ET140203 T Cells for Pediatric Liver Cancer

(ARYA-2 Trial)

Recruiting at 2 trial locations

Overseen By Teresa Klask, MBA

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Eureka Therapeutics Inc.

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Heart failure, Uncontrolled infections, Active malignancy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ET140203 T Cells, an autologous T-cell immunotherapy, for children and young adults with liver cancer that has recurred or resisted standard treatments. The main goal is to determine the treatment's safety and optimal dosage. It targets individuals with AFP-positive liver tumors (a type of protein in the blood) and HLA-A2-positive genetic markers. Suitable candidates are those who have not succeeded with other treatments and whose liver cancer affects less than half of their liver. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that participants stop taking certain medications, such as cytotoxic chemotherapy, radiation, other anti-cancer therapies, immunosuppressive therapy, or systemic corticosteroids above a certain dose, at least two weeks before certain procedures. However, topical and inhaled corticosteroids and physiological replacement doses for adrenal insufficiency are allowed.

Is there any evidence suggesting that ET140203 T Cells are likely to be safe for humans?

Research has shown that ET140203 T cells have been generally safe in similar trials for liver cancer. In studies with both adults and children, these T-cell therapies (a treatment using specially altered immune cells) have demonstrated promising safety results, meaning most participants did not experience serious side effects. The FDA has granted ET140203 T cells a special status for treating a type of liver cancer in children, indicating confidence in its safety for this use. While more research continues, past findings suggest the treatment is well-tolerated, offering hope for those considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for pediatric liver cancer, which often involve surgery, chemotherapy, and radiation, ET140203 T Cells offer a more targeted approach. This treatment uses a patient's own T cells that are engineered to recognize and attack cancer cells, potentially leading to more precise and effective elimination of the cancer. Researchers are excited because this method harnesses the body's immune system, which may reduce the severe side effects typically associated with conventional cancer therapies. Moreover, this immunotherapy could improve outcomes for patients who have not responded well to existing treatments.

What evidence suggests that ET140203 T Cells might be an effective treatment for pediatric liver cancer?

Research has shown that ET140203 T Cells, the treatment under study in this trial, could be promising for treating certain types of liver cancer in children. These T cells are engineered to find and attack specific proteins in liver cancer cells. Early studies suggest that ET140203 T Cells might improve patient outcomes by targeting cancer cells without harming healthy ones. This treatment uses a special receptor to focus on cancer cells, potentially making it more effective at shrinking tumors. The FDA has recognized its potential by granting it orphan drug designation for hepatoblastoma, a rare liver cancer in children. While more research is needed, initial results are encouraging for those with relapsed or difficult-to-treat liver cancers. ^{1 3 4 6 7}

Who Is on the Research Team?

Pei Wang, PhD

Principal Investigator

Eureka Therapeutics Inc.

Are You a Good Fit for This Trial?

This trial is for pediatric patients aged 1-21 with relapsed/refractory liver cancers (HB, HCN-NOS, or HCC) who are AFP-positive/HLA-A2-positive. They should have a life expectancy over 4 months and good performance status. Patients must not have had recent cancer treatments or other investigational therapies and should not be on systemic immunosuppressants.

Inclusion Criteria

For enrollment to the dose-finding cohort, subjects must have at least one (1) lesion ≥ 5 mm in diameter or two (2) or more lesions ≥ 3 mm in diameter. For the dose-expansion cohort, subjects must have measurable disease by RECIST v1.1.

My disease came back after initial treatment or didn't respond to it.

My organs are working well.

Exclusion Criteria

I am on medication to suppress my immune system due to an autoimmune disease.

I cannot take certain chemotherapy drugs like Fludarabine and Cyclophosphamide.

I haven't had certain cancer treatments or steroids in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

A traditional dose escalation model (3+3) design will be used to determine the recommended phase II dose (RP2D)

Up to 2 years

Expansion

Subjects will be treated at the RP2D in the expansion phase of the trial

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, with tumor response assessments at Months 1, 3, 6, 9, 12, 18, and 24

2 years

7 visits (in-person) for tumor response assessments

Long-term Follow-up

Subjects will be followed for 15 years post-treatment for assessment of treatment safety and overall survival

15 years

What Are the Treatments Tested in This Trial?

Interventions

• ET140203 T Cells

Trial Overview The trial tests ET140203 T-cells in children with specific liver cancers to find the safest dose that works best (Phase I/II). It's an open-label study where all participants receive the treatment, starting at lower doses which increase gradually to determine the optimal dose.

