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

NCT06198296 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: H-54859 CO-EXIST
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

GPC3-positive tumors; GPC3-CAR T cells

Outcome Measures

Primary Outcomes (1)

• Number of Patients with Dose Limiting Toxicity

  A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the GPC3-CAR T cells. Specifically those which are Grade 5; non-hematologic Grade 3-4 not returning to Grade 2 within 72 hours; Grade 2-4 allergic reaction; Hematologic Grade 4 that fails to return to Grade 2 or baseline (whichever is more severe) within 14 days; all grade 4 CRS and neurologic toxicities and grade 3 CRS and neurologic toxicities that fail to return to Grade 1 within 7 days

  4 weeks

Secondary Outcomes (2)

• Percent of Patients with best response as either complete remission or partial remission

  4 weeks

• Median T cell persistence

  15 years

Study Arms (1)

21.15.GPC3-CAR T cells

EXPERIMENTAL

GPC3-CAR and the IL15 plus IL21 will be administered to patients with GPC3-positive solid tumors.

Genetic: 21.15.GPC3-CAR T cells

Interventions

21.15.GPC3-CAR T cells GENETIC

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

21.15.GPC3-CAR T cells

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of GPC3-positive\* solid tumors (as determined by immunohistochemistry with an extent score of \>=Grade 2 \[\>25% positive tumor cells\] and an intensity score of \>= 2 \[scale 0-4\]).
• Age ≥21 years
• Lansky or Karnofsky score ≥60%
• Life expectancy ≥16 weeks
• Barcelona Clinic Liver Cancer Stage A, B or C (- Child-Pugh-Turcotte score \<7 (for patients with hepatocellular carcinoma only)
• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent \* GPC3 expression will be evaluated by standard immunohistochemistry (IHC) at Texas Patients's Hospital/Baylor College of Medicine, Department of Pathology for all patients to meet procurement eligibility. All patients will send at least 5 unstained slides.

You may not qualify if:

• History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies).
• History of organ transplantation
• Known HIV positivity
• Active bacterial, fungal or viral infection (except Hepatitis B or Hepatitis C virus infections)
• Diagnosis of GPC3-positive solid tumor
• Age ≥ 21 years
• Barcelona Clinic Liver Cancer Stage A, B or C
• Life expectancy of ≥ 12 weeks
• Lansky or Karnofsky score ≥ 60%
• Child-Pugh-Turcotte score \< 7
• Adequate organ function:
• Creatinine clearance as estimated by Cockcroft Gault or Schwartz ≥ 60 ml/min
• total bilirubin \< 3 times ULN for age
• INR ≤1.7 (for patients with hepatocellular carcinoma only)
• absolute neutrophil count \> 500/µl

Sponsors & Collaborators

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

Study Sites (1)

Houston Methodist Hospital

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Hepatoblastoma; Carcinoma, Hepatocellular; Wilms Tumor; Rhabdoid Tumor; Endodermal Sinus Tumor; Rhabdomyosarcoma; Liposarcoma

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mesonephroma; Neoplasms, Germ Cell and Embryonal; Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Neoplasms, Adipose Tissue

Study Officials

• Premal Lulla, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• David Steffin, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Premal Lulla, MD

CONTACT

(713) 441-1450; lulla@bcm.edu

David Steffin, MD

CONTACT

(832) 824-4233; dhsteffi@texaschildrens.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 27, 2023
• First Posted: January 10, 2024
• Study Start: June 10, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2043
• Last Updated: November 3, 2025

Record last verified: 2025-10

Locations

US (1)