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Spearhead 1 Study in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma

NCT04044768

Description:

This is a study of genetically engineered ADP-A2M4 in HLA-A*02 subjects with metastatic or inoperable (advanced) Synovial Sarcoma or MRCLS who have received prior chemotherapy and whose tumor expresses the MAGE-A4 tumor antigen.

Related Conditions:
  • Myxoid Liposarcoma
  • Synovial Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Spearhead 1 Study in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma
  • Official Title: A Phase 2 Single Arm Open-Label Clinical Trial of ADP-A2M4 SPEAR™ T Cells in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma

Clinical Trial IDs

  • ORG STUDY ID: ADP 0044-002
  • NCT ID: NCT04044768

Conditions

  • Synovial Sarcoma
  • Myxoid Liposarcoma

Purpose

This is a study of genetically engineered ADP-A2M4 in HLA-A*02 subjects with metastatic or inoperable (advanced) Synovial Sarcoma or MRCLS who have received prior chemotherapy and whose tumor expresses the MAGE-A4 tumor antigen.

Trial Arms

NameTypeDescriptionInterventions
Autologous genetically modified ADP-A2M4Experimental

    Eligibility Criteria

            Key Inclusion Criteria
    
              -  Age ≥16 and <75 years
    
              -  Diagnosis of advanced synovial sarcoma or myxoid liposarcoma / myxoid round cell
                 liposarcoma confirmed by cytogenetics.
    
              -  Previously received either an anthracycline or ifosfamide containing regimen.
    
              -  Measurable disease according to RECIST v1.1.
    
              -  HLA-A*02 positive
    
              -  Tumor shows MAGE-A4 expression confirmed by central laboratory.
    
              -  ECOG Performance Status of 0 or1.
    
              -  Left ventricular ejection fraction (LVEF) ≥40%.
    
            Note: other protocol defined Inclusion criteria may apply
    
            Key Exclusion Criteria:
    
              -  HLA-A*02:05 in either allele; HLA-A*02:07 or any A*02 null allele as the sole HLA-A*02
                 allele
    
              -  History of allergic reactions attributed to compounds of similar chemical or biologic
                 composition to fludarabine, cyclophosphamide or other agents used in the study.
    
              -  History of autoimmune or immune mediated disease
    
              -  Leptomeningeal disease, carcinomatous meningitis or symptomatic CNS metastases.
    
              -  Other prior malignancy that is not considered by the Investigator to be in complete
                 remission
    
              -  Clinically significant cardiovascular disease
    
              -  Uncontrolled intercurrent illness
    
              -  Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C
                 virus, or human T cell leukemia virus
    
              -  Pregnant or breastfeeding
    
            Note: other protocol defined Exclusion criteria may apply.
          
    Maximum Eligible Age:75 Years
    Minimum Eligible Age:16 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Efficacy: Overall Response Rate (ORR)
    Time Frame:2.5 years
    Safety Issue:
    Description:ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1

    Secondary Outcome Measures

    Measure:Number of subjects with treatment -related adverse events (AEs), including serious adverse events (SAEs) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
    Time Frame:2.5 years
    Safety Issue:
    Description:Determine if treatment with ADP-A2M4 is safe and tolerable through assessment of adverse events (AEs) including Serious Adverse Events (SAEs
    Measure:Evaluate safety of ADP-A2M4 through measurement of Replication -competent Retrovirus in genetically engineered T-cells
    Time Frame:2.5 years
    Safety Issue:
    Description:Evaluation of RCL using PCR -based assay in peripheral blood.
    Measure:Measurement of T-cell clonality and insertional oncogenesis in peripheral blood mononuclear cells (PBMCs).
    Time Frame:2.5 years
    Safety Issue:
    Description:Measurement of T-cell clonality and insertional oncogenesis in peripheral blood mononuclear cells (PBMCs )
    Measure:Efficacy: Best overall response (BOR)
    Time Frame:2.5 years
    Safety Issue:
    Description:BOR is per RECIST V1.1.
    Measure:Time to response (TTR)
    Time Frame:2.5 years
    Safety Issue:
    Description:For patients who are observed to respond to ADP-A2M4, the time taken from date of infusion to achieve a partial response or complete response (TTR) is assessed.
    Measure:Duration of Response (DoR)
    Time Frame:2.5 years
    Safety Issue:
    Description:For patients who are observed to respond to ADP-A2M4, the DoR is the date of initial response (including confirmation) from date of infusion up until disease progression per RECIST v 1.1 or death.
    Measure:Progression Free Survival (PFS)
    Time Frame:2.5 years
    Safety Issue:
    Description:PFS is assessed from date of infusion of ADP-A2M4 up until the date of disease progression per RECIST v1.1 or death.
    Measure:Overall Survival (OS)
    Time Frame:15 years
    Safety Issue:
    Description:OS is assessed from date of infusion of ADP-A2M4 up until the date of patient death
    Measure:Quantitation of genetically engineered T-cells in PBMCs
    Time Frame:2.5 years
    Safety Issue:
    Description:Quantitation of genetically engineered T-cells in PBMCs by qPCR
    Measure:Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs
    Time Frame:2.5 years
    Safety Issue:
    Description:Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs by flow cytometry
    Measure:Quantitation of genetically engineered T-cells in PBMCs
    Time Frame:2.5 years
    Safety Issue:
    Description:Quantitation of genetically engineered T-cells in PBMCs by flow cytometry
    Measure:Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs
    Time Frame:2.5 years
    Safety Issue:
    Description:Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs by qPCR
    Measure:Invitro diagnostic (IVD) assay for screening
    Time Frame:2.5 years
    Safety Issue:
    Description:Development and validation of the MAGE-A4 antigen expression companion diagnostic assay

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Adaptimmune

    Trial Keywords

    • Cell Therapy
    • T Cell Therapy
    • SPEAR T Cell

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