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Engineered immune cells take on Hard-to-Treat cancers

NCT ID NCT05003895

What the study statuses mean

This study's is highlighted.

Recruitment status, easiest to join first

Recruiting now This study
This trial is taking on new participants right now.
Not yet recruiting
Registered, but not yet taking participants.
By invitation only
Not open to general applications. Only people the study team invites can take part.
Paused
Paused for now. It may or may not start again.
Ongoing
Running, but no longer taking on new participants.
Completed
The trial has finished. Results may not be published yet.
Stopped early
Stopped early, before it reached the end. That can be for many reasons, including safety.
Cancelled
Cancelled before anyone took part.

Expanded access (not trials)

Expanded access
Not a trial. This treatment can be requested outside a study, case by case, for people who qualify.
Expanded access (paused)
Not a trial. The treatment can normally be requested outside a study, but is unavailable right now.
Expanded access (ended)
Not a trial. The treatment could once be requested outside a study, but no longer can.
Approved
The treatment has been approved, so it is available normally rather than through this programme.

When the status isn't known

Details not published
The full record has not been published yet, so there is little to show here.
Status unknown
This status has not been confirmed recently, so it may be out of date.

First seen Jun 25, 2026 · Last updated Jun 27, 2026 · Updated 1 time

Summary

This early-stage trial tests a new treatment where a patient's own immune cells are modified in a lab to better recognize and attack cancer cells that carry a protein called GPC3. The study includes 38 adults with advanced solid tumors, such as liver cancer, who have not responded to prior treatments. Participants receive chemotherapy followed by a single infusion of the modified cells and are monitored closely for safety and any tumor shrinkage.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance
CAR-T cells targeting GPC3
What this could lead to
If successful, this could point toward a new treatment option for advanced liver cancer and other solid tumors that express GPC3.
What could go wrong
This is an early Phase 1 trial with only 38 participants, so safety and dosing are still being tested. The treatment may not shrink tumors or could cause serious side effects.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 1

The first testing in people. Mainly checks safety and dose, usually in a small group.

Participants

About 38 people

The number the study aims to enrol. It can still change while the study runs.

Started

Dec 2021

Expected to finish

Dec 2027

An estimate. End dates often move.

Lead sponsor

A government research agency

The lead sponsor is the US National Institutes of Health.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 to 120 years

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

* INCLUSION CRITERIA: * 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 OR --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 If no cirrhosis: bilirubin should be \<= 1.5 x ULN ALT or AST: \<= 5 x ULN. Creatinine OR Measured or calculated creatinine clearance (CrCl) (eGFR may also be used in place of CrCl) (A): \< 1.5x institution upper limit of normal OR \>= 50 mL/min/1.73 m\^2 for participant with creatinine levels, \>= 1.5 X institutional ULN ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal. (A)Creatinine clearance (CrCl) or eGFR should be calculated per institutional standard. * Normal cardiac ejection fraction (\>= 50% by echocardiogram) and no evidence of hemodynamically significant pericardial effusion as determined by an echocardiogram within 4 weeks before treatment initiation. * Room air oxygen saturation of 92% or greater. * Treatment-related toxicities must be resolved to \<= grade 1. * For participants with brain metastases: Participants with \<=3 (three or fewer) brain metastases that have been treated with surgery or stereotactic radiosurgery or other form of treatment are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month before protocol treatment. * The study drugs are harmful to developing human fetus. For this reason, women of childbearing potential must agree to use highly effective contraception (hormonal, intrauterine device (IUD), abstinence, surgical sterilization) at the study entry and up to 12 months after the last dose of combined chemotherapy. Men must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and up to 4 months after the last dose of study drugs. We also recommend men with partners of childbearing potential ask their partners to be on highly effective birth control (hormonal, IUD, surgical sterilization). Men must not freeze or donate sperm within the same period. * HBV infected participants must be on antivirals and have HBV DNA \< 100IU/mL. HCV infected participants can be enrolled with close HCV RNA level monitoring. * Participants must be able to understand and be willing to sign a written informed consent. * For participants that do not have a legally authorized representative in place, one must be identified before study treatment starts Exclusion Criteria * 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.

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Conditions

The condition(s) this trial relates to.

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

How to take part

Only the study team decides who joins. These are the ways to reach them.

  1. The places running it

    1 site. The list below names each one and where it is.

  2. The official record

    ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

    Open the record ↗

  3. A doctor treating you

    A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Locations

  • National Institutes of Health Clinical Center

    RECRUITING

    Bethesda, Maryland, 20892, United States

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