How Is the Trial Designed?

Group I: ET140203 T Cells Experimental Treatment 1 Intervention

ET140203 Autologous T Cells

ET140203 T Cells is already approved in United States for the following indications:

Approved in United States as ET140203 for:

• Hepatoblastoma (HB)

Who Is Running the Clinical Trial?

Eureka Therapeutics Inc.

Lead Sponsor

Trials

12

Recruited

160+

Published Research Related to This Trial

A new T cell receptor (TCR) targeting the alpha-fetoprotein (AFP) peptide has been identified as a promising candidate for immunotherapy against hepatocellular carcinoma (HCC), showing effective anti-tumor activity while minimizing cross-reactivity with normal tissues.

The selected AFP TCR has undergone rigorous testing for safety and efficacy, leading to the initiation of an early phase clinical trial (NCT03971747) to evaluate its effectiveness in treating HCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selection of a Clinical Lead TCR Targeting Alpha-Fetoprotein-Positive Liver Cancer Based on a Balance of Risk and Benefit. Luo, X., Cui, H., Cai, L., et al.[2021]

In a Phase I clinical trial involving 15 patients with primary hepatocellular carcinoma (HCC), adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TIL) demonstrated low toxicity, with only mild flu-like symptoms reported after treatment.

After a median follow-up of 14 months, all patients were alive, and 80% showed no evidence of disease, suggesting that this immunotherapy could be an effective new treatment option for HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I clinical trial utilizing autologous tumor-infiltrating lymphocytes in patients with primary hepatocellular carcinoma. Jiang, SS., Tang, Y., Zhang, YJ., et al.[2018]

The study involved 83 patients with hepatocellular carcinoma (HCC) and 15 healthy donors, revealing that γδ T cells can be effectively expanded using zoledronate and IL-2, which may enhance their potential for immunotherapy.

Despite the amplification of γδ T cells, their tumor-killing capacity and the levels of immunosuppressive factors like regulatory T cells (Tregs) and IL-17A remained unchanged, suggesting that these cells could be safely used in HCC treatment without increasing immunosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

γδ T cell-mediated individualized immunotherapy for hepatocellular carcinoma considering clinicopathological characteristics and immunosuppressive factors. Tian, W., Ma, J., Shi, R., et al.[2020]

The study successfully developed bispecific CAR T cells (CoG133-CAR T cells) targeting both CD133 and glypican-3 (GPC3) antigens in hepatocellular carcinoma (HCC), demonstrating enhanced tumor-suppression efficacy in both in vitro and in vivo models.

Using a non-viral minicircle DNA (mcDNA) vector for gene delivery resulted in high transfection efficiency and safety, with no significant 'off-target' effects observed in major organs, indicating a promising approach for CAR T therapy in solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonviral mcDNA-mediated bispecific CAR T cells kill tumor cells in an experimental mouse model of hepatocellular carcinoma. Wang, H., Wang, X., Ye, X., et al.[2022]

Adoptive T-cell transfer has shown clear clinical benefits in treating viral infections and posttransplant lymphoproliferative disease in pediatric patients, particularly after allogeneic transplants.

Recent advances in T-cell therapies for childhood malignancies focus on enhancing T-cell functions through strategies like gene modification and improving the host environment, although challenges remain in developing these therapies for various cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell-based therapies for malignancy and infection in childhood. Ahmed, N., Heslop, HE., Mackall, CL.[2021]

The administration of autologous invariant natural killer T (iNKT) cells in 10 patients with advanced hepatocellular carcinoma was found to be safe and well-tolerated, with no severe adverse events reported, even at high doses (up to 1×10^10 cells).

Expanded iNKT cells showed a strong T-helper 1-like immune response, producing significant amounts of cytokines associated with antitumor activity, suggesting potential effectiveness in treating hepatocellular carcinoma, warranting further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive Transfer of Autologous Invariant Natural Killer T Cells as Immunotherapy for Advanced Hepatocellular Carcinoma: A Phase I Clinical Trial. Gao, Y., Guo, J., Bao, X., et al.[2021]

Adoptive T cell transfer, particularly using engineered T cells like CAR T cells, has shown significant promise in cancer treatment by enhancing the immune system's ability to target and eliminate tumor cells, with reduced off-target toxicity.

