Interleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in Autologous T Cells for Solid Tumors

NCT05103631 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: H-49796 CATCH
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Patients may be considered if the cancer has come back, has not gone away after standard treatment or the patient cannot receive standard treatment. This research study uses special immune system cells called CATCH T cells, a new experimental treatment. 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. Investigators have found from previous research that we can put a new gene (a tiny part of what makes-up DNA and carriesa person's traits) into T cells that will make them recognize cancer cells and kill them . In the lab, we made several genes called a chimeric antigen receptor (CAR), from an antibody called GC33. The antibody GC33 recognizes a protein called GPC3 that is found on the hepatocellular carcinoma the patient has. The specific CAR we are making is called GPC3-CAR. To make this CAR more effective, we also added a gene encoding protein called IL15. This protein helps CAR T cells grow better and stay in the blood longer so that they may kill tumors better. The mixture of GPC3-CAR and IL15 killed tumor cells better in the laboratory when compared with CAR T cells that did not have IL 15. This study will test T cells that we have made with CATCH T cells in patients with GPC3-positive solid tumors such as the ones participating in this study. T cells made to carry a gene called iCasp9 can be killed when they encounter a specific drug called AP1903. The investigators will insert the iCasp9 and IL15 together into the T cells using a virus that has been made for this study. The drug (AP1903) is an experimental drug that has been tested in humans with no bad side-effects. The investigators will use this drug to kill the T cells if necessary due to side effects. This study will test T cells genetically engineered with a GPC3-CAR and IL15 (CATCH T cells) in patients with GPC3-positive solid tumors. The CATCH T cells are an investigational product not approved by the Food and Drug Administration. The purpose of this study is to find the biggest dose of CATCH T cells that is safe , to see how long they last in the body, to learn what the side effects are and to see if the CATCH T cells will help people with GPC3-positive solid tumors.

Conditions

Malignant Rhabdoid Tumor; Rhabdomyosarcoma; Liposarcoma; Embryonal Sarcoma of the Liver; Liver Cell Carcinoma; Solid Tumor; Wilms Tumor; Yolk Sac Tumor

Keywords

15.GPC3-CAR T cells; GPC3; Glypican; Liver cancer; Solid Tumor

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 dose-limiting toxicity is any Grade 3 or Grade 4 nonhematologic toxicity that fails to return to Grade 2 within 72 hours; Grade 2 to 4 allergic reaction to CAR T cell infusion; Grade 4 hematologic toxicity that persists for 28 days or greater; Grade 3 and 4 expected reactions due to CRS and neurotoxicity are seen with the use of CAR-based immunotherapy. Grade 3 cytokine release syndrome (CRS) infusion reactions and neurologic toxicity will only be reported to the FDA if they fail to return to Grade 1 within 7 days. Grade 4 CRS and neurologic toxicities will be reported to the FDA in an expedited fashion.

  4 weeks

Secondary Outcomes (2)

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

  4 weeks

• Median T cell persistence

  15 years

Study Arms (1)

CATCH T cells

EXPERIMENTAL

GPC3-CAR and the IL15 (CATCH T cells) will be administered to patients with GPC3-positive solid tumors.

Genetic: CATCH T cells

Interventions

CATCH T cells GENETIC

Four different dosing schedules will be evaluated. Three to six patients will be evaluated on each dosing schedule. The following dose levels will be evaluated: DL1: 3x10\^7/m2 DL2: 1x10\^8/m2 DL3: 3x10\^8/m2 DL4: 1x10\^9/m2 The doses are calculated according to the actual number of GPC3-CAR transduced T cells.

Also known as: GPC3-CAR T cells

CATCH T cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapsed or refractory 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 ≥18 years
• Lansky or Karnofsky score ≥60%
• Life expectancy ≥16 weeks
• Barcelona Clinic Liver Cancer Stage A, B or C (for patients with hepatocellular carcinoma only)
• 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

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)
• Treatment Eligibility
• Age ≥ 18 years
• Barcelona Clinic Liver Cancer Stage A, B or C (for patients with hepatocellular carcinoma only)
• Life expectancy of ≥ 12 weeks
• Lansky or Karnofsky score ≥ 60%
• Child-Pugh-Turcotte score \< 7 (for patients with hepatocellular carcinoma only)
• Adequate organ function:
• Creatinine clearance as estimated by Cockcroft Gault or Schwartz ≥ 60 ml/min
• serum AST\< 5 times ULN
• total bilirubin \< 3 times ULN for age
• INR ≤1.7 (for patients with hepatocellular carcinoma only)

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator

Study Sites (1)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Wilms Tumor; Rhabdoid Tumor; Endodermal Sinus Tumor; Rhabdomyosarcoma; Liposarcoma; Liver Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Neoplasms, Complex and Mixed; 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

• Tannaz Armaghany, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

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: Assistant Professor

Study Record Dates

• First Submitted: October 21, 2021
• First Posted: November 2, 2021
• Study Start: June 17, 2021
• Primary Completion: January 13, 2025
• Study Completion (Estimated): December 1, 2040
• Last Updated: March 6, 2026

Record last verified: 2026-03

Locations

US (1)