CAR T Cells for Liver Cancer

(INTERCEPT Trial)

Overseen By Gentry King, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Seattle Children's Hospital

Must not be taking: Systemic steroids

Disqualifiers: Organ transplant, HIV, Active infection, others

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

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SC-CAR.GPC3xIL15.21 CAR T cells to determine its safety and effectiveness for individuals with liver cancer unresponsive to other treatments. The treatment uses specially modified cells from the patient's own blood to target their cancer. Individuals with liver cancer expressing GPC3, who have not found success with other treatments, might be suitable candidates. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking systemic steroid treatment at least 24 hours before the CAR T cell infusion. For other medications, the protocol does not specify, so it's best to discuss with the trial team.

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

Research has shown that SC-CAR.GPC3xIL15.21 CAR T cells yield promising results in lab studies. These studies found that these specially modified T cells, which include components like IL15 and IL21, effectively kill cancer cells. This suggests they might also target cancer cells in people.

However, this treatment is currently in Phase 1 of clinical trials. This phase primarily assesses the treatment's safety and how well people tolerate it. As an early-stage trial, there is limited information from human testing. Phase 1 trials aim to determine safety and identify any side effects. Researchers closely monitor participants to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for liver cancer, which often include surgery, chemotherapy, and targeted therapies, the SC-CAR.GPC3xIL15.21 CAR T cell therapy uses a groundbreaking approach. This treatment involves engineering a patient's own T cells to specifically target and destroy cancer cells expressing the GPC3 protein, which is commonly found in liver cancer. Additionally, the inclusion of IL-15 in the treatment helps to enhance the survival and proliferation of these modified T cells, potentially leading to a more sustained immune response against the cancer. Researchers are excited about this therapy because it offers a targeted attack on cancer cells with the added benefit of potentially longer-lasting effects compared to traditional treatments.

What evidence suggests that this treatment might be an effective treatment for liver cancer?

Research has shown that a new treatment, SC-CAR.GPC3xIL15.21 CAR T cells, may help fight liver cancer. Participants in this trial will receive this experimental treatment through a single infusion of autologous SC-CAR.GPC3xIL15.21 T cells. These specialized cells are designed to locate and attack glypican-3 (GPC3), a protein found on some cancer cells. Lab studies demonstrated that these engineered T cells, which include IL15 and IL21, kill cancer cells more effectively and multiply better, enhancing their ability to attack cancer aggressively. While these results are promising, they are based on early data, and further research is needed to confirm their effectiveness in people. ^{1 2 3 4 6}

Who Is on the Research Team?

Colleen Annesley

Principal Investigator

Seattle Children's Hospital

Corinne Summers

Principal Investigator

Seattle Children's Hospital

Are You a Good Fit for This Trial?

Adults with certain solid tumors that haven't responded to other treatments can join this trial. The tumors must have a marker called GPC3. Participants will provide a blood sample for creating personalized CAR T cells designed to target their cancer.

Inclusion Criteria

Life expectancy of >16 weeks

Informed consent explained to, understood by and signed by participant or participant's legally authorized representative

Adequate laboratory values

Exclusion Criteria

Pregnancy or lactation

History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment for patients who have received prior therapy with murine antibodies.

I do not have any active infections, except possibly for 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)

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy for 3 days using cyclophosphamide and fludarabine to prepare for CAR T cell infusion

1 week

3 visits (in-person)

CAR T Cell Infusion

Participants receive a single infusion of SC-CAR.GPC3xIL15.21 T cells and are monitored closely for side effects and response

4 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with visits becoming less frequent over time

15 years

Regular visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• SC-CAR.GPC3xIL15.21 CAR T cells

Trial Overview The study is testing bioengineered T cells, specifically SC-CAR.GPC3xIL15.21 CAR T cells, in adults with solid tumors expressing GPC3. These special immune cells are modified to fight cancer and include an 'off switch' gene for safety.

How Is the Trial Designed?

Group I: SC-CAR.GPC3xIL15.21 T cells Experimental Treatment 1 Intervention

Autologous SC-CAR.GPC3xIL15.21 T cell product infused as a single infusion.

Who Is Running the Clinical Trial?

Seattle Children's Hospital

Lead Sponsor

Trials

319

Recruited

5,232,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07224568

Cytokine Armored GPC3 Specific Chimeric Antigen ... When this was done in the laboratory, the investigators found that this mixture of GPC3-CAR, IL15, and IL21 in T cells killed tumor cells better when compared ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31953246/

Glypican-3-Specific CAR T Cells Coexpressing IL15 and IL21 ... Glypican-3-Specific CAR T Cells Coexpressing IL15 and IL21 Have Superior Expansion and Antitumor Activity against Hepatocellular Carcinoma.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07148050

Study Details | NCT07148050 | Immunotherapy for Solid ... When we did this in the laboratory, we found that this mixture of GPC3-CAR, IL15, and IL21 in T cells killed tumor cells better when compared ...

4. link.springer.com link.springer.com/article/10.1007/s10238-024-01473-2

IL-21- and CXCL9-engineered GPC3-specific CAR-T cells ... Several studies revealed that IL-21 can enhance the expansion of CAR-T cells, prevent CD19 CAR-T cells from differentiating into late memory ...

5. withpower.com withpower.com/trial/phase-1-liposarcoma-3-2026-11f64

CAR T Cells for Liver Cancer · Info for Participants Trial Overview The study is testing bioengineered T cells, specifically SC-CAR.GPC3xIL15.21 CAR T cells, in adults with solid tumors expressing GPC3. These ...

6. ichgcp.net ichgcp.net/amp/clinical-trials-registry/NCT07224568

SC-CAR.GPC3xIL15.21 CAR T cells in Hepatocellular Carcinoma ... When this was done in the laboratory, the investigators found that this mixture of GPC3-CAR, IL15, and IL21 in T cells killed tumor cells better when compared ...