Clinical Trials /

TCR-engineered T Cells in Solid Tumors (ACTengine IMA201-101)

NCT03247309

Description:

The study purpose is to establish the safety and tolerability of IMA201 in patients with solid tumors that express melanoma-associated antigen 4 or 8 (MAGEA4/8.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: TCR-engineered T Cells in Solid Tumors With Emphasis on NSCLC and HNSCC (ACTengine)
  • Official Title: Phase 1 Study Evaluating Genetically Modified Autologous T Cells Expressing a T-cell Receptor Recognizing a Cancer/Germline Antigen in Patients Having Solid Tumors Including But Not Limited to Non-small Cell Lung Cancer or Head and Neck Squamous Cell Carcinoma (ACTengineIMA201-101)

Clinical Trial IDs

  • ORG STUDY ID: IMA201-101
  • NCT ID: NCT03247309

Conditions

  • Solid Tumor
  • Cancer
  • Head and Neck Squamous Cell Carcinoma
  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
IMA201 ProductIMA201 Product

Purpose

The study purpose is to establish the safety and tolerability of IMA201 in patients with solid tumors that express melanoma-associated antigen 4 or 8 (MAGEA4/8.

Detailed Description

      SCREENING: Patient eligibility will be determined by HLA (human leukocyte antigen) screening
      and the main biomarkers screening. If the patient is eligible, white blood cells will be
      taken during leukapheresis for the manufacture of the IMA201 product.

      MANUFACTURING: IMA201 product will be made from the patient's white blood cells.

      TREATMENT: Lymphodepletion with cyclophosphamide and fludarabine will occur in the days
      before the IMA201 infusion to improve the duration of time that IMA201 stays in the body.

      After IMA201 infusion, a low dose of IL-2 will be given twice daily for a period of time.

      Since this study involves gene therapy, patients will be monitored throughout the study and
      for up to a total of 15 years.
    

Trial Arms

NameTypeDescriptionInterventions
IMA201 ProductExperimentalPre-conditioning by non-myeloablative chemotherapy with Fludarabine and Cyclophosphamide One dose of IMA201 product will be infused intravenously. Four dose levels will be evaluated. At least two patients per cohort will be treated. Post-infusion of IMA201 product, administration of low-dose recombinant human interleukin-2
  • IMA201 Product

Eligibility Criteria

        Inclusion Criteria:

          -  Signed a written informed consent form(s).

          -  ECOG performance status 0-1.

          -  Women of childbearing potential must use adequate contraception (hormonal or barrier
             method of birth control; abstinence).

        HLA INCLUSIONPathologically confirmed advanced/metastatic solid tumors such as one of the following
        indications:

          -  Pathologically confirmed diagnosis of stage IIIB/IV recurrent NSCLC

          -  Pathologically confirmed diagnosis of stage III/IV recurrent or metastatic HNSCC (oral
             cavity, pharynx, larynx)

        MAIN SCREENING & LEUKAPHERESIS INCLUSION

          -  Pathologically confirmed advanced/metastatic solid tumors such as one of the following
             indications:

               -  Pathologically confirmed diagnosis of stage IIIB/IV recurrent NSCLC

               -  Pathologically confirmed diagnosis of stage III/IV recurrent or metastatic HNSCC
                  (oral cavity, pharynx, larynx)

          -  HLA phenotype positive NOTE: Patients who were previously HLA-typed for participation
             in other Immatics' sponsored clinical trials and were HLA phenotype positive may enter
             IMA201-101 main screening

          -  Patient's tumor must express specified biomarkers. NOTE: Patients who were previously
             screened for participation in other Immatics' sponsored clinical trials and whose
             biomarkers are positive for IMA201-101 based on IMA_Detect may enter IMA201-101
             screening

          -  Recommended acceptable organ and marrow function, defined per protocol

          -  Measurable disease

          -  At least one lesion (metastasis or primary tumor) being considered accessible for a
             biopsy.

          -  Adequate hepatic function, as defined per protocol

          -  Serum creatinine within 1.5 x normal range for age OR creatinine clearance with a
             recommended GFR ≥ 50 mL/min/1.73m2.

          -  Adequate pulmonary function, defined per protocol and oxygen saturation >92% on room
             air.

          -  Acceptable coagulation status: INR ≤2.0 x ULN and PTT ≤2.0 x ULN.

          -  Confirmed availability of production capacities for the patient's ACTengine IMA201
             product prior to the leukapheresis.

