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Genetically Engineered Cells (MAGE-A1-specific T Cell Receptor-transduced Autologous T-cells) and Atezolizumab for the Treatment of Metastatic Triple Negative Breast Cancer, Urothelial Cancer, or Non-small Cell Lung Cancer

NCT04639245

Description:

This phase I/II trial investigates the side effects of genetically engineered cells called FH-MagIC TCR-T cells and how well they work with atezolizumab in treating patients with triple negative breast cancer, urothelial cancer, or non-small cell lung cancer that has spread to other places in the body (metastatic). T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize MAGE-A1, a protein on the surface of tumor cells. These MAGE-A1-specific T cells may help the body's immune system identify and kill MAGE-A1 tumor cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving FH-MagIC TCR-T cells with atezolizumab may help treat patients with triple negative breast cancer, urothelial cancer, or non-small cell lung cancer.

Related Conditions:
  • Breast Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Genetically Engineered Cells (MAGE-A1-specific T Cell Receptor-transduced Autologous T-cells) and Atezolizumab for the Treatment of Metastatic Triple Negative Breast Cancer, Urothelial Cancer, or Non-small Cell Lung Cancer
  • Official Title: ATTAMAGE-A1.: Phase I/II Study of Autologous CD8+ and CD4+ Transgenic T Cells Expressing High Affinity MAGE-A1-Specific T-Cell Receptor (TCR) Combined With Atezolizumab in Patients With Metastatic MAGE-A1 Expressing Cancer

Clinical Trial IDs

  • ORG STUDY ID: RG1007463
  • SECONDARY ID: NCI-2020-06602
  • SECONDARY ID: 10420
  • NCT ID: NCT04639245

Conditions

  • Anatomic Stage IV Breast Cancer AJCC v8
  • Metastatic Lung Non-Small Cell Carcinoma
  • Metastatic Malignant Solid Neoplasm
  • Metastatic Triple-Negative Breast Carcinoma
  • Metastatic Urothelial Carcinoma
  • Prognostic Stage IV Breast Cancer AJCC v8
  • Stage IV Lung Cancer AJCC v8
  • Stage IVA Lung Cancer AJCC v8
  • Stage IVB Lung Cancer AJCC v8

Interventions

DrugSynonymsArms
AtezolizumabMPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, TecentriqTreatment (FH-MagIC TCR-T cells, atezolizumab)
Cyclophosphamide(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719Treatment (FH-MagIC TCR-T cells, atezolizumab)
FludarabineFluradosaTreatment (FH-MagIC TCR-T cells, atezolizumab)
MAGE-A1-specific T Cell Receptor-transduced Autologous T-cellsMAGE-A1-specific T Cell Receptor-transduced Autologous CD8+ and CD4+ T-cells, MAGE-A1-specific TCR-transduced Autologous T-cellsTreatment (FH-MagIC TCR-T cells, atezolizumab)
PD1 InhibitorPD-1 Inhibitor, PD-1-targeting Agent, Programmed Cell Death Protein 1 Inhibitor, Protein PD-1 InhibitorTreatment (FH-MagIC TCR-T cells, atezolizumab)

Purpose

This phase I/II trial investigates the side effects of genetically engineered cells called FH-MagIC TCR-T cells and how well they work with atezolizumab in treating patients with triple negative breast cancer, urothelial cancer, or non-small cell lung cancer that has spread to other places in the body (metastatic). T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize MAGE-A1, a protein on the surface of tumor cells. These MAGE-A1-specific T cells may help the body's immune system identify and kill MAGE-A1 tumor cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving FH-MagIC TCR-T cells with atezolizumab may help treat patients with triple negative breast cancer, urothelial cancer, or non-small cell lung cancer.

Detailed Description

      OUTLINE:

      This is a phase I, dose escalation study of FH-MagIC TCR-T cells followed by a phase II
      study.

      LYMPHODEPLETION: Patients receive cyclophosphamide intravenously (IV) and fludarabine IV on
      days -4, -3, and -2 before each T-cell infusion.

      T-CELL INFUSION: Patients receive FH-MagIC TCR-T cells IV over 15-20 minutes. Six to twelve
      weeks after first T-cell infusion, patients with progressive disease and non-persisting
      transgenic TCR T cells may receive a second T-cell infusion.

      In the Phase 2 portion of the study, atezolizumab will be administered as standard of care
      beginning 24-72 hours after T-cell infusion. Atezolizumab will be given IV every 3 weeks for
      at least 1 year in the absence of disease progression or unacceptable toxicity. If an
      alternative PD1 inhibitor is instead available for a patient, it may be substituted instead.