The FDA granted 'breakthrough therapy' designation to anti-CD19 CAR T cell therapy in 2014, highlighting its potential effectiveness, which has been supported by numerous preclinical and clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T Cell Therapy in Hematology. Ataca, P., Arslan, Ö.[2018]

Using electroporation to introduce mRNA encoding anti-HBV T-cell receptors (TCR) into T cells resulted in about 80% of CD8(+) T cells expressing functional HBV TCR, which is significantly higher than the 18% achieved with traditional retroviral methods.

Although the functionality of these TCR-electroporated T cells was transient, they effectively prevented tumor growth and suppressed established tumors in a model of hepatocellular carcinoma (HCC), indicating a promising and safer approach for cell therapy in HCC and potentially other HBV-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A practical approach to immunotherapy of hepatocellular carcinoma using T cells redirected against hepatitis B virus. Koh, S., Shimasaki, N., Suwanarusk, R., et al.[2022]

Adoptive transfer of T cells with engineered T cell receptors (TCRs) shows potential as a treatment for hepatocellular carcinoma (HCC), especially since current treatment options are limited.

The study explores the possibility of targeting hepatitis B viral antigens as specific markers for HCC, suggesting that HBV-specific TCR redirected T cells could effectively attack cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cell receptor-therapy in HBV-related hepatocellularcarcinoma. Bertoletti, A., Brunetto, M., Maini, MK., et al.[2022]

In a randomized clinical trial involving 101 patients with hepatocellular carcinoma, the infusion of activated and expanded autologous peripheral blood lymphocytes showed a lower recurrence rate of cancer (13 cases) compared to the control group (22 cases).

Minor adverse reactions were reported in 57% of the treated patients, indicating that while the treatment may have some side effects, it is generally well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prevention of cancer recurrence by infusion of activated autologous lymphocytes]. Sekine, T., Takayama, T., Konomi, Y., et al.[2017]

TCR gene transfer can effectively generate AFP-specific cytotoxic T lymphocytes (CTLs), which are crucial for targeting hepatocellular carcinoma (HCC), as demonstrated by increased specific cytotoxicity and IFN-γ secretion in engineered T cells.

The study showed that transgenic CTLs had a significantly higher ability to recognize and kill AFP+ HCC cells both in vitro and in vivo compared to traditional methods using peptide-pulsed dendritic cells, indicating a more effective approach for immunotherapy against HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineered cytotoxic T lymphocytes with AFP-specific TCR gene for adoptive immunotherapy in hepatocellular carcinoma. Sun, L., Guo, H., Jiang, R., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04634357

NCT04634357 | ET140203 T Cells in Pediatric Subjects ... Assess the efficacy of ET140203 T cells in pediatric subjects with relapsed/refractory HB, HCN-NOS, or HCC, Response rate will be assessed by radiographic scans ...

2. cancernetwork.com cancernetwork.com/view/fda-grants-orphan-drug-designation-to-et140203-t-cells-for-hepatoblastoma

FDA Grants Orphan Drug Designation to ET140203 T Cells ... Primary outcome measures include the incidence of adverse effects (AEs) following ET140203 T-cell infusion, severity rates of AEs after infusion ...

3. cgtlive.com cgtlive.com/view/t-cell-therapy-recognized-pediatric-hepatoblastoma

T-Cell Therapy Recognized for Treating Pediatric ... ET140203 is developed using Eureka's proprietary ARTEMIS cell receptor to express a T-cell receptor (TCR) mimic antibody that targets an alpha ...

4. withpower.com withpower.com/trial/phase-2-carcinoma-8-2021-266c0

ET140203 T Cells for Pediatric Liver Cancer (ARYA-2 Trial) The ARYA-2 medical study, being run by Eureka Therapeutics Inc., is evaluating whether ET140203 T Cells will have tolerable side effects & efficacy for ...

5. onclive.com onclive.com/view/fda-grants-orphan-drug-designation-to-et140203-for-hepatoblastoma

FDA Grants Orphan Drug Designation to ET140203 for ... The FDA has granted an orphan drug designation (ODD) to ET140203 for the treatment of patients with hepatoblastoma, a rare childhood tumor in the liver.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04502082

NCT04502082 | Study of ET140203 T Cells in Adults With ... The purpose of this study is to investigate an autologous T-cell therapy for advanced hepatocellular carcinoma (HCC).

7. clinicaltrialsarena.com clinicaltrialsarena.com/news/eureka-artemis-t-cell-paediatric-liver-cancer/

Eureka starts ARTEMIS T-cell therapy trial for paediatric ... The multi-centre, open-label, dose-escalation clinical study will evaluate the preliminary efficacy and safety/tolerability of ET140203 T-cells ...