Immunotherapy for Solid Tumor Malignancies in Pediatrics Using Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor T Cells

NCT07148050 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IMPACT
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase 1, open-label, non-randomized study will enroll pediatric and young adult subjects with relapsed or refractory non-central nervous system (CNS) malignant solid tumors expressing glypican-3 (GPC3) to examine the safety, feasibility, and efficacy of administering T cell products derived from peripheral blood mononuclear cells (PBMC) that have been genetically modified to co-express a GPC3-specific chimeric antigen receptor (CAR), interleukin (IL)-15 and IL-21 as well as the inducible caspase 9 (iC9) suicide gene (SC-CAR.GPC3xIL15.21 T cells). A child or young adult meeting all eligibility criteria and meeting none of the exclusion criteria will have a blood sample collected, which will be used to bioengineer the CAR T cells targeting their tumor.

Conditions

Malignant Rhabdoid Tumor; Liposarcoma; Rhabdomyosarcoma; Embryonal Sarcoma of Liver; Wilms Tumor; Hepatocellular Carcinoma; Hepatoblastoma; Solid Tumor (Excluding CNS); Liver Cell Carcinoma; Yolk Sac Tumor

Keywords

CAR T cell; Pediatric; Young Adult; Non-CNS Tumor; Liver Cancer; Solid Tumor; GPC3; Glypican

Outcome Measures

Primary Outcomes (2)

• The number of successfully manufactured SC-CAR.GPC3xIL15.21 T cell products will be assessed

  The number of successfully manufactured products will be measured

  28 days

• Establish the safety, defined by adverse events of SC-CAR.GPC3xIL15.21 T cells.

  Type, frequency, severity, and duration of adverse events will be tabulated and summarized

  28 days

Secondary Outcomes (2)

• Estimate the maximum tolerated dose (MTD) or biologically effective dose and dose limiting toxicities (DLT), and describe the full toxicity profile of SC-CAR.GPC3xIL15.21 T cells.

  28 days

• To estimate anti-tumor responses by measuring changes in tumor burden using disease-specific evaluations following SC-CAR.GPC3xIL15.21 T cells.

  42 days

Study Arms (1)

SC-CAR.GPC3xIL15.21 T cells

EXPERIMENTAL

Autologous SC-CAR.GPC3xIL15.21 T cell product will be infused as a single infusion.

Biological: SC-CAR.GPC3xIL15.21 CAR T cells

Interventions

SC-CAR.GPC3xIL15.21 CAR T cells BIOLOGICAL

Autologous SC-CAR.GPC3xIL15.21 T cell products infusion

SC-CAR.GPC3xIL15.21 T cells

Eligibility Criteria

• Age: 1 Year - 26 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of a solid tumor expressing GPC3
• Lansky or Karnofsky score of \>=60%
• Life expectancy of \>16 weeks
• Informed consent explained to, understood by and signed by patient/guardian.
• For patients with hepatocellular carcinoma only:
• Barcelona Liver Cancer Stage A, B or C
• Child-Pugh Turcotte Score \<7

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 for 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
• Lansky or Karnofsky score of \>=60%
• Life expectancy of \>16 weeks
• Informed consent explained to, understood by and signed by patient/guardian.
• Adequate organ function
• Adequate laboratory values
• Refractory or relapsed disease after treatment with up- front therapy and at least one salvage treatment cycle
• Recovered from acute toxic effects of all prior chemotherapy and investigational agents before entering this study
• Sexually active patients must be willing to utilize one of the more effective birth control methods for 12 months after the T-cell infusion.
• Informed consent explained to, understood by and signed by patient/guardian.
• For patients with hepatocellular carcinoma only:

Sponsors & Collaborators

• Seattle Children's Hospital: lead

Study Sites (1)

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Rhabdoid Tumor; Endodermal Sinus Tumor; Liposarcoma; Rhabdomyosarcoma; Wilms Tumor; Hepatoblastoma; 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; Mesonephroma; Neoplasms, Germ Cell and Embryonal; Neoplasms, Adipose Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Myosarcoma; Neoplasms, Muscle Tissue; 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

Study Officials

• Colleen Annesley, MD

  Seattle Children's Hospital

  STUDY DIRECTOR

• Corinne Summers, MD

  Seattle Children's Hospital

  STUDY DIRECTOR

Central Study Contacts

Michelle Choe, MD

CONTACT

206-987-2106; immunotherapy@seattlechildrens.org

Andras Heczey, MD

CONTACT

Andras.Heczey@seattlechildrens.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: Medical Director - Seattle Children's Therapeutic

Study Record Dates

• First Submitted: August 22, 2025
• First Posted: August 29, 2025
• Study Start: December 22, 2025
• Primary Completion (Estimated): April 22, 2029
• Study Completion (Estimated): April 22, 2044
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)