Cytokine Armored GPC3 Specific Chimeric Antigen Receptor Expressing T-cells in Adults With Solid Tumors

NCT07224568 | Not Yet Recruiting Phase 1 DMC FDA Drug

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

Brief Summary

This Phase 1, open-label, non-randomized study will enroll 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). An adult participant 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

Solid Tumor (Excluding CNS); Hepatocellular Carcinoma; Liver Cell Carcinoma; Liposarcoma; Yolk Sac Tumor; Rhabdomyosarcoma

Keywords

CAR T cell; 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 proportion of SC-CAR.GPC3xIL15.21 T cell products that are approved for release after up to 2 grow attempts will be measured.

  28 days

• To determine the safety of escalating doses of an intravenous injection of SC-CAR.GPC3xIL15.21 T cells in adults with relapsed or refractory GPC3-positive solid tumors after lymphodepleting chemotherapy based on frequency of adverse events based on CTCAE

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

  42 days

Secondary Outcomes (2)

• To determine the maximum tolerated dose (MTD) of SC-CAR.GPC3xIL15.21 T cells in treating patients with GPC3-positive solid tumors after lymphodepleting chemotherapy.

  42 days

• To assess the response rate in patients with relapsed or refractory GPC3-positive solid tumors infused with 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 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: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of a solid tumor expressing GPC3
• Karnofsky score of \>=60%
• Life expectancy of \>16 weeks
• Informed consent explained to, understood by and signed by participant or participant's legally authorized representative
• 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
• 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 3 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)

Fred Hutch Cancer Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

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

Study Officials

• Colleen Annesley

  Seattle Children's Hospital

  STUDY DIRECTOR

• Corinne Summers

  Seattle Children's Hospital

  STUDY DIRECTOR

Central Study Contacts

Gentry King, MD

CONTACT

206-606-1024; hutchdoc@fredhutch.org; gking@fredhutch.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 Therapeutics

Study Record Dates

• First Submitted: October 28, 2025
• First Posted: November 4, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2045
• Last Updated: November 4, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)