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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment using special immune cells called CATCH T cells (GPC3-CAR T cells) to help people with certain types of solid tumors. These cells are designed to find and kill cancer cells more effectively. The trial aims to determine the safest dose, understand how long these cells remain active in the body, and identify any potential side effects. It is suitable for individuals whose cancer has returned or hasn't responded to standard treatments, specifically those with GPC3-positive tumors. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

In a previous study, researchers found that Interleukin-15 (IL15) helps special cancer-fighting cells, called GPC3-CAR T cells, grow and remain active longer in the body, enhancing their ability to fight cancer. The study showed that these enhanced cells, known as CATCH T cells, which include both GPC3-CAR and IL15, were more effective at surviving and killing cancer cells. These findings suggest that this treatment could be effective against certain types of solid tumors.

A backup plan exists in case of side effects. The T cells are designed to be destroyed with a specific drug called AP1903, which has been tested in humans and found to be safe. This provides a safety net if the CATCH T cells cause any problems.

Since this is a Phase 1 trial, the main goal is to determine the safest dose of CATCH T cells, rather than focusing on their effectiveness against cancer. This phase involves close monitoring for safety, and such trials usually have fewer participants. Although CATCH T cells are experimental and not yet approved by the FDA, the study is designed to ensure participant safety while testing this promising treatment approach. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for solid cancers?

Researchers are excited about CATCH T cells because they offer a novel approach to fighting solid tumors. Unlike traditional treatments like chemotherapy or radiation, which can harm healthy cells, CATCH T cells are engineered to specifically target and attack cancer cells expressing the GPC3 protein. This precision targeting minimizes damage to surrounding healthy tissue, potentially reducing side effects. Additionally, these T cells include an IL15 component, which helps them survive and multiply, enhancing their ability to fight cancer more effectively.

What evidence suggests that CATCH T cells might be an effective treatment for GPC3-positive solid tumors?

Research has shown that CATCH T cells, designed to attack cancer cells, could be effective against certain solid tumors with the GPC3 protein. Studies have found that adding the protein IL15 to these T cells enhances their growth and survival in the body, potentially improving their tumor-destroying ability. In lab tests, CATCH T cells with IL15 demonstrated greater effectiveness in killing cancer cells than those without it. The antibody component, GC33, specifically targets a protein on some cancer cells, enhancing precision. Although human study data is limited, these early findings suggest that CATCH T cells could be a powerful new option for treating certain solid tumors. Participants in this trial will receive CATCH T cells to evaluate their effectiveness in treating GPC3-positive solid tumors. ^{1 2 3 4 6}

Who Is on the Research Team?

Tannaz Armaghany

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

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 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 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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11030543/

Interleukin-15-armored GPC3-CAR T cells for patients with ... Collectively, these results demonstrate that IL15 increases the expansion, intratumoral survival, and antitumor activity of GPC3-CAR T cells in patients.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04715191

NCT04715191 | Interleukin-15 and -21 Armored Glypican- ... This study will test T cells genetically engineered with a GPC3-CAR and IL15 plus IL21 (CARE T cells) in patients with GPC3-positive solid tumors.

3. trials.braintumor.org trials.braintumor.org/trials/NCT05103631

Interleukin-15 Armored Glypican 3-specific Chimeric Antigen ... 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 ...

4. aacrjournals.org aacrjournals.org/clincancerres/article/26/15/3979/82521/Chimeric-Antigen-Receptor-Glypican-3-T-Cell

Chimeric Antigen Receptor-Glypican-3 T-Cell Therapy for ... Our preclinical studies demonstrated the potential of chimeric antigen receptor (CAR)-glypican-3 (GPC3) T-cell therapy for hepatocellular carcinoma (HCC).

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10480529/

RUNX-3-expressing CAR T cells targeting glypican-3 in ... CAR T cells showed significant efficacy in treating hematologic malignancies but its application in solid tumors is still challenging. Earliest ...

6. singlecell.chee.uh.edu singlecell.chee.uh.edu/wp-content/uploads/2024/12/s41586-024-08261-8-1.pdf

Interleukin-15-armoured GPC3 CAR T cells for patients with ... Collectively, these results demonstrate that IL-15 increases the expansion, intratumoural survival and antitumour activity of GPC3 CAR T cells in patients.