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ET140203 T Cells in Pediatric Subjects With Hepatoblastoma, HCN-NOS, or Hepatocellular Carcinoma (ARYA-2)

Primary Purpose

Hepatoblastoma, Hepatocellular Carcinoma (HCC), Liver Neoplasms

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

ET140203 T Cells

About this trial

This is an interventional treatment trial for Hepatoblastoma focused on measuring Relapsed/Refractory Hepatoblastoma (HB), Pediatric, Hepatocellular Neoplasm-Not Otherwise Specified (HCN-NOS), Hepatocellular Carcinoma (HCC), Liver Cancer, T-cell therapy, Metastatic Liver Cancer, Liver neoplasms, HEMNOS

Eligibility Criteria

1 Year - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Histologically confirmed HB, HCN-NOS, or HCC with serum AFP >200ng/ml at the time of screening and following the most recent line of therapy.
Disease reoccurrence after remission following initial standard-of-care (SOC) treatment (i.e. relapse) or failure of response to SOC treatment (i.e. refractory).
Age ≥ 1 year and ≤ 21 years.
Molecular Human Leukocyte Antigen (HLA) class I allele typing that confirms subject carries at least one HLA-A2 allele.
Life expectancy of > 4 months per Principal Investigator's opinion.
Lansky or Karnofsky Performance Scale ≥ 70.
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.
Child-Pugh score of B7 or better.
Adequate organ function.

Exclusion Criteria:

Received the following within two (2) weeks of leukapheresis and within two (2) weeks of conditioning chemotherapy: cytotoxic chemotherapy, radiation, systemic corticosteroids, other anti-cancer therapies (including immunotherapeutic agents), or any other immunosuppressive agents (Note: use of inhaled or topical steroids is not exclusionary).
Concurrently receiving other investigational agents, biological, chemical, or radiation therapies, while participating in the study.
Contraindication for receipt of conditioning chemotherapeutic agents including Fludarabine and Cyclophosphamide.
Active autoimmune disease requiring systemic immunosuppressive therapy.
Compromised circulation in the main portal vein, hepatic vein, or vena cava due to partial or complete obstruction which, in the opinion of the Principal Investigator, would make the subject unsuitable for the study.
History of organ transplant.
HB, HCN-NOS, or HCC involving greater than 50% of the liver (volumetric).

Sites / Locations

Dana-Farber/Boston Children's Cancer and Blood Disorders CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ET140203 T Cells

Arm Description

ET140203 T Cells

Outcomes

Primary Outcome Measures

Incidence rates of adverse events (AEs) after infusion of ET140203 T cells

Safety of ET140203 T cells as assessed by the number of adverse events (AEs) after infusion

Severity rates of adverse events (AEs) after infusion of ET140203 T cells

Safety of ET140203 T cells as assessed by the severity of adverse events (AEs) after infusion.

Incidence rates of dose limiting toxicities (DLTs) after infusion of ET140203 T cells

Tolerability of ET140203 T cells after infusions assessed by committee review of dose limiting toxicities (DLTs)

The recommended phase 2 dose (RP2D) regimen of ET140203 T cell therapy primarily based on DLT

The RP2D will be determined by the study Dose Escalation Committee (DEC) and primarily based on DLTs.

Secondary Outcome Measures

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 and assessed according to RECIST criteria.

Determine the pharmacokinetics of ET140203 T cells after infusion.

Assess the expansion and persistence of ET140203 T cells circulating in blood over time.

Full Information

NCT ID

NCT04634357

First Posted

November 4, 2020

Last Updated

December 15, 2022

Sponsor

Eureka Therapeutics Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04634357

Brief Title

ET140203 T Cells in Pediatric Subjects With Hepatoblastoma, HCN-NOS, or Hepatocellular Carcinoma

Acronym

ARYA-2

Official Title

An Open-Label, Dose Escalation, Phase I/II Clinical Trial of ET140203 T Cells in Pediatric Subjects With Relapsed/Refractory Hepatoblastoma (HB), Hepatocellular Neoplasm-Not Otherwise Specified (HCN-NOS), or Hepatocellular Carcinoma (HCC)

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Recruiting

Study Start Date

July 19, 2022 (Actual)

Primary Completion Date

January 31, 2026 (Anticipated)

Study Completion Date

January 31, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eureka Therapeutics Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

Open-label, dose escalation, multi-center, Phase I/II clinical trial to assess the safety/tolerability and determine the recommended Phase II Dose (RP2D) of ET140203 T-cells in pediatric subjects who are AFP-positive/HLA-A2-positive and have relapsed/refractory HB, HCN-NOS, or HCC.

