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. This study has a substudy component that will investigate the safety and tolerability of MAGE-A4c1032T cell therapy in combination with low dose radiation in up to 10 subjects.

Related Conditions:
  • Malignant Esophagogastric Neoplasm
  • Malignant Head and Neck Neoplasm
  • Malignant Ovarian Neoplasm
  • Melanoma
  • Myxoid Liposarcoma
  • Non-Small Cell Lung Carcinoma
  • Round Cell Liposarcoma
  • Synovial Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT03132922

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
  • Gastroesophageal Junction

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. This study has a substudy component that will investigate the safety and tolerability of MAGE-A4c1032T cell therapy in combination with low dose radiation in up to 10 subjects.

Trial Arms

NameTypeDescriptionInterventions
Autologous genetically modified MAGE-A4ᶜ¹º³²T cellsExperimental
    Radiation Sub-Study: Autologous genetically modified MAGE-A4c1Experimental

      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 indicated tumor types

          3. Subject is HLA-A*02 positive. (This determination will be made under screening
             protocol ADP-0000-001).

          4. Subject's tumor shows expression of the MAGE-A4 RNA or protein. (This determination
             will be made under screening protocol ADP-0000-001).

          5. Adequate organ function as indicated in the study protocol

          6. Subject has measurable disease according to RECIST v1.1 criteria prior to
             lymphodepletion

          7. Subject meets disease-specific requirements per protocol

        7. Subject has anticipated life expectancy > 6 months prior to leukapheresis and >3 months
        prior to lymphodepletion.

        Exclusion Criteria:

          1. Subject does not express appropriate HLA-A genotype

          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.

        Additional Exclusion Criteria for the Radiation Substudy:

          -  Subject does not meet eligibility criteria for the main study (ADP-0044-001).

          -  Subject does not have at least one target lesion amenable to radiation.

          -  Certain radiation therapy within 6 months of clinical trial are an exclusion.

          -  Metastatic disease impinging on the spinal cord or threatening spinal cord
             compression.
      Maximum Eligible Age:75 Years
      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
      • Radiation therapy

      Last Updated

      August 12, 2021