      After completion of study treatment, patients are followed up annually for 15 years after
      final infusion of FH-MagIC TCR-T.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (FH-MagIC TCR-T cells, atezolizumab)ExperimentalLYMPHODEPLETION: Patients receive cyclophosphamide IV and fludarabine IV on days -4, -3, and -2 before each T-cell infusion. T-CELL INFUSION: Patients receive FH-MagIC TCR-T cells IV over 15-20 minutes. Six to twelve weeks after first T-cell infusion, patients with progressive disease and non-persisting transgenic TCR T cells may receive a second T-cell infusion. In the Phase II portion of the study, patients will receive atezolizumab IV every 3 weeks beginning 24-72 hours after T cell infusion. Atezolizumab will be given for at least 1 year in the absence of disease progression or unacceptable toxicity. If an alternative PD1 inhibitor is instead available for a patient, it may be substituted instead.
  • Atezolizumab
  • Cyclophosphamide
  • Fludarabine
  • MAGE-A1-specific T Cell Receptor-transduced Autologous T-cells
  • PD1 Inhibitor

Eligibility Criteria

        Inclusion Criteria:

          -  Tissue confirmation of triple negative breast cancer (TNBC), urothelial carcinoma or
             non-small cell lung cancer (NSCLC) and expression of MAGEA1: Participants must have
             metastatic disease. Confirmation of diagnosis must be or have been performed by
             internal pathology review of archival, initial or subsequent biopsy or other
             pathologic material at Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer
             Care Alliance (SCCA)/University of Washington Medical Center (UWMC). Patients with
             TNBC must meet the American Society of Clinical Oncology - College of American
             Pathologists (ASCO-CAP) definition of negative estrogen, progesterone and HER2
             receptor expression. Baseline tissue will be stained to confirm MAGE-A1 expression

          -  Measurable disease by RECIST 1.1 criteria: Participants must have measurable disease,
             defined as at least one target lesion that can be measured in at least one dimension
             (longest diameter to be recorded) as >= 10 mm, unless lymph node in which case short
             axis must be >= 15 mm. Baseline imaging (for example diagnostic computed tomography
             [CT] chest/abdomen/pelvis and imaging of the affected extremity as appropriate), brain
             imaging (magnetic resonance imaging [MRI] or CT scan) must be obtained within 45 days
             of prior to start of first planned FH-MAGEA1-A2TCR infusion. MRI can be substituted
             for CT in patients unable to have CT contrast

          -  Previous treatment with standard of care (SOC) Food and Drug Administration
             (FDA)-approved therapies. Patients with NSCLC who have actionable somatic mutations or
             alterations in EGFR, ROS1 and ALK with FDA-approved drug therapy options will be
             eligible for study only after treatment with targeted therapies for those mutations
             have been offered or received. Patients with urothelial carcinoma who are candidates
             for enfortumab vedotin (enfortumab vedotin-ejfv) will be eligible for study after
             prior treatment with enfortumab vedotin-ejfv has been offered or received

          -  Previous treatment with PD-1 axis inhibitor: Patients in Phase I/2 must have been
             offered or been previously treated with at least one dose of a PD-L1 axis inhibitor
             (e.g. PD-1 or PD-L1 inhibiting monoclonal antibody such as pembrolizumab, nivolumab,
             avelumab, atezolizumab, durvalumab). If received, they must have either developed
             progression or still have detectable disease and not have developed Common Terminology
             Criteria for Adverse Events (CTCAE) grade 3 or higher toxicity while on treatment.
             Patients may have received 1 or more prior systemic regimens for metastatic TNBC or
             NSCLC. There is no upper limit on prior regimens. Patients may have received prior
             anti-PD-1/anti-PD-L1 in the neoadjuvant or adjuvant setting

          -  HLA type HLA-A*02:01: Participants must be HLA-A*02:01 in order for infused transgenic
             T cells in order to insure recognition of antigen-MHC complexes. HLA typing should be
             determined though a molecular approach in a clinical laboratory licensed for HLA
             typing

          -  Life expectancy must be anticipated to be > 3 months at trial entry

          -  Capable of understanding and providing a written informed consent

          -  If fertile, willingness to comply with reproductive requirements

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

          -  Tumor tissue amenable to safe biopsy and subject willing to undergo serial tumor
             biopsies: Should there be no tumor tissue that is accessible for biopsy, patients will
             still be considered for participation, at discretion of the sponsor and in
             consultation with the investigator. Similarly, should an investigator determine that a
             biopsy cannot be performed safely for clinical reasons biopsies may be cancelled or
             retimed after confirming plan with the sponsor

          -  Participants must be at least three weeks from last systemic treatment: At least 3
             weeks must have passed since any: immunotherapy (for example, T-cell infusions,
             immunomodulatory agents, interleukins, vaccines), small molecule or chemotherapy
             cancer treatment, other investigational agents. There is no washout period for
             radiation, so long as radiated lesion is not the lesion being evaluated for RECIST
             measurements on the protocol. Bisphosphonates are permitted but the concurrent
             treatment with RANK ligand inhibitors (i.e., denosumab) is not permitted within 8
             weeks of treatment

