CATCH T Cells for Solid Cancers

Overseen By Tannaz Armaghany

Age: 18+

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 week

27 Participants Needed

Trial Summary

What is the purpose of this trial?

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 CATCH 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 we can put a new gene (a tiny part of what makes-up DNA and carriesa person's traits) into T cells that will make them recognize cancer cells and kill them . In the lab, we made several genes called a chimeric antigen receptor (CAR), from an antibody called GC33. The antibody GC33 recognizes a protein called GPC3 that is found on the hepatocellular carcinoma the patient has. The specific CAR we are making is called GPC3-CAR. To make this CAR more effective, we also added a gene encoding protein called IL15. This protein helps CAR T cells grow better and stay in the blood longer so that they may kill tumors better. The mixture of GPC3-CAR and IL15 killed tumor cells better in the laboratory when compared with CAR T cells that did not have IL 15. This study will test T cells that we have made with CATCH T cells in patients with GPC3-positive solid tumors such as the ones participating in this study. T cells made to carry a gene called iCasp9 can be killed when they encounter a specific drug called AP1903. The investigators will insert the iCasp9 and IL15 together into the T cells using a virus that has been made for this study. The drug (AP1903) is an experimental drug that has been tested in humans with no bad side-effects. The investigators will use this drug to kill the T cells if necessary due to side effects. This study will test T cells genetically engineered with a GPC3-CAR and IL15 (CATCH T cells) in patients with GPC3-positive solid tumors. The CATCH 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 CATCH 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 CATCH T cells will help people with GPC3-positive solid 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 you must stop systemic steroid treatment at least 24 hours before the CAR T cell infusion.

What data supports the effectiveness of the CATCH T cells treatment for solid cancers?

Research shows that T cells engineered to target glypican-3 (GPC3), a protein found on some solid tumors, can effectively kill cancer cells in lab studies and animal models. These engineered T cells have shown promising results in reducing tumor size and improving immune response in various solid tumors, suggesting potential effectiveness for treating GPC3-positive cancers. ^{1 2 3 4 5}

Is the CATCH T cell treatment generally safe for humans?

Research on similar treatments, like GPC3-CAR T cells, shows they can be effective against certain tumors without causing harmful side effects in animal models. However, it's important to note that these studies are primarily in mice, and human safety data is still limited. ^{1 2 5 6 7}

What makes the CATCH T cells treatment unique for solid cancers?

CATCH T cells are unique because they are engineered to target glypican-3 (GPC3), a protein found on certain solid tumors, and are enhanced with IL-15 to improve their effectiveness. This approach aims to overcome the challenges of treating solid tumors by boosting the T cells' ability to attack cancer cells and persist in the body, which is not typically achieved with standard CAR T cell therapies. ^{1 2 3 5 8}

Research Team

Tannaz Armaghany

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

Adults with certain solid tumors like liver cancer, who have tried standard treatments without success or can't receive them. They must be in relatively good health with a life expectancy of at least 12 weeks and adequate organ function. Pregnant individuals, those with HIV, active infections (except Hepatitis B/C), or history of organ transplant cannot participate.

Inclusion Criteria

I can care for myself but may need occasional help.

My platelet count is above 25,000, or I can receive a transfusion to reach it.

I can care for myself but may need occasional help.

Exclusion Criteria

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

You have been diagnosed with HIV.

I do not have any active infections, except possibly Hepatitis B or C.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Lymphodepletion Chemotherapy

Participants receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine for 3 days before T-cell infusion

1 week

3 visits (in-person)

Treatment

Participants receive CATCH T cells infusion 48 to 72 hours after completing chemotherapy

1 week

1 visit (in-person)

Follow-up

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

15 years

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

Treatment Details

Interventions

• CATCH T cells

Trial Overview The trial is testing CATCH T cells, which are the patient's own immune cells genetically modified to target and kill cancer cells by recognizing a protein called GPC3 on tumor surfaces. The study aims to determine the highest safe dose, how long these cells last in the body, their side effects, and effectiveness against GPC3-positive tumors.

Participant Groups

Group I: CATCH T cells Experimental Treatment 1 Intervention

GPC3-CAR and the IL15 (CATCH T cells) 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 Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

Findings from Research

T cells engineered with GPC3-specific CARs demonstrated strong cytotoxic effects against various solid tumors, including hepatocellular carcinoma and malignant rhabdoid tumors, indicating their potential as an effective treatment option.

Among the different CAR constructs tested, the GBBz CAR showed superior T cell expansion and a Th1-biased cytokine profile, suggesting it may be the most promising candidate for further clinical development in treating GPC3-positive solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Redirecting T Cells to Glypican-3 with 4-1BB Zeta Chimeric Antigen Receptors Results in Th1 Polarization and Potent Antitumor Activity. Li, W., Guo, L., Rathi, P., et al.[2022]

The study engineered CAR-T cells that can express IL-12, which significantly enhances their ability to target and destroy GPC3+ tumor cells, showing improved efficacy in both laboratory and animal models.

