GPC3 CAR T Cells for Brain Tumors

Overseen By Ramy Sweiden

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Anti-cancer therapy

Disqualifiers: Pregnancy, HIV, Organ transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Who Is on the Research Team?

David Steffin, MD

Principal Investigator

Baylor College of Medicine

Jasia Mahdi, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

Inclusion Criteria

I have recurrent ATRT that tests positive for GPC3.

I am at least 6 months old.

I am able to care for myself and do most daily activities.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive a single dose of RADIANT-T cells administered intracavitarily during a planned surgical resection

1 day

1 visit (in-person)

Initial Follow-up

Patients are monitored with physical exams, laboratory tests, cerebrospinal fluid assessments, and imaging to evaluate safety and tumor response

4-6 weeks

Multiple visits (in-person)

Long-term Follow-up

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

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• 21.15.GPC3-CAR T Cells

How Is the Trial Designed?

Group I: Treatment with 21.15.GPC3-CAR T Cell Therapy (RADIANT CAR T Cells) Experimental Treatment 1 Intervention

Participants will receive autologous 21.15.GPC3-CAR T cells administered intratumorally into the tumor resection cavity and/or intracerebroventricularly via an Ommaya reservoir. CAR T cells are genetically engineered using retroviral vectors encoding a GPC3-specific chimeric antigen receptor and cytokines IL-15 and IL-21. The following dose levels of CAR T cells will be evaluated: * DL0: 1 × 10⁷ CAR T cells * DL1: 3 × 10⁷ CAR T cells * DL2: 5 × 10⁷ CAR T cells * DL3: 1 × 10⁸ CAR T cells If dose de-escalation from DL1 is required, patients will be treated at DL0. Further de-escalation may use half-log reductions if needed. Dose escalation will occur only after safety evaluation of prior cohorts.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+