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

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This study enrolls patients who have GPC3-positive solid tumors currently. Patients may be considered if the cancer has come back, has not gone away after standard treatment or the patient cannot receive standard treatment. This research study uses special immune system cells called GAP T cells, a new experimental treatment. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise, but have not been strong enough to cure most patients. Investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. In preclinical studies, the investigators made several genes called a chimeric antigen receptor (CAR), from an antibody called GC33 that recognizes glypican-3, a proteoglycan found on solid tumors including pediatric liver cancers (GPC3-CAR). This study will test T cells genetically engineered with a GPC3-CAR (GAP T cells) in patients with GPC3-positive solid tumors (currently only enrolling liver tumors). The GAP T cells are an investigational product not approved by the Food and Drug Administration. The purpose of this study is to find the biggest dose of GAP T cells that is safe, to see how long they last in the body, to learn what the side effects are and to see if the GAP T cells will help people with GPC3-positive solid tumors. This study enrolls patients who have GPC3-positive solid tumors (currently only enrolling liver tumors).

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.

What data supports the effectiveness of this treatment for liver cancer?

CAR T-cell therapy, which is part of the treatment being studied, has shown success in treating blood cancers and is being explored for solid tumors like liver cancer. Additionally, a study on a similar therapy using T cells showed promising results in liver cancer patients, with most patients remaining disease-free after treatment. ^{1 2 3 4 5}

Is CAR T-cell therapy safe for humans?

CAR T-cell therapy has been shown to be generally safe in humans, even in those with prior hepatitis B infection, with no significant differences in side effects like cytokine release syndrome (a condition where the immune system is overly activated) and neurologic toxicity. In animal studies, CAR T-cell therapy was also found to be safe, although some liver changes were noted, suggesting the need for further monitoring. ^{3 4 5 6 7}

How is CAR T-Cell Therapy for Liver Cancer different from other treatments?

CAR T-Cell Therapy for Liver Cancer is unique because it uses specially engineered immune cells (T-cells) to target and kill cancer cells, which is different from traditional treatments like chemotherapy that attack all rapidly dividing cells. This therapy is designed to specifically recognize and attack liver cancer cells, potentially offering a more targeted approach with fewer side effects. ^{2 4 5 8 9}

Research Team

Andras A Heczey, M.D.

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Clinical Safety and Efficacy of Locoregional Therapy Combined with Adoptive Transfer of Allogeneic γδ T Cells for Advanced Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. [2022]

2. Singapore pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor-engineered T-cell therapy for liver cancer. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

A phase I clinical trial utilizing autologous tumor-infiltrating lymphocytes in patients with primary hepatocellular carcinoma. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Natural Killer Cells and T Cells in Hepatocellular Carcinoma and Viral Hepatitis: Current Status and Perspectives for Future Immunotherapeutic Approaches. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor-Glypican-3 T-Cell Therapy for Advanced Hepatocellular Carcinoma: Results of Phase I Trials. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of chimeric antigen receptor (CAR)-T-cell therapy in persons with advanced B-cell cancers and hepatitis B virus-infection. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

The safety of CAR-T cells and PD-1 antibody combination on an experimental model. [2023]

8. England pubmed.ncbi.nlm.nih.gov

HGF-Based CAR-T Cells Target Hepatocellular Carcinoma Cells That Express High Levels of c-Met. [2023]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Engineering for Success: Approaches to Improve Chimeric Antigen Receptor T Cell Therapy for Solid Tumors. [2021]