        TREATMENT INCLUSION:

        Patients may enter the treatment phase if:

          -  Disease recurs/progresses

          -  Disease becomes refractory or previous anti-cancer treatment is no longer warranted

               -  Available IMA201 T-cell product that was produced for the patient and passed all
                  release tests.

               -  Adequate hepatic function per protocol.

               -  Serum creatinine within 1.5 x normal range for age or creatinine clearance with a
                  recommended GFR ≥ 50 mL/min/1.73m2.

               -  Measurable disease

               -  Male patients must agree to use effective contraception or be abstinent while on
                  study and for 90 days after the infusion of IMA201.

        Exclusion Criteria:

        • Pregnant or is breastfeeding.

        HLA EXCLUSION:

          -  History of other malignancies (except for adequately treated basal or squamous cell
             carcinoma or carcinoma in situ) within the last 3 years.

          -  Serious autoimmune disease

        MAIN SCREENING EXCLUSION:

          -  Any condition contraindicating leukapheresis.

          -  Brain metastases.

          -  HIV infection, active Hepatitis B or C infection

          -  Concomitant therapy indicated with any of the following: interferons or other
             non-study immunotherapy regimens; immunosuppressive agents; other investigational
             therapies; or chronic use of systemic corticosteroids.

          -  Severe immune-related toxicities related to checkpoint inhibitors defined per
             protocol.

          -  Cardiac conditions per protocol

          -  Prior stem cell transplantation or solid organ transplantation.

          -  Concurrent severe and/or uncontrolled medical disease that could compromise
             participation in the study

          -  Active diverticulitis, intra-abdominal abscess or gastrointestinal (GI) obstruction.

          -  History of other malignancies (except for adequately treated basal or squamous cell
             carcinoma or carcinoma in situ) within the last 3 years.

          -  Serious autoimmune disease

          -  History of hypersensitivity to cyclophosphamide, fludarabine or IL-2.

          -  History of or current immunodeficiency disease or prior treatment compromising immune
             function

          -  Patients with active pneumonitis.

          -  Investigator's judgment

        TREATMENT EXCLUSION

          -  Received chemotherapy, surgery, or radiotherapy (for therapeutic purposes) within 3
             weeks (4 weeks for monoclonal antibodies or investigational drugs, 1 week for tyrosine
             kinase inhibitor (TKI) (e.g. erlotinib, gefitinib) or the patient has not recovered
             (from grade ≥2 side effects of the previous therapy) prior to lymphodepletion regimen.

          -  Active pneumonitis.

          -  Patient unable to tolerate lymphodepletion, low-dose IL-2 and/or ACTengine IMA201
             treatment.

          -  Severe immune-related toxicities related to checkpoint inhibitors defined per
             protocol.

          -  Investigator's judgment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events (AE)
Time Frame:up to 15 years post-treatment
Safety Issue:
Description:During treatment and treatment observation phases and long term gene safety follow up, AE and SAE will be captured per CTCAE v4.0. AEs and SAEs will be summarized.

Secondary Outcome Measures

Measure:Duration of infused T cells over time (Persistence of T cells)
Time Frame:Up to 12 months
Safety Issue:
Description:Blood samples will be collected at selected time points (pre- and post-IMA201 treatment at set time points) to assess the persistence of IMA201 T-cells in the blood.
Measure:Incidence of infused T cells (Functionality of T cells)
Time Frame:Up to 12 months
Safety Issue:
Description:
Measure:Success Rates of T cell generation (Feasibility of ACTengine approach)
Time Frame:This endpoint can be evaluated after production of the last patient's specific T-cell product, i.e. after release of the last patient's cell product. Approximately 10 months
Safety Issue:
Description:
Measure:Number of subjects with Clinical response
Time Frame:12 weeks and 24 weeks post IMA201 infusion
Safety Issue:
Description:
Measure:Levels of Blood biomarkers
Time Frame:until the end of the trial, up to 15 years from last patient treatment
Safety Issue:
Description:
Measure:Levels of Tumor biomarkers
Time Frame:until the end of the trial, up to 15 years from last patient treatment
Safety Issue:
Description:
Measure:Rate of successful biomarker tests for tumor samples collected
Time Frame:This can be evaluated after last patient's enrollment, approximately 12 months
Safety Issue:
Description:
Measure:Percentages of patients expressing individual targets
Time Frame:This can be evaluated after last patient's enