Immunotherapy For Adults With GPC3-Positive Solid Tumors Using IL-15 and IL-21 Armored GPC3-CAR T Cells

Summary

The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells.

Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise but have not been strong enough to cure most patients.

In order to get them to kill cancers more effectively, in the laboratory, the study team inserted a new gene called a chimeric antigen receptor (CAR) into T cells that makes them recognize cancer cells and kill them. When inserted, this new CAR T cell can specifically recognize a protein found on solid tumors, called glypican-3 (GPC3). To make this GPC3-CAR more effective, the study team also added two genes called IL15 and IL21 that help CAR T cells grow better and stay in the blood longer so that they may kill tumors better. When the study team did this in the laboratory, they found that this mixture of GPC3-CAR,IL15 and IL21 killed tumor cells better when compared with CAR T cells that did not have IL15 plus IL21 in the laboratory. This study will use those cells, which are called 21.15.GPC3-CAR T cells, to treat patients with solid tumors that have GPC3 on their surface.

The study team also wanted to make sure that they could stop the 21.15.GPC3-CAR T cells from growing in the blood should there be any bad side effects. In order to do so, they inserted a gene called iCasp9 into the CO-EXIST T cells. This allows us the elimination of 21.15.GPC3-CAR T cells in the blood when the gene comes into contact with a medication called AP1903. The drug (AP1903) is an experimental drug that has been tested in humans with no bad side-effects. This drug will only be used to kill the T cells if necessary due to side effects .

The study team has treated patients with T cells that include GPC3. Patients have also been treated with IL-21 and with IL-15. Patients have not been treated with a combination of T cells that contain GPC3, IL-21 and IL-15. To summarize, this study will test the effect of 21.15.GPC3-CAR T cells in patients with solid tumors that express GPC3 on their surface.

The 21.15.GPC3-CAR T cells are an investigational product not yet approved by the Food and Drug Administration.

Conditions

• Hepatoblastoma
• Hepatocellular Carcinoma
• Wilms Tumor
• Malignant Rhabdoid Tumor
• Yolk Sac Tumor
• Rhabdomyosarcoma
• Liposarcoma
• Embryonal Sarcoma of Liver

Interventions

GENETIC

21.15.GPC3-CAR T cells

Three different dosing schedules will be evaluated. The following dose levels will be evaluated: The following dose levels will be evaluated: DL0: 3x10\^7/m2 DL1: 1x10\^8/m2 DL2: 3x10\^8/m2 DL3: 1x10\^9/m2

Sponsors & Collaborators

• Center for Cell and Gene Therapy, Baylor College of Medicine

  collaborator OTHER

• Baylor College of Medicine

  lead OTHER

Principal Investigators

• Premal Lulla, MD · Baylor College of Medicine

• David Steffin, MD · Baylor College of Medicine

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-06-10

Primary Completion

2028-02-01

Completion

2043-02-01

FDA Drug

Yes

Countries

• United States

Study Locations