          -  Serum creatine < 2.5 mg/dL or estimated glomerular filtration rate (eGFR) > 30 mL/min

          -  Total bilirubin (tBili) < 3.0 mg/dL. Patients with suspected Gilbert syndrome may be
             included if Tbili > 3 but no other evidence of hepatic dysfunction

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x upper limit
             of normal (ULN)

          -  =< grade 1 dyspnea and oxygen saturation (SaO2) >= 92% on ambient air. If pulmonary
             function tests (PFTs) are performed based on the clinical judgement of the treating
             physician, patients with forced expiratory volume in 1 second (FEVI) >= 50% of
             predicted and carbon monoxide diffusing capability test (DLCO) (corrected) of >= 40%
             of predicted will be eligible

          -  Patients 60 years of age or older are required to have left ventricular ejection
             fraction (LVEF) evaluation performed within 60 days prior to enrollment. LVEF may be
             established with echocardiogram or multigated acquisition scan (MUGA) scan, and left
             ejection fraction must be >= 35%. Cardiac evaluation for other patients is at the
             discretion of the treating physician

          -  Absolute neutrophil count (ANC) > 500 cells/ mm^3

        Exclusion Criteria:

          -  Expression of HLA B*4901: participants will be excluded due to the risk of
             alloreactivity

          -  Participants of childbearing potential must have a negative serum pregnancy test
             within 14 days prior to enrollment. Childbearing potential is defined as women who
             have not been surgically sterilized and who are not postmenopausal (free of menses for
             at least 1 year)

          -  Patients with active autoimmune disease requiring immunosuppressive therapy are
             excluded. Case-by-case exemptions are possible with approval by principal investigator
             (PI)

          -  Prior solid organ transplant or allogenic hematopoietic stem cell transplant: Kidney
             transplant patients will be considered on a case-by-case basis requiring discussion
             with PI. If kidney transplant, patient must have dialysis access, dialysis plan,
             supportive nephrologist, willingness to stop transplant immunosuppression, and express
             understanding that rejection is possible outcome. Dialysis or costs related to
             transplant kidney will not be supported by the study. Participants having had any
             other solid organ transplants will be excluded, as will those with any history of
             allogeneic stem cell transplant

          -  Corticosteroid therapy at a dose equivalent of > 0.5 mg/kg of prednisone-equivalent
             per day

          -  Concurrent use of other investigational anti-cancer agents

          -  Chronic lymphocytic leukemia (CLL) or other active hematologic malignancy

          -  Active uncontrolled infection: Human immunodeficiency virus (HIV) positive
             participants on highly active anti-retroviral therapy (HAART) with a CD4 count > 500
             cells/mm^3 are considered controlled, as are individuals with a history of hepatitis C
             who have successfully completed antiviral therapy with an undetectable viral load, and
             those with hepatitis B who have, per standard practice, hepatitis well-controlled on
             medication (e.g., AST and ALT < 5 x ULN)

          -  Participants may not have uncontrolled or concurrent illness including, but not
             limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Participants with small asymptomatic brain metastases (< 1 cm) or those with brain
             metastases previously treated with surgery or radiotherapy will be considered for
             inclusion at discretion of principal investigator, so long as other eligibility
             criteria are met.

          -  For patients in phase 1/2, grade 3 or higher immune-mediated toxicity to any prior
             PD-L1 axis blocking agent

          -  Active treatment for prior immune related adverse event to any immunotherapy:
             Participants receiving ongoing treatment for prior serious immune related adverse
             events are excluded, with exception of hormone supplementation or corticosteroid
             therapy at equivalent of up to 0.5 mg/kg prednisone per day, unless otherwise approved
             by PI

          -  Study participants must not have significant active underlying neurologic disease,
             unless approved by PI. Neuropathy related to diabetes or prior chemotherapy is
             acceptable

          -  Other medical, social, or psychiatric factor that interferes with medical
             appropriateness and/or ability to comply with study, as determined by the PI
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of treatment-related unexpected grade 3 or higher adverse events
Time Frame:Up to 15 years
Safety Issue:
Description:Lesions will be separately tracked but response determined in totality. As indicated, patient must have at least one trackable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Response will be a defined as best overall response by RECIST 1.1 of complete or partial response.

Secondary Outcome Measures

Measure:Peripheral blood concentration of infused transgenic T cells over time
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Concentration of transgenic T cells in tumor tissue
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Progression-free survival
Time Frame:From time of first T-cell infusion, assessed up to 15 years
Safety Issue:
Description:Will be estimated using the method of Kaplan and Meier.
Measure:Overall survival
Time Frame:From time of first T-cell infusion, assessed up to 15 years
Safety Issue:
Description:Will be estimated using the method of Kaplan and Meier.
Measure:Objective response rates
Time Frame:Up to 15 years
Safety Issue:
Description:Evaluated by immune-related RECIST criteria.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Fred Hutchinson Cancer Research Center

Last Updated

December 3, 2020