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

Sponsor
Eureka Therapeutics Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04634357
Collaborator
(none)
25
1
1
31.4
0.8

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: ET140203 T Cells
Phase 1/Phase 2

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
25 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Jul 19, 2022
Anticipated Primary Completion Date :
Feb 28, 2023
Anticipated Study Completion Date :
Feb 28, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: ET140203 T Cells

ET140203 T Cells

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

Outcome Measures

Primary Outcome Measures

  1. Incidence rates of adverse events (AEs) after infusion of ET140203 T cells [28 days]

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

  2. Severity rates of adverse events (AEs) after infusion of ET140203 T cells [28 days]

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

  3. Incidence rates of dose limiting toxicities (DLTs) after infusion of ET140203 T cells [28 days]

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

  4. The recommended phase 2 dose (RP2D) regimen of ET140203 T cell therapy primarily based on DLT [Up to 2 years]

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

Secondary Outcome Measures

  1. Assess the efficacy of ET140203 T cells in pediatric subjects with relapsed/refractory HB, HCN-NOS, or HCC [Up to 2 years]

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

  2. Determine the pharmacokinetics of ET140203 T cells after infusion. [Up to 2 years]

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

Eligibility Criteria

Criteria

Ages Eligible for Study:
1 Year to 21 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. 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.

  2. Disease reoccurrence after remission following initial standard-of-care (SOC) treatment (i.e. relapse) or failure of response to SOC treatment (i.e. refractory).

  3. Age ≥ 1 year and ≤ 21 years.

  4. Molecular Human Leukocyte Antigen (HLA) class I allele typing that confirms subject carries at least one HLA-A2 allele.

  5. Life expectancy of > 4 months per Principal Investigator's opinion.

  6. Lansky or Karnofsky Performance Scale ≥ 70.

  7. 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.

  8. Child-Pugh score of B7 or better.

  9. Adequate organ function.

Exclusion Criteria:
  1. 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).

  2. Concurrently receiving other investigational agents, biological, chemical, or radiation therapies, while participating in the study.

  3. Contraindication for receipt of conditioning chemotherapeutic agents including Fludarabine and Cyclophosphamide.

  4. Active autoimmune disease requiring systemic immunosuppressive therapy.

  5. 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.

  6. History of organ transplant.

  7. HB, HCN-NOS, or HCC involving greater than 50% of the liver (volumetric).

Contacts and Locations

Locations

Site City State Country Postal Code
1 Dana-Farber/Boston Children's Cancer and Blood Disorders Center Boston Massachusetts United States 02215

Sponsors and Collaborators

  • Eureka Therapeutics Inc.

Investigators

  • Study Director: Pei Wang, PhD, Eureka Therapeutics Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Eureka Therapeutics Inc.
ClinicalTrials.gov Identifier:
NCT04634357
Other Study ID Numbers:
  • ETUS20AFPAR123
First Posted:
Nov 18, 2020
Last Update Posted:
Aug 15, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Eureka Therapeutics Inc.
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 15, 2022