for the study or could interfere with protocol adherence.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

GliomaGlioblastoma

Interventions

Cyclophosphamidefludarabine

Condition Hierarchy (Ancestors)

Neoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueAstrocytoma

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Central Study Contacts

shan S Lu, Phd

CONTACT

+86 13076790030Seni-Lu@beijing-biotech.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Masking Details
Open-label
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: Biomarker-guided, multi-cohort (umbrella) design. Participants are assigned to one of three cohorts based on tumor antigen expression, then treated in a cohort-specific modified 3+3 dose escalation followed by dose expansion at the recommended phase 2 dose (RP2D).
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 18, 2026

First Posted

April 24, 2026

Study Start

March 2, 2026

Primary Completion (Estimated)

April 14, 2027

Study Completion (Estimated)

April 17, 2028

Last Updated

April 24, 2026

Record last verified: 2026-04

Locations

CN(1)