CAR T Cells for Liver Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Roswell Park Cancer Institute

Must be taking: Antivirals

Must not be taking: Glucocorticoids

Disqualifiers: Child-Pugh B/C cirrhosis, Active bleeding, Alcohol abuse, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to determine the safest and most effective dose of RPCAR01 CAR T cells for treating advanced liver cancer that overproduces the protein GPC3. CAR T cells are immune cells modified to better recognize and attack cancer cells. Suitable candidates for this trial include individuals with metastatic liver cancer who have undergone at least two recommended treatments and have confirmed tumor overexpression of GPC3. As a Phase 1 trial, this research aims to understand how the treatment works in people, providing participants the opportunity to be among the first to receive this innovative 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 it does mention a washout period (time without taking certain medications) of 2 weeks before apheresis. It's best to discuss your specific medications with the trial team.

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

Research has shown that GPC3-CAR T cell therapy, such as RPCAR01, is generally safe for liver cancer patients. In earlier studies, patients found the therapy well-tolerated. Most side effects were manageable, and some patients even showed signs of treatment effectiveness.

This treatment uses specially modified immune cells to target and attack cancer cells with a specific protein called GPC3. Testing has indicated that this method works without causing serious problems for most patients. While side effects can occur, they are usually mild and controllable.

As this is an early-phase trial, the main goal is to ensure the dose is safe and to determine the optimal dose. Overall, early results are promising for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the use of Anti-GPC3-CAR Autologous T Lymphocytes for liver cancer because it offers a novel approach by harnessing the body's immune cells to target cancer. Unlike traditional treatments like chemotherapy and surgery, this therapy involves engineering a patient's own T cells to specifically attack cells expressing the GPC3 protein, which is commonly found on liver cancer cells. This targeted mechanism could potentially reduce damage to healthy cells and improve treatment effectiveness. Additionally, the personalized nature of CAR T cell therapy represents a significant shift towards more tailored cancer treatments.

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

Research shows that a new treatment called CAR T cells, specifically the RPCAR01 CAR T cells in this trial, target a protein called GPC3 and may help treat liver cancer. In early studies, these CAR T cells found and destroyed liver cancer cells with high levels of GPC3, a protein mostly present on cancer cells, not healthy ones. This allows the treatment to specifically target cancer cells. Scientists have also enhanced these CAR T cells to block another protein, TGFB, which can weaken the immune system. This enhancement helps the CAR T cells fight cancer more effectively. Additionally, when these CAR T cells target both GPC3 and another protein called AFP, they showed even better results in fighting liver cancer in research models. Overall, these findings suggest that RPCAR01 CAR T cells could be a promising treatment for advanced liver cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Anuradha Krishnamurthy

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with advanced or metastatic hepatocellular carcinoma (HCC) that overexpresses GPC3, a protein rarely found in healthy tissue. Participants must have HCC that has spread and are willing to undergo leukapheresis to provide T cells for treatment.

Inclusion Criteria

I've had 2 standard treatments for liver cancer, including immunotherapy and a drug like lenvatinib.

I have been diagnosed with liver cancer, not mixed with bile duct cancer.

My cancer can be measured and has grown or changed since last treatment.

Exclusion Criteria

I am not pregnant or breastfeeding.

I have had recent bleeding that hasn't stopped.

My liver condition is severe (Child-Pugh B or C).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Leukapheresis

Patients undergo leukapheresis to collect T cells for modification

1 day

1 visit (in-person)

Lymphodepletion Chemotherapy

Patients receive cyclophosphamide and fludarabine to prepare for CAR T cell infusion

3 days

3 visits (in-person)

CAR T Cell Infusion

Patients receive RPCAR01 CAR T cells infusion

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Multiple visits at days 2, 3, 4, 5, 6, 7, 14, 28, months 2, 4, 6, 8, 10, 12

Long-term Follow-up

Participants are monitored for long-term outcomes and survival

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• Anti-GPC3-CAR Autologous T Lymphocytes

Trial Overview The trial tests RPCAR01 CAR T cells, which are the patient's own immune cells modified to target GPC3 on cancer cells. It includes lymphodepletion chemotherapy with cyclophosphamide and fludarabine before infusing the modified T cells back into the patient.

How Is the Trial Designed?

Group I: Treatment (RPCAR01 CAR T cells) Experimental Treatment 9 Interventions

Patients undergo leukapheresis within 28 days prior to RPCAR01 CAR T cell infusion. Patients then receive cyclophosphamide IV over 2 hours and fludarabine IV over 30 minutes on days -5, -4, and -3 and RPCAR01 CAR T cells IV over 15 minutes on day 1 in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA during screening and blood sample collection and CT or MRI throughout the trial. Patients may also optionally undergo tissue sample collection throughout the trial.

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06968195

NCT06968195 | Autologous CAR T Cells Targeting GPC3 ... This phase I trial studies the side effects and best dose of RPCAR01 chimeric antigen receptor (CAR) T cells and to see how well it works in treating ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12186358/

Advancing liver cancer treatment with dual-targeting CAR-T ... To enhance treatment outcomes for liver cancer, we further modified previously developed GPC3 CAR-T cells, which demonstrated robust anti-tumor ...

3. 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).

4. biomarkerres.biomedcentral.com biomarkerres.biomedcentral.com/articles/10.1186/s40364-021-00350-4/tables/5

Table 5 Ongoing studies investigating CAR-T for HCC Table 5 Ongoing studies investigating CAR-T for HCC ; Anti-GPC3 CAR-T for Treating GPC3-positive Advanced Hepatocellular Carcinoma (HCC). NCT03084380. 1/2 ; A ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1687197924001308

Chimeric antigen receptor-T cells targeting AFP-GPC3 ... AFP and GPC3 dual-targeted CAR-T cells showed better anti-tumor effects in HCC than AFP or GPC3 single-targeted CAR-T cells.

6. careacross.com careacross.com/clinical-trials/trial/NCT06641453

CAR-T Cell Therapy Targeting GPC3 in Patients with ... The results from these trials demonstrated that GPC3-CAR T cell therapy is generally safe, with manageable adverse effects, and some patients exhibited clinical ...