Inducible IL-12 expression not only boosts the antitumor response but also reduces regulatory T cell infiltration, suggesting a safer profile for CAR-T therapy, making it a promising option for patients who cannot undergo traditional lymphodepletion chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Armored Inducible Expression of IL-12 Enhances Antitumor Activity of Glypican-3-Targeted Chimeric Antigen Receptor-Engineered T Cells in Hepatocellular Carcinoma. Liu, Y., Di, S., Shi, B., et al.[2020]

Glypican 3 (GPC3) is expressed in 66.3% of lung squamous cell carcinoma (LSCC) samples, making it a promising target for therapy, as it is rarely found in normal lung tissues.

CARgpc3 T cells, engineered to target GPC3, showed strong antitumor activity by effectively eliminating GPC3-positive LSCC cells in vitro and in two xenograft models, suggesting they could be a novel treatment option for LSCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy using T lymphocytes redirected to glypican-3 for the treatment of lung squamous cell carcinoma. Li, K., Pan, X., Bi, Y., et al.[2020]

ERY974, a bispecific T cell-redirecting antibody targeting GPC3 and CD3, has shown strong efficacy in killing tumors expressing GPC3, even in nonimmunogenic tumors that are typically hard to treat with standard immunotherapies.

Toxicology studies in cynomolgus monkeys indicated that while ERY974 caused transient cytokine elevation, it was manageable and reversible, with no evidence of organ toxicity, supporting its safety for potential clinical use in GPC3-positive solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An anti-glypican 3/CD3 bispecific T cell-redirecting antibody for treatment of solid tumors. Ishiguro, T., Sano, Y., Komatsu, SI., et al.[2018]

The fourth-generation GPC3-targeted CAR-T cells (GPC3-BBZ-7×19) demonstrated enhanced proliferation and chemotactic abilities compared to second-generation CAR-T cells, indicating a potentially more effective treatment for hepatocellular carcinoma (HCC).

In vivo studies showed that GPC3-BBZ-7×19 CAR-T cells significantly eliminated GPC3-positive HCC tumors in immunodeficient mice, suggesting they could provide a durable and effective therapeutic option for HCC in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Construction and function of Glypican-3-targeted fourth-generation chimeric antigen receptor T cells (secreting IL-7 and CCL19)]. Huang, W., Liu, Y., Hu, Y., et al.[2020]

CAR-T cells targeting glypican-1 (GPC1) demonstrated strong antitumor effects in both xenogeneic and syngeneic mouse models, indicating their potential effectiveness against solid tumors.

The use of murine CAR-T cells not only targeted GPC1 but also enhanced the body's own T cell responses against other tumor antigens, showing a mechanism of antigen-spreading and no adverse effects when combined with anti-PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GPC1 specific CAR-T cells eradicate established solid tumor without adverse effects and synergize with anti-PD-1 Ab. Kato, D., Yaguchi, T., Iwata, T., et al.[2021]

Dual-targeted CAR-T cells that target both GPC3 and ASGR1 showed no cytotoxicity to tumor cells lacking GPC3, suggesting a reduced risk of on-target, off-tumor toxicity while effectively targeting hepatocellular carcinoma (HCC).

These dual-targeted CAR-T cells demonstrated enhanced anti-tumor activity, including higher cytokine secretion and proliferation, and effectively suppressed the growth of GPC3+ASGR1+ HCC tumors in xenograft models, outperforming single-targeted CAR-T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of T cells carrying two complementary chimeric antigen receptors against glypican-3 and asialoglycoprotein receptor 1 for the treatment of hepatocellular carcinoma. Chen, C., Li, K., Jiang, H., et al.[2017]

The study developed CAR T cells targeting glypican-1 (GPC1) in pancreatic cancer, using dromedary camel VHH nanobodies to enhance T-cell activity against tumors with low antigen density.

Optimizing the CAR structure with a rigid IgG4 hinge and CD28 transmembrane domain improved T-cell signaling and led to significant tumor regression in female mice, highlighting a promising approach for CAR T cell therapy in solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The IgG4 hinge with CD28 transmembrane domain improves VHH-based CAR T cells targeting a membrane-distal epitope of GPC1 in pancreatic cancer. Li, N., Quan, A., Li, D., et al.[2023]

References

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

Redirecting T Cells to Glypican-3 with 4-1BB Zeta Chimeric Antigen Receptors Results in Th1 Polarization and Potent Antitumor Activity. [2022]

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

Armored Inducible Expression of IL-12 Enhances Antitumor Activity of Glypican-3-Targeted Chimeric Antigen Receptor-Engineered T Cells in Hepatocellular Carcinoma. [2020]

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

Adoptive immunotherapy using T lymphocytes redirected to glypican-3 for the treatment of lung squamous cell carcinoma. [2020]

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

An anti-glypican 3/CD3 bispecific T cell-redirecting antibody for treatment of solid tumors. [2018]

5. China pubmed.ncbi.nlm.nih.gov

[Construction and function of Glypican-3-targeted fourth-generation chimeric antigen receptor T cells (secreting IL-7 and CCL19)]. [2020]

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

GPC1 specific CAR-T cells eradicate established solid tumor without adverse effects and synergize with anti-PD-1 Ab. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Development of T cells carrying two complementary chimeric antigen receptors against glypican-3 and asialoglycoprotein receptor 1 for the treatment of hepatocellular carcinoma. [2017]

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

The IgG4 hinge with CD28 transmembrane domain improves VHH-based CAR T cells targeting a membrane-distal epitope of GPC1 in pancreatic cancer. [2023]