GPC3 Targeted CAR-T Cell Therapy in Advanced GPC3 Expressing Solid Tumor Malignancies

NCT05003895 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 21003021-C-0030
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

Background: A new cancer treatment takes a person s own T cells, modifies them in a laboratory so they can better fight cancer cells, and then gives them back to the person. Researchers want to see if this treatment can help people with a certain types of cancer. Objective: To see if a personalized immune treatment, anti-GPC3 CAR-T cells, is safe. Eligibility: Adults aged 18 years and older who have Glypican-3 (GPC3) positive solid tumor malignancy. Design: Participants will be screened with the following: Blood and urine tests Medical history Physical exam Heart function tests Review of their symptoms and their ability to perform their normal activities Tumor biopsy Imaging scan of the chest, abdomen, and pelvis Participants will have leukapheresis. They may have an IV (intravenous catheter, a small tube put into an arm vein) inserted into each arm or get a central line. Blood will be removed. A machine will separate the white blood cells from their blood. The rest of their blood will be returned to them. Participants will be admitted to the hospital for about 2 weeks. They will get the chemotherapy drugs fludarabine and cyclophosphamide by IV for 3 days. Then they will receive the modified white blood cells by IV. Participants will have frequent blood draws. They will give blood and tumor samples for research. Participants will have follow-up visits for the next 15 years. Then they will be contacted by email or phone for the rest of their life. If their disease does not get worse after 5 years, they will continue to be invited to do imaging studies every 6 months.

Conditions

Hepatocellular Carcinoma; Hepatocellular Cancer; Metastatic Hepatocellular Carcinoma

Keywords

immuno therapy; Targeted Therapy; Leukapheresis; Gene Therapy

Outcome Measures

Primary Outcomes (1)

• To determine the safety and feasibility of T-cells, expressing a novel humanized anti-GPC3 chimeric antigen receptor, in participants with advanced solid tumor malignancy, expressing GPC3.

  Safety will be reported based on DLTs per dose level as well as reporting specific grades and types of toxicity encountered. Feasibility will be reported descriptively as the fraction of participants overall and per dose level who are able to receive sufficient CAR T cells as required for the specified dose level

  15 years

Secondary Outcomes (2)

• To determine the best overall response (BOR) rate according to Response Evaluation Criteria (by RECIST v 1.1) of treatment with T-cells, expressing anti-GPC3 chimeric antigen receptor in participants with advanced solid tumor malignancy expressi...

  every 2-month for the first year, every 3 month for the second year, every 4 month for the third year, and every 6 month afterward until disease progression

• To characterize overall survival (OS)

  death

Study Arms (2)

1/ Arm 1

EXPERIMENTAL

Escalating doses of CAR-T cells

Drug: Cyclophosphamide; Biological: CAR-T cell; Drug: Fludarabine

2/ Arm 2

EXPERIMENTAL

MTD of CAR-T cells

Drug: Cyclophosphamide; Biological: CAR-T cell; Drug: Fludarabine

Interventions

Cyclophosphamide DRUG

Daily x 3 doses on Day -3, -2, -1 300 mg/m2 IV infusion (200 mg/m\^2 in Dose Level -1)

1/ Arm 1; 2/ Arm 2

CAR-T cell BIOLOGICAL

Single infusion on Day 0

1/ Arm 1; 2/ Arm 2

Fludarabine DRUG

Daily x 2 doses on Day -2 and -1 30 mg/m\^2 IV infusion administered following cyclophosphamide

1/ Arm 1; 2/ Arm 2

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathological confirmation of HCC or other solid tumor malignancy by the NCI Laboratory of Pathology
• Participants must:
• have progressed on at least 1 prior line of treatment
• been intolerant of at least 1 prior line of treatment.
• Participants must have at least 1 focus of disease that is amenable to mandatory tumor biopsy prior to study treatment initiation to determine tumor GPC3 expression and be willing to undergo this. Ideally, the biopsied lesion should not be one of the target measurable lesions, although this can be up to the discretion of the investigators.
• Tumor must have GPC3 positivity of \>= 25% by immunohistochemistry on freshly collected biopsy
• Participants must have at least 1 measurable lesion by RECIST version 1.1
• Participants must have a disease that is not amenable to potentially curative resection, ablation, or transplantation.
• Age \>= 18 years.
• Performance status (ECOG) 0-1
• Participants must have adequate organ and marrow function as defined below:
• ANC: \>= 1,000/mcL
• Platelets: \>= 75,000/mcL
• Hemoglobin: \>= 8 g/dL
• total bilirubin: If cirrhosis present: Part of Child Pugh requirement

You may not qualify if:

• Prior systemic therapy, an investigational therapy, radiation, and/or surgery within 2 weeks prior to treatment initiation.
• Prior administration of anti-PD-1 or anti-PD-L1 antibodies or other agents that in the opinion of the PI can stimulate immune activity and interfere with an infusion of CAR-T cells within 8 weeks prior to treatment initiation.
• Child-Pugh class B or C liver function
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Note: Participants with a history of abnormal pulmonary function tests but stable obstructive or restrictive pulmonary disease may be eligible per PI discretion.
• Any form of primary immunodeficiency (e.g. severe combined immunodeficiency).
• HIV-positive participants are excluded because HIV causes complicated immune deficiency and study treatment can pose more risks for these participants.
• Participants receiving systemic steroids \>= 0.5 mg prednisone equivalent/kg/day. Steroid creams, ointments, and eye drops are allowed. Dose adjustment or discontinuation of medication must occur at least 24 hours prior to conditioning chemotherapy. Use of CART cell therapy in autoimmune diseases has the potential to be associated with serious safety risk. Given that this is an evolving area of research, caution should be exercised and any decision to include participants with autoimmune diseases should be made on a case-bycase basis.
• History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine.
• Hospitalization within 7 days prior to treatment initiation.
• Pregnant women are excluded from this study because study therapy can cause fetal harm. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with study therapy, breastfeeding should be discontinued if the mother is treated with study drugs.
• Participants who received live or attenuated vaccine or virus-based vaccine within 30 days before initiation of study therapy
• Participants with a history of seizure disorder
• Participants with an expected life expectancy of less than 3 months before initiation of study therapy.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

Cyclophosphamide; Immunotherapy, Adoptive; fludarabine

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Tim F Greten, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Donna Hrones, C.R.N.P.

CONTACT

(240) 858-3155; donna.mabry@nih.gov

Tim F Greten, M.D.

CONTACT

(240) 760-6114; gretentf@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2021
• First Posted: August 13, 2021
• Study Start: December 8, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 24, 2026

Record last verified: 2026-02-27

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. @@@@@@@@@@@@Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)