GPC2-CAR T Cell Therapy for Relapsed or Refractory Medulloblastoma in Children and Young Adults

NCT07087002 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: IRB-79066NCI-2025-06836
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-site, open-label Phase 1 clinical trial evaluating the feasibility, safety, and preliminary activity of autologous GPC2-targeted chimeric antigen receptor (CAR) T cells administered via intracerebroventricular (ICV) infusion in children and young adults with relapsed or refractory medulloblastoma or other eligible Central Nervous System (CNS) embryonal tumors.

Conditions

Medulloblastoma; Central Nervous System Embryonal Tumor; Refractory Medulloblastoma; Recurrent Medulloblastoma; Pediatric Brain Tumor; Embryonal Tumor With Multilayered Rosettes (ETMR); Pineoblastoma; Atypical Teratoid/Rhabdoid Tumor (ATRT) of the CNS; CNS Neuroblastoma; FOXR2-activated

Keywords

GPC2-CAR T cells; Chimeric Antigen Receptor T cells; Intracerebroventricular CAR T; Pediatric CNS tumors; Immunotherapy; Medulloblastoma; Refractory brain tumors; T cell therapy; Embryonal Tumor with Multilayered Rosettes (ETMR); Pineoblastoma; Atypical Teratoid/Rhabdoid Tumor (ATRT) of the CNS; CNS neuroblastoma; FOXR2-activated

Outcome Measures

Primary Outcomes (2)

• Manufacturing Feasibility

  Proportion of manufacturing attempts that result in at least one dose of GPC2-CAR T cells that meet the IND release criteria and protocol-specified dose.

  Up to 6 months post-leukapheresis

• Incidence of Dose Limiting Toxicities (DLTs)

  Number and severity of DLTs following GPC2-CAR T cell administration at each dose level using protocol-defined criteria.

  Within first 28-day treatment cycle per dose level

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  Up to 2 years post-infusion

• Progression-Free Survival (PFS)

  Up to 2 years

• Overall Survival (OS)

  Up to 2 years

Study Arms (1)

GPC2-CAR T Cell Therapy

EXPERIMENTAL

Participants will undergo leukapheresis for collection of peripheral blood mononuclear cells, which will be used to manufacture autologous T cells transduced with a retroviral vector encoding a GPC2-targeted chimeric antigen receptor (GPC2-CAR T cells). After lymphodepleting chemotherapy with fludarabine and cyclophosphamide, participants will receive up to 8 cycles of intracerebroventricular (ICV) GPC2-CAR T cell infusions using an intrapatient dose escalation strategy.

Biological: GPC2-CAR T cells; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

GPC2-CAR T cells BIOLOGICAL

Autologous T cells transduced with retroviral vector encoding a second-generation GPC2-targeted chimeric antigen receptor (GPC2-CAR), administered intracerebroventricularly. Up to 8 doses are given every 28 days, following an intrapatient dose escalation schema.

Also known as: GPC2-directed CAR T cells

GPC2-CAR T Cell Therapy

Fludarabine DRUG

Administered as part of a lymphodepleting chemotherapy regimen prior to GPC2-CAR T cell infusion. Dose: 30 mg/m²/day for 3 days.

GPC2-CAR T Cell Therapy

Cyclophosphamide DRUG

Administered with fludarabine for lymphodepletion. Dose: 500 mg/m²/day for 3 days.

GPC2-CAR T Cell Therapy

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis: Histologically confirmed diagnosis of medulloblastoma or other primary CNS embryonal tumor according to 2021 CNS WHO Classification (5th edition)
• Other acceptable CNS embryonal tumors include:
• Embryonal Tumor with Multilayered Rosettes (ETMR)
• Pineoblastoma
• Atypical Teratoid/Rhabdoid Tumor (ATRT) of the CNS
• CNS neuroblastoma, FOXR2-activated
• CNS Embryonal Tumor NOS
• Recurrent/Refractory Disease: History of relapsed and/or recurrent disease defined as tumor progression or recurrence following initial diagnosis and upfront treatment with curative intent, or failure to achieve disease control with standard curative-intent therapy.
• GPC2 Positive: H-score ≥ 100 by IHC staining performed on the (Prescreening Protocol IRB-78780, PI: Katherine Ryan, DO) at Stanford Clinical Anatomic Pathology Lab for GPC2 from a tumor sample any time since initial diagnosis.
• Evaluable Disease: Evaluable disease as per radiographic findings and/or positive cerebrospinal fluid cytology within 28 days of enrollment.
• Patients with VP shunts: Patients with pre-existing ventriculo-peritoneal (VP) shunt devices must have a programmable shunt device to enroll on this study. A VP shunt is not a requirement for this study.
• Prior therapy: No limit to the number of prior treatment regimens. Toxicities due to prior therapy must be stable or recovered to ≤ Grade 1 (except for clinically non-significant toxicities such as alopecia, nutritional support measures, electrolyte abnormalities, or those not impacting the investigator's ability to assess treatment emergent toxicities).
• At time of enrollment, subjects are on track to meet the required therapy wash out period(s) prior to apheresis.
• a. At least 6 weeks following craniospinal radiation therapy. i. At least 14 days wash-out needed following small volume radiotherapy (i.e., Stereotactic Radiosurgery (SRS)).
• b. At least 21 days or 5 half-lives (whichever is shorter) must have elapsed since any prior systemic therapy, except for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5 half-lives.

You may not qualify if:

• Any patient with metastatic disease OUTSIDE the CNS.
• Unwilling or unable, in the investigator's judgement, to have a CSF reservoir (Ommaya or Rickham) placed. Does not apply to subjects who have a pre-existing device suitable for ICV delivery of CAR T cells and ICP monitoring.
• Clinical evidence of active/on-going significant increased intracranial pressure (i.e., impending herniation) or uncontrolled seizures.
• Prior receipt of a chimeric antigen receptor (CAR)-based therapy.
• Currently receiving anticoagulation therapy.
• Known history of infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive).
• EXCEPTION: A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing.
• Pregnancy or breastfeeding in a postpartum female.
• Known sensitivity or allergy to any agents/reagents used in this study.
• History of prior other malignancy. EXCEPTION: Previously diagnosed and definitively treated more than 5 years prior to enrollment or whose prognosis is deemed good enough to not warrant surveillance.
• Primary immunodeficiency or history of autoimmune disease (e.g., Crohn's, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment.
• Significant medical diseases or poorly controlled conditions that, in the judgement of the investigator, put the subject at an unacceptable risk of complications, including but not limited to: uncontrolled diabetes mellitus, chronic obstructive pulmonary disease, pulmonary fibrosis, clinically significant inflammatory disorders, immunodeficiency (e.g., HIV infection), immunocompromised for reasons other than malignancy (e.g., chronic corticosteroid therapy or other immunosuppressive therapy), renal failure including patients requiring dialysis, or clinically significant liver dysfunction.
• In the Investigator's judgment, the subject or parents/caregivers (as required) will not be able to comply with the study procedures outlined in the study protocol including follow-up visits.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Lucile Packard Children's Hospital Stanford

Palo Alto, California, 94304, United States

RECRUITING

MeSH Terms

Conditions

Medulloblastoma; Neuroectodermal Tumors, Primitive; Pinealoma; Rhabdoid Tumor; Brain Neoplasms

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

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; Neoplasms, Complex and Mixed

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Katherine Ryan, DO

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mariah Duncan

CONTACT

(650) 497-8953; GPC2CART@stanfordchildrens.org

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: June 24, 2025
• First Posted: July 25, 2025
• Study Start: August 28, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: January 27, 2026

Record last verified: 2026-01

Locations

US (1)