Neoplasms

All Conditions

Rare Diseases

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

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

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.

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.

GPC2 CAR T cells

Melissa Varghese

Yael Mosse, MD

Lisa Wray, MD

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

Despite the use of intensive multimodal chemoradiotherapy, surgery, autologous stem cell transplant and disialoganglioside antigen (GD2)-targeted immunotherapy for the treatment of patients with high-risk neuroblastoma, approximately 60% of children still die from this disease and survivors suffer lifelong treatment related comorbidities. For patients who suffer a relapse after receiving therapy with standard of care multimodality treatment, there are no known curative options. Glypican 2 (GPC2) is highly expressed on the plasma membrane of most high-risk neuroblastomas, is further enriched in the tumor stem cell compartment, but is not expressed at significant levels on normal tissues, making it an ideal target for immune directed therapies. To therapeutically leverage GPC2's differential expression, a GPC2-directed CAR T cell therapy that potently inhibits the growth of neuroblastoma patient-derived xenografts has been developed. This investigation will be a single institution, open-label first in human, dose escalation and expansion study designed to assess the safety, tolerability, and manufacturing feasibility of GPC2 CAR T cells.

GPC2 CAR T Cells for Relapsed or Refractory Neuroblastoma

Phase 1 Trial of GPC2-Directed Chimeric Antigen Receptor Autologous T Cells (GPC2 CAR T) for Relapsed or Refractory Neuroblastoma

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.

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

Manufacturing Feasibility will be evaluated as the Percentage of patients with GPC2 CAR T cell products that meet release criteria

Persistence of GPC2 CAR T cells will be measured by Polymerase Chain Reaction (or flow cytometry) analysis of whole blood to detect and quantify survival of GPC2 CAR T cells over time.

Overall Response Rate will be determined based on international Neuroblastoma Response Criteria

The safety of GPC2 CAR T cell therapy reinfusions will be measured by the monitoring the frequency and severity of adverse events after multipleGPC2 CAR T cells infusions.

Children's Hospital of Philadelphia

Gilead Sciences

University of Pennsylvania

Stephan Grupp MD PhD

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 title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
GPC2 CAR T Cells for Relapsed or Refractory Neuroblastoma	NCT05650749	Refractory Neur... Relapsed Neurob... High-risk Neuro...	GPC2 CAR T cell...	1 Year -	Children's Hospital of Philadelphia
GPC2 CAR T Cells for Relapsed or Refractory Neuroblastoma	NCT05650749	Refractory Neur... Relapsed Neurob... High-risk Neuro...	GPC2 CAR T cell...	1 Year -	Children's Hospital of Philadelphia

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