CAR T-Cell Therapy for Liver Cancer

(GAP Trial)

Overseen By Ramy Sweidan

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Systemic steroids

Disqualifiers: HIV, Organ transplant, Uncontrolled infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called GAP T cells (a type of CAR T-cell therapy) to determine if they can fight liver cancer by targeting specific proteins on cancer cells. The trial aims to find the safest dose of these specially engineered immune cells and understand their effects on the body. It seeks participants whose liver cancer has either returned or not responded to standard treatments. This trial might suit those with GPC3-positive liver cancer (a type of protein found on some tumors) and who are between the ages of 1 and 21. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that systemic steroid treatment must be adjusted or stopped at least 24 hours before the CAR T cell infusion. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that GAP T cells, part of a new treatment being tested for liver cancer, have shown promise in earlier studies. These studies have targeted a protein called glypican-3 (GPC3), found on many liver tumors. The advantage is that GPC3 is specific to cancer cells, potentially reducing side effects from mistakenly targeting healthy cells.

GAP T cells remain experimental and lack FDA approval. This treatment harnesses the body's immune system to combat cancer. Similar treatments using CAR T cells have received approval for other cancer types, with patients experiencing significant tumor reductions.

As this treatment is in early testing stages, researchers aim to find the safest dose and understand potential side effects. The focus remains on ensuring the treatment is well-tolerated and effective in targeting cancer cells. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for liver cancer, such as surgery, radiation, and chemotherapy, GAP T cells offer a novel approach by using genetically engineered immune cells. Researchers are excited about GAP T cells because they are designed to target GPC3-positive solid tumors specifically, which may enhance precision in attacking cancer cells while minimizing harm to healthy tissue. This treatment also involves a unique mechanism of action, involving the genetic modification of T cells to better recognize and destroy cancer cells, potentially leading to more effective and personalized treatment outcomes.

What evidence suggests that this trial's treatments could be effective for liver cancer?

Research has shown that GAP T cells, a type of CAR T-cell therapy, could be effective against liver cancer. These cells are designed to target glypican-3 (GPC3), a protein often found on liver cancer cells. Studies suggest that targeting GPC3 can help avoid damage to healthy cells. In early tests, CAR T cells demonstrated a strong ability to fight tumors and grow in the body, attacking cancer cells. In this trial, participants will receive GAP T cells along with lymphodepleting chemotherapy using Cytoxan and Fludarabine. While these results are encouraging, further research is needed to confirm their effectiveness in people. ^{1 2 4 5 6}

Who Is on the Research Team?

David Steffin, M.D.

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 1 to 21 with GPC3-positive solid liver tumors that have either returned after treatment, haven't responded to standard treatments, or can't be treated conventionally. Participants need a reasonable life expectancy and good performance status, but those with organ transplants, HIV, active infections (except certain hepatitis), severe reactions to Cytoxan or Fludara, or allergies to murine proteins are excluded.

Inclusion Criteria

I can do most activities but may need help.

I am mostly able to carry out daily activities.

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), absolute neutrophil count > 500/microliter, platelet count > 25,000/microliter (can be transfused), Hgb ≥7.0 g/dl (can be transfused), pulse oximetry >90% on room air, 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. Patient/guardian given copy of informed consent

Exclusion Criteria

I am allergic to mouse protein products or have human anti-mouse antibodies.

I have had an organ transplant.

I am not on high doses of steroids or can stop them 24 hours before CAR T cell therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Lymphodepletion Chemotherapy

Participants receive cyclophosphamide and fludarabine for 3 days to decrease their own T cells before the infusion of GAP T cells.

1 week

3 visits (in-person)

Treatment

Participants receive the GAP T cells infusion 48 to 72 hours after completing chemotherapy.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including blood tests and tumor measurements.

15 years

Regular visits every 3 months for 1 year, every 6 months for 4 years, then annually for 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Cytoxan
• Fludara
• GAP T cells

Trial Overview The GAP clinical trial is testing a new therapy using GAP T cells—immune cells modified with a chimeric antigen receptor targeting glypican-3 on cancer cells. The study aims to determine the highest safe dose of these engineered T cells, their lifespan in the body, side effects they may cause, and their effectiveness against liver tumors.

