GPC2 CAR T Cells for Relapsed or Refractory Neuroblastoma and Metastatic Retinoblastoma

NCT05650749 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 22-0196591R37CA282041-01A122CT012
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This is a first in human dose escalation trial to determine the safety of administering GPC2 CAR T cells in patients with advanced neuroblastoma or retinoblastoma.

Conditions

Refractory Neuroblastoma; Relapsed Neuroblastoma; High-risk Neuroblastoma; Retinoblastoma; Metastatic Retinoblastoma

Outcome Measures

Primary Outcomes (2)

• Determine the Maximum Tolerated Dose of GPC2 CAR T cells

  The Maximum Tolerated Dose of GPC2 CAR T cells will be determined by measuring the incidence of dose limiting toxicities following administration of the product.

  5 years

• Frequency of Adverse Events Following GPC2 CAR T cell administration

  Assess the frequency and severity of treatment related adverse events following administration of GPC2 CAR T cells.

  5 years

Secondary Outcomes (4)

• Manufacturing Feasibility of GPC2 CAR T cells

  5 years

• Persistence of GPC2 CAR T cells

  5 years

• Preliminarily define the clinical activity of GPC2 CAR T in patients with relapsed or refractory neuroblastoma or metastatic retinoblastoma

  5 years

• Severity of Adverse Events Following GPC2 CAR T cell administration.

  5 years

Study Arms (2)

Dose Escalation Arm

EXPERIMENTAL

The dose escalation arm will determine the maximum tolerated dose of GPC2 CAR T cells using a standard 3+3 trial design.

Biological: GPC2 CAR T cells

Dose Expansion Arm

EXPERIMENTAL

If at least one dose from the dose expansion arm is determined to be safe, additional patients will be enrolled to the dose expansion arm to preliminarily evaluate the rate of response to GPC2 CAR T cells and further characterize the safety profile of GPC2 CAR T cells.

Biological: GPC2 CAR T cells

Interventions

GPC2 CAR T cells BIOLOGICAL

The GPC2 CAR T investigational product is comprised of autologous human T cells that have been genetically modified to express a GPC2-targeting chimeric antigen receptor (CAR) transgene.

Dose Escalation Arm; Dose Expansion Arm

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be ≥ 1 year of age
• Patients must have high-risk neuroblastoma according to COG risk classification at the time of study enrollment. Patients who were initially considered low- or intermediate-risk, but then reclassified as high-risk are also eligible.
• Patients must have a previously histologically confirmed diagnosis of neuroblastoma:
• That is recurrent/relapsed or refractory/persistent according to INRC AND
• For which standard curative measures do not exist or are no longer effective.
• patients at first relapse are eligible as no known curative therapies exist for relapsed high-risk neuroblastoma.
• Patients must have evaluable or measurable disease at enrollment.
• In addition, patient must have experienced at least one of the following:
• a. New disease site documented on at least one of the following: i. 123I-meta-iodobenzylguanidine (MIBG) or 18F-mFBG (meta-fluorobenzylguanidine) scan; OR ii. CT/MRI; OR iii. FDG or Ga-68 Dotatate PET (in patients known to have MIBG non-avid tumor) and MRI findings consistent with tumor (i.e., bone lesions), OR iv. Biopsy confirmed neuroblastoma for any new or progressing lesion. b. Greater than 20% increase in a least one dimension of soft tissue mass documented by CT/MRI and a minimum absolute increase of 5 mm in longest dimension in existing lesion(s). Previously irradiated lesions may be included.
• c. Bone marrow biopsy shows progressive disease according to the revised INRC d. Stable persistent disease, such that response at the completion of upfront therapy or salvage therapy is less than partial response AND has a biopsy of at least one site showing viable neuroblastoma.
• e. Responding persistent disease, defined as at least a partial response to frontline therapy (i.e., at least a partial response to frontline therapy but still has residual disease by MIBG scan, CT/MRI, or bone marrow aspirations/biopsies). Patients in this category are required to have histologic confirmation of viable neuroblastoma from at least one residual site (tumor seen on routine bone marrow morphology is sufficient).
• Patients must have a Lansky (≤ 16 years) or Karnofsky (\> 16 years) score of ≥ 60
• Patients must have adequate renal function defined as age-adjusted serum creatinine ≤1.5 ULN for age.
• Total bilirubin ≤ 1.5 x ULN (exception: total bilirubin ≤ 3 ULN for patients with Gilbert's Disease)
• Aspartate aminotransferase (AST) ≤ 2.5 ULN (exception: AST ≤ 5 x ULN for patients with liver metastases).

You may not qualify if:

• Patients with active hepatitis B or active hepatitis C.
• Patients with HIV infection.
• Patients with uncontrolled active infection.
• Patients with primary or acquired immunodeficiency disorder.
• Patients with a known hypersensitivity to DMSO.
• Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
• Patients with actively progressing CNS metastases, including parenchymal or leptomeningeal involvement. (Note: CNS imaging at screening is only required if the there is a clinical indication of suspected CNS metastasis)
• Active medical disorder that, in the opinion of the investigator, would substantially increase the risk of uncontrollable CRS and/or neurotoxicity.
• Patients with congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry or a history of myocarditis.
• Patients who have received any live vaccines within 30 days prior to enrollment.
• Patients who are pregnant or nursing (lactating).
• Patients who have a life expectancy \< 6 months at time of consent.
• Patient age ≥ 6 months.
• Patients must have metastatic retinoblastoma according to International
• Retinoblastoma Staging System (IRSS) risk classification (4) at the time of study enrollment:

Sponsors & Collaborators

• Stephan Grupp MD PhD: lead
• Children's Hospital of Philadelphia: collaborator
• Gilead Sciences: collaborator
• University of Pennsylvania: collaborator
• National Cancer Institute (NCI): collaborator
• Kite, A Gilead Company: collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Related Publications (1)

• Giudice AM, Matlaga S, Roth SL, Gladney W, Groff D, Hofmann TJ, McDaid KS, Pascual-Pasto G, McIntyre B, Zecchino V, Martinez D, Spear TT, Wolpaw AJ, Assenmacher CA, Radaelli E, Pogoriler J, Pawel B, Barrett D, Grupp SA, Maris JM, Bosse KR. D3-GPC2-Directed CAR T Cells Are Safe and Efficacious in Preclinical Models of Neuroblastoma and Small Cell Lung Cancer. Clin Cancer Res. 2025 Dec 15;31(24):5276-5293. doi: 10.1158/1078-0432.CCR-25-0089.

  PMID: 41026583 DERIVED

MeSH Terms

Conditions

Neuroblastoma; Retinoblastoma

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Retinal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases

Study Officials

• Lisa Wray, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

CART Nurse Navigator

CONTACT

445-942-5891; CARTNurseNavigator@chop.edu

Melissa Varghese, M.S.

CONTACT

8455535358; varghesem@chop.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Cell Therapy and Transplant Section Director, Susan S. and Stephen P. Kelly Center for Cancer Immunotherapy Medical Director, Cell and Gene Therapy Lab

Study Record Dates

• First Submitted: December 6, 2022
• First Posted: December 14, 2022
• Study Start: May 23, 2023
• Primary Completion (Estimated): January 30, 2028
• Study Completion (Estimated): January 30, 2030
• Last Updated: December 29, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)