NCT07513194

GPC3 CAR T Cells With IL-15 and IL-21 for Recurrent ATRT and CNS Rhabdoid Tumors (RADIANT)

Robust Armored Dual-Cytokine (IL-15/IL-21) GPC3-CAR T Cells for Atypical Teratoid Rhabdoid Tumors and Central Nervous System Rhabdoid Tumors (RADIANT)

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 21 (estimated)
• Sponsor: Baylor College of Medicine · Academic / Other
• Sex: All
• Age: 1 Year – 21 Years
• Healthy volunteers: Not accepted

Summary

This study is being conducted in patients with GPC3-positive brain tumors that have recurred or have not responded to standard therapy. Atypical teratoid rhabdoid tumors (ATRT) are aggressive tumors with poor outcomes and limited treatment options, particularly in young children. There is a need for new therapies that can improve outcomes while minimizing toxicity. This study evaluates a new experimental treatment using genetically engineered T cells (RADIANT-T cells) that target glypican-3 (GPC3), a protein expressed on tumor cells. These T cells are modified to express a chimeric antigen receptor (CAR) targeting GPC3, along with IL-15 and IL-21 to enhance their persistence and activity. The cells also include an inducible safety mechanism (iCasp9) that allows them to be eliminated if necessary. The purpose of this study is to determine the highest safe dose of RADIANT-T cells, evaluate their safety and side effects, assess how long they persist in the body, and determine whether they show anti-tumor activity in patients with GPC3-positive brain tumors.

Detailed description

This is a Phase 1 dose-escalation study conducted at Texas Children's Hospital to evaluate RADIANT-T cells in patients with GPC3-positive brain tumors. Approximately 15-24 subjects will participate in the treatment portion of the study. Autologous T cells are collected from the patient and genetically engineered using a retroviral vector to express a GPC3-specific chimeric antigen receptor along with IL-15 and IL-21. The modified T cells are expanded and tested for activity against GPC3-positive tumor cells prior to administration. Patients receive a single dose of RADIANT-T cells administered intracavitarily during a planned surgical resection. Prior to administration, patients may receive premedication to reduce the risk of infusion reactions. During surgery, an Ommaya reservoir is placed to allow monitoring and management of potential treatment-related effects. This is a dose-escalation study in which groups of patients receive increasing dose levels of RADIANT-T cells to determine the maximum tolerated dose. The dose administered to each patient depends on prior patient outcomes at lower dose levels. Patients undergo clinical evaluations before treatment, including physical examination, laboratory testing, and imaging studies. After treatment, patients are monitored with physical exams, laboratory tests, cerebrospinal fluid assessments, and imaging to evaluate safety and tumor response. Tumor assessments are performed by MRI at approximately 1 week and 4-6 weeks after treatment. Patients are followed longitudinally to assess safety, persistence of the modified T cells, and clinical outcomes. Long-term follow-up continues for up to 15 years after infusion, with more frequent visits early after treatment and less frequent visits over time.

Conditions

• Atypical Teratoid Rhabdoid Tumor
• Central Nervous System Rhabdoid Tumor

Interventions

Type	Name	Description
BIOLOGICAL	21.15.GPC3-CAR T Cells	Autologous T cells genetically engineered using retroviral vectors encoding a GPC3-specific CAR and IL-15 and IL-21 cytokines. The product also includes an inducible caspase-9 safety switch allowing pharmacologic elimination of the CAR T cells in the event of severe toxicity.

Timeline

• Start date: 2026-09-01
• Primary completion: 2029-10-31
• Completion: 2044-10-31
• First posted: 2026-04-07
• Last updated: 2026-04-07

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study