How Is the Trial Designed?

Group I: GAP T cells + Fludarabine and Cytoxan Experimental Treatment 3 Interventions

GPC3-Car (GAP T cells) along with lymphodepleting chemotherapy (Cytoxan and Fludarabine) will be administered to patients with GPC3-positive solid tumors.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

The V Foundation

Collaborator

Trials

10

Recruited

320+

Cookies for Kids' Cancer

Collaborator

Trials

7

Recruited

360+

Curing Kids' Cancer Foundation

Collaborator

Trials

2

Recruited

20+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

Cancer Prevention Research Institute of Texas

Collaborator

Trials

55

Recruited

98,900+

Published Research Related to This Trial

In a Phase I clinical trial involving 15 patients with primary hepatocellular carcinoma (HCC), adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TIL) demonstrated low toxicity, with only mild flu-like symptoms reported after treatment.

After a median follow-up of 14 months, all patients were alive, and 80% showed no evidence of disease, suggesting that this immunotherapy could be an effective new treatment option for HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I clinical trial utilizing autologous tumor-infiltrating lymphocytes in patients with primary hepatocellular carcinoma. Jiang, SS., Tang, Y., Zhang, YJ., et al.[2018]

CAR T cells targeting CD19 have shown great success in treating blood cancers, but they struggle to achieve similar results in solid tumors due to several challenges.

Key obstacles for CAR T cell effectiveness in solid tumors include poor targeting to tumor sites, limited growth and survival of the cells, a suppressive tumor environment, and varying levels of target antigens on tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering for Success: Approaches to Improve Chimeric Antigen Receptor T Cell Therapy for Solid Tumors. Mata, M., Gottschalk, S.[2021]

In two phase I studies involving 13 patients with advanced GPC3+ hepatocellular carcinoma, CAR-GPC3 T-cell therapy showed an initial safety profile, with manageable side effects like fever and cytokine release syndrome, and no severe neurotoxicity reported.

The therapy demonstrated early signs of antitumor activity, with overall survival rates of 50.3% at 6 months and 42.0% at 1 year, along with two partial responses observed, suggesting potential efficacy in treating this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor-Glypican-3 T-Cell Therapy for Advanced Hepatocellular Carcinoma: Results of Phase I Trials. Shi, D., Shi, Y., Kaseb, AO., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8889910/

Glypican-3: A Novel and Promising Target for the ... CAR-T can effectively kill tumor cells with low expression of cell surface antigens, which will expand substantially in the body during treatment of patients.

2. ajmc.com ajmc.com/view/car-t-cells-improve-antitumor-activity-in-hepatocellular-carcinoma

CAR T Cells Improve Antitumor Activity in Hepatocellular ... In this study, investigators found that gene-edited CAR T cells with PD-1 deficiency have stronger antitumor activity than wild-type CAR T cells.

3. jnanobiotechnology.biomedcentral.com jnanobiotechnology.biomedcentral.com/articles/10.1186/s12951-025-03512-w

Advancing liver cancer treatment with dual-targeting CAR-T ... This dual-targeting strategy significantly improved CAR-T cell proliferation and persistence, as well as enhancing cytokine expression and anti-tumor activity ...

4. onclive.com onclive.com/view/gpc3-offers-highly-specific-target-in-hcc

GPC3 Offers Highly Specific Target in HCC Key Takeaways · GPC3 is a promising target for HCC treatment due to its cancer-specific expression, potentially reducing off-target toxicities.

5. imrpress.com imrpress.com/journal/FBL/29/7/10.31083/j.fbl2907268/htm

Exploring Glypican-3 as a Molecular Target in ... While liver transplantation patients have 5-year survival rates of 60% to 80%, recurrence remains a significant issue, affecting 10% to 20% of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04715191

NCT04715191 | Interleukin-15 and -21 Armored Glypican- ... The purpose of this study is to find the biggest dose of CARE T cells that is safe, to see how long they last in the body, to learn what the side effects are ...