Detailed Description

The trial starts with a dose escalation phase. A traditional dose escalation model (3+3) design will be used to determine the recommended phase II dose (RP2D). Subjects will then be treated at the RP2D in the expansion phase of the trial. Following treatment, tumor response assessments will be performed at Months 1, 3, 6, 9, 12, 18, and 24. At each tumor response assessment visit, imaging will be performed (triphasic CT Scan) and used for response evaluation. Serum AFP levels will also be measured at each tumor response assessment visit. The active assessment phase of the study will continue for 2 years. Subjects will be followed for 15 years post-treatment for assessment of treatment safety and overall survival.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatoblastoma, Hepatocellular Carcinoma (HCC), Liver Neoplasms, Metastatic Liver Cancer, Liver Cancer, HEMNOS

Keywords

Relapsed/Refractory Hepatoblastoma (HB), Pediatric, Hepatocellular Neoplasm-Not Otherwise Specified (HCN-NOS), Hepatocellular Carcinoma (HCC), Liver Cancer, T-cell therapy, Metastatic Liver Cancer, Liver neoplasms, HEMNOS

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

ET140203 T Cells

Arm Type

Experimental

Arm Description

ET140203 T Cells

Intervention Type

Drug

Intervention Name(s)

ET140203 T Cells

Intervention Description

Biological/Vaccine: ET140203 autologous T-cell product Autologous T cells transduced with lentivirus encoding an ET140203 expression construct

Primary Outcome Measure Information:

Title

Incidence rates of adverse events (AEs) after infusion of ET140203 T cells

Description

Safety of ET140203 T cells as assessed by the number of adverse events (AEs) after infusion

Time Frame

28 days

Title

Severity rates of adverse events (AEs) after infusion of ET140203 T cells

Description

Safety of ET140203 T cells as assessed by the severity of adverse events (AEs) after infusion.

Time Frame

28 days

Title

Incidence rates of dose limiting toxicities (DLTs) after infusion of ET140203 T cells

Description

Tolerability of ET140203 T cells after infusions assessed by committee review of dose limiting toxicities (DLTs)

Time Frame

28 days

Title

The recommended phase 2 dose (RP2D) regimen of ET140203 T cell therapy primarily based on DLT

Description

The RP2D will be determined by the study Dose Escalation Committee (DEC) and primarily based on DLTs.

Time Frame

Up to 2 years

Secondary Outcome Measure Information:

Title

Assess the efficacy of ET140203 T cells in pediatric subjects with relapsed/refractory HB, HCN-NOS, or HCC

Description

Response rate will be assessed by radiographic scans and assessed according to RECIST criteria.

Time Frame

Up to 2 years

Title

Determine the pharmacokinetics of ET140203 T cells after infusion.

Description

Assess the expansion and persistence of ET140203 T cells circulating in blood over time.

Time Frame

Up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Year

Maximum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically confirmed HB, HCN-NOS, or HCC with serum AFP >200ng/ml at the time of screening and following the most recent line of therapy. Disease reoccurrence after remission following initial standard-of-care (SOC) treatment (i.e. relapse) or failure of response to SOC treatment (i.e. refractory). Age ≥ 1 year and ≤ 21 years. Molecular Human Leukocyte Antigen (HLA) class I allele typing that confirms subject carries at least one HLA-A2 allele. Life expectancy of > 4 months per Principal Investigator's opinion. Lansky or Karnofsky Performance Scale ≥ 70. 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. Child-Pugh score of B7 or better. Adequate organ function. Exclusion Criteria: Received the following within two (2) weeks of leukapheresis and within two (2) weeks of conditioning chemotherapy: cytotoxic chemotherapy, radiation, systemic corticosteroids, other anti-cancer therapies (including immunotherapeutic agents), or any other immunosuppressive agents (Note: use of inhaled or topical steroids is not exclusionary). Concurrently receiving other investigational agents, biological, chemical, or radiation therapies, while participating in the study. Contraindication for receipt of conditioning chemotherapeutic agents including Fludarabine and Cyclophosphamide. Active autoimmune disease requiring systemic immunosuppressive therapy. Compromised circulation in the main portal vein, hepatic vein, or vena cava due to partial or complete obstruction which, in the opinion of the Principal Investigator, would make the subject unsuitable for the study. History of organ transplant. HB, HCN-NOS, or HCC involving greater than 50% of the liver (volumetric).

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Teresa Klask, BS

Phone

510-722-8719

Ext

412

Teresa.Klask@eurekainc.com

First Name & Middle Initial & Last Name or Official Title & Degree

Pei Wang, PhD

Phone

510-654-7045

Pei.Wang@eurekainc.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pei Wang, PhD

Organizational Affiliation

Eureka Therapeutics Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Dana-Farber/Boston Children's Cancer and Blood Disorders Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jami Brown

Phone

857-215-1688

Jami_Brown@DFCI.Harvard.edu

First Name & Middle Initial & Last Name & Degree

Allison O'Neill, MD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

ET140203 T Cells in Pediatric Subjects With Hepatoblastoma, HCN-NOS, or Hepatocellular Carcinoma

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