21 Participants Needed

Immunotherapy for Cancer

AH
DS
Overseen ByDavid Steffin, MD
Age: < 65
Sex: Any
Trial Phase: Phase 1
Sponsor: Baylor College of Medicine
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

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. In order to get them to kill cancers more effectively, in the laboratory, the study team inserted a new gene called a chimeric antigen receptor (CAR) into T cells that makes them recognize cancer cells and kill them. When inserted, this new CAR T cell can specifically recognize a protein found on solid tumors, called glypican-3 (GPC3). To make this GPC3-CAR more effective, the study team also added two genes called IL15 and IL21 that help CAR T cells grow better and stay in the blood longer so that they may kill tumors better. When the study team did this in the laboratory, they found that this mixture of GPC3-CAR,IL15 and IL21 killed tumor cells better when compared with CAR T cells that did not have IL15 plus IL21 in the laboratory. This study will use those cells, which are called 21.15.GPC3-CAR T cells, to treat patients with solid tumors that have GPC3 on their surface. The study team also wanted to make sure that they could stop the 21.15.GPC3-CAR T cells from growing in the blood should there be any bad side effects. In order to do so, they inserted a gene called iCasp9 into the FAST-CAR T cells. This allows us the elimination of 21.15.GPC3-CAR T cells in the blood when the gene comes into contact with a medication called AP1903. The drug (AP1903) is an experimental drug that has been tested in humans with no bad side-effects. This drug will only be used to kill the T cells if necessary due to side effects . The study team has treated patients with T cells that include GPC3. Patients have also been treated with IL-21 and with IL-15. Patients have not been treated with a combination of T cells that contain GPC3, IL-21 and IL-15. To summarize, this study will test the effect of 21.15.GPC3-CAR T cells in patients with solid tumors that express GPC3 on their surface. The 21.15.GPC3-CAR T cells are an investigational product not yet approved by the Food and Drug Administration.

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 treatment 21.15.GPC3-CAR T cells for cancer?

Research shows that GPC3-CAR T cells, which are a type of immunotherapy, can effectively target and destroy cancer cells that express a protein called glypican-3 (GPC3). These cells have shown promise in treating liver cancer and lung cancer by reducing tumor size and improving immune response in studies.12345

Is immunotherapy with 21.15.GPC3-CAR T cells generally safe for humans?

CAR T-cell therapy, including those targeting glypican-3 (GPC3), can cause side effects like cytokine release syndrome (a severe immune reaction) and neurologic toxicity. However, studies suggest that modifications, such as inducible IL-12 expression, may enhance safety by reducing potential side effects while maintaining antitumor activity.23467

How does the 21.15.GPC3-CAR T cell treatment differ from other cancer treatments?

The 21.15.GPC3-CAR T cell treatment is unique because it uses specially engineered T cells to target glypican-3 (GPC3), a protein found on certain cancer cells, enhancing the immune system's ability to attack these cells. This treatment also includes modifications to improve T cell persistence and activity in the challenging environment of solid tumors, making it a promising option for cancers that express GPC3.12348

Research Team

AH

Andras Heczey, MD

Principal Investigator

Baylor College of Medicine

DS

David Steffin, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

Adults with certain solid tumors that test positive for a protein called GPC3 can join this trial. They should be at least 21 years old, have a reasonable quality of life score, and expect to live at least another 16 weeks. People with liver cancer must meet specific criteria related to their disease stage and liver function.

Inclusion Criteria

I am 21 years old or older.
Child-Pugh-Turcotte score <7 (for patients with hepatocellular carcinoma only)
Informed consent explained to, understood by and signed by patient/guardian
See 4 more

Exclusion Criteria

I do not have any active infections, except possibly Hepatitis B or C.
I have had an organ transplant.
Known HIV positivity
See 1 more

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 to prepare for T-cell infusion

1 week
3 visits (in-person)

T-cell Infusion

Participants receive 21.15.GPC3-CAR T cells infusion 48 to 72 hours after completing chemotherapy

1 day
1 visit (in-person)

Initial Follow-up

Participants are monitored for safety and effectiveness after T-cell infusion, including tumor measurements and blood tests

4 weeks
Multiple visits (in-person and virtual)

Long-term Follow-up

Participants are monitored for long-term safety and T-cell persistence, with blood draws and health assessments

15 years
Every 3 months for 1 year, every 6 months for 4 years, then annually

Treatment Details

Interventions

  • 21.15.GPC3-CAR T cells
Trial Overview The trial is testing a new type of T cell therapy called 21.15.GPC3-CAR T cells designed to target and kill tumor cells in adults with GPC3-positive solid tumors. These engineered T cells also carry genes that help them grow better and last longer in the body.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: 21.15.GPC3-CAR T cellsExperimental Treatment1 Intervention
GPC3-CAR and the IL15 plus IL21 will be administered to patients with GPC3-positive solid tumors.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials
1,044
Recruited
6,031,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials
114
Recruited
2,900+

Findings from Research

T cells engineered with GPC3-targeted chimeric antigen receptors (CAR) effectively kill GPC3-positive hepatocellular carcinoma (HCC) cells in vitro, demonstrating a strong correlation between their cytotoxic activity and the level of GPC3 expression in target cells.
In vivo studies showed that third-generation GPC3-targeted CAR T cells could eradicate HCC xenografts with high GPC3 expression and significantly prolong the survival of mice with established tumors, indicating their potential as a promising treatment for GPC3-positive HCC.
Development of T cells redirected to glypican-3 for the treatment of hepatocellular carcinoma.Gao, H., Li, K., Tu, H., 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.
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]
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.
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]

References

Development of T cells redirected to glypican-3 for the treatment of hepatocellular carcinoma. [2022]
Armored Inducible Expression of IL-12 Enhances Antitumor Activity of Glypican-3-Targeted Chimeric Antigen Receptor-Engineered T Cells in Hepatocellular Carcinoma. [2020]
Redirecting T Cells to Glypican-3 with 4-1BB Zeta Chimeric Antigen Receptors Results in Th1 Polarization and Potent Antitumor Activity. [2022]
[Construction and function of Glypican-3-targeted fourth-generation chimeric antigen receptor T cells (secreting IL-7 and CCL19)]. [2020]
Adoptive immunotherapy using T lymphocytes redirected to glypican-3 for the treatment of lung squamous cell carcinoma. [2020]
Toxicity and management in CAR T-cell therapy. [2023]
Development of T cells carrying two complementary chimeric antigen receptors against glypican-3 and asialoglycoprotein receptor 1 for the treatment of hepatocellular carcinoma. [2017]
The efficacy and safety of anti-CD19/CD20 chimeric antigen receptor- T cells immunotherapy in relapsed or refractory B-cell malignancies:a meta-analysis. [2018]
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