NCT05650749

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

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 45 (estimated)
• Sponsor: Stephan Grupp MD PhD · Academic / Other
• Sex: All
• Age: 1 Year
• Healthy volunteers: Not accepted

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.

Detailed description

Despite the use of intensive multimodal chemoradiotherapy, surgery, autologous stem cell transplant and 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. Similarly, children with retinoblastoma with extra-ocular metastasis experience a poor prognosis despite the availability of intensive systemic chemotherapy or external beam radiation therapy. Among children with metastatic retinoblastoma treated with intensive multimodality treatment, 3-year Event Free Survival ranges from 14 to 77% depending on central nervous system (CNS) involvement. For neuroblastoma and retinoblastoma 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 and retinoblastomas, 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, we have developed a GPC2-directed CAR T cell therapy that potently inhibits the growth of neuroblastoma and retinoblastoma patient-derived xenografts. 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.

Conditions

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

Interventions

Type	Name	Description
BIOLOGICAL	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.

Timeline

• Start date: 2023-05-23
• Primary completion: 2028-01-30
• Completion: 2030-01-30
• First posted: 2022-12-14
• Last updated: 2025-12-29

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study