Clinical Trials /

MAGE-A4ᶜ¹º³²T for Multi-Tumor

NCT03132922

Description:

This study will investigate the safety and tolerability of MAGE-A4ᶜ¹º³²T cell therapy in subjects who have the appropriate HLA-A2 tissue marker and whose urinary bladder, melanoma, head and neck, ovarian, non-small cell lung, esophageal, gastric, synovial sarcoma, or myxoid/round call liposarcoma (MRCLS) tumor has the MAGE-A4 protein expressed. This study will take a subject's T cells and give them a T cell receptor protein that recognizes and attacks the tumors.

Related Conditions:
  • Adenosquamous Lung Carcinoma
  • Bladder Urothelial Carcinoma
  • Esophageal Adenocarcinoma
  • Esophageal Squamous Cell Carcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Infiltrating Renal Pelvis and Ureter Urothelial Carcinoma
  • Large Cell Lung Carcinoma
  • Melanoma
  • Myxoid Liposarcoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Renal Pelvis Urothelial Carcinoma
  • Squamous Cell Lung Carcinoma
  • Synovial Sarcoma
  • Ureter Urothelial Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: MAGE-A4ᶜ¹º³²T for Multi-Tumor
  • Official Title: Phase 1 Dose Escalation, Multi-tumor Study to Assess the Safety, Tolerability and Antitumor Activity of Genetically Engineered MAGE-A4ᶜ¹º³²T in HLA-A2+ Subjects With MAGE-A4 Positive Tumors

Clinical Trial IDs

  • ORG STUDY ID: ADP-0044-001
  • NCT ID: NCT03132922

Conditions

  • Urinary Bladder Cancer
  • Melanoma
  • Head and Neck Cancer
  • Ovarian Cancer
  • Non-Small Cell Lung Cancer
  • Esophageal Cancer
  • Gastric Cancer
  • Synovial Sarcoma
  • Myxoid Round Cell Liposarcoma

Purpose

This study will investigate the safety and tolerability of MAGE-A4ᶜ¹º³²T cell therapy in subjects who have the appropriate HLA-A2 tissue marker and whose urinary bladder, melanoma, head and neck, ovarian, non-small cell lung, esophageal, gastric, synovial sarcoma, or myxoid/round call liposarcoma (MRCLS) tumor has the MAGE-A4 protein expressed. This study will take a subject's T cells and give them a T cell receptor protein that recognizes and attacks the tumors.

Trial Arms

NameTypeDescriptionInterventions
Autologous genetically modified MAGE-A4ᶜ¹º³²T cellsExperimental

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Subject is ≥18 years of age at the time of signing the study informed consent.
    
              2. Subject has histologically confirmed diagnosis of any one of the following cancers:
                 urothelial cancer (transitional cell cancer of the bladder, ureter, urethra or renal
                 pelvis), melanoma, squamous cell carcinoma of the head and neck, ovarian cancer, NSCLC
                 (squamous, adenosquamous, adenocarcinoma or large cell), esophageal (squamous and
                 adenocarcinoma) or gastric cancer, synovial sarcoma or MRCLS.
    
              3. Subject is HLA-A*02 positive and subject's tumor shows expression of the MAGE-A4 RNA
                 or protein.
    
              4. Subject has measurable disease according to RECIST v1.1 criteria prior to
                 lymphodepletion
    
              5. Subject meets disease-specific requirements per protocol
    
              6. Subject has anticipated life expectancy > 6 months prior to leukapheresis and >3
                 months prior to lymphodepletion.
    
            Exclusion Criteria:
    
              1. Subject is HLA-A*02:05 positive in either allele; Subject has HLA-A*02:07 as the sole
                 HLA-A*02 allele (e.g., a subject with HLA alleles A*02:04 and A*02:07 is eligible); or
                 Subject has any A*02 null allele (designated with an "N", e.g., A*02:32N) as the sole
                 HLA-A*02 allele
    
              2. Subject is receiving excluded therapy/treatment per protocol
    
              3. Subject has symptomatic CNS metastases.
    
              4. Subject has any other active malignancy besides the tumor under study within 3 years
                 prior to Screening. Subject has uncontrolled intercurrent illness.
    
              5. Subject has active infection with HIV, HBV, HCV or HTLV
    
              6. Subject is pregnant or breastfeeding.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Number of subjects with adverse events (AE), including serious adverse events (SAEs).
    Time Frame:3.5 years
    Safety Issue:
    Description:Determine if treatment with autologous genetically modified T cells (MAGE-A4ᶜ¹º³²T) is safe and tolerable through laboratory assessments including chemistry, hematology and coagulation.

    Secondary Outcome Measures

    Measure:Proportion of subjects with a confirmed Complete Response (CR) and/or Partial Response (PR).
    Time Frame:3.5 years
    Safety Issue:
    Description:Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1
    Measure:Interval between the date of first T cell infusion dose and first documented evidence of CR or PR.
    Time Frame:3.5 years
    Safety Issue:
    Description:Evaluation of the efficacy of the treatment by assessment of time to first response.
    Measure:Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause.
    Time Frame:3.5 years
    Safety Issue:
    Description:Evaluation of the efficacy of the treatment by assessment of duration of response.
    Measure:Interval between the date of first documented evidence of stable disease (SD) until first documented disease progression or death due to any cause.
    Time Frame:3.5 years
    Safety Issue:
    Description:Evaluation of the efficacy of the treatment by assessment of duration of stable disease.
    Measure:Interval between the date of first T cell infusion and the earliest date of disease, progression or death due to any cause
    Time Frame:3.5 years
    Safety Issue:
    Description:Evaluation of the efficacy of the treatment by assessment of progression-free survival.
    Measure:Interval between the date of first T cell infusion and date of death due to any cause.
    Time Frame:3.5 years
    Safety Issue:
    Description:Evaluation of the efficacy of the treatment by assessment of overall survival.
    Measure:Number and % of subjects having any Long Term Follow Up Adverse Events (AEs)
    Time Frame:15 years post last treatment (infusion)
    Safety Issue:
    Description:New occurrence of any malignancy New occurrence or exacerbation of a pre-existing neurologic disorder New occurrence or exacerbation of a prior rheumatologic or other autoimmune disorder New occurrence of a hematologic disorder New occurrence of any opportunistic and/or serious infections New occurrence of any unanticipated illness and/or hospitalization deemed related to gene modified cell therapy

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Adaptimmune

    Trial Keywords

    • Cell Therapy
    • T Cell Therapy
    • SPEAR T Cell
    • MAGE-A4
    • Immuno-oncology
    • Metastatic
    • Urothelial Cancer
    • Previously Treated
    • T Cell Receptor
    • Squamous, adenosquamous, adenocarcinoma or large cell NSCLC
    • Squamous or adenocarcinoma esophageal cancer
    • Sarcoma
    • Melanoma
    • Bladder
    • Ovarian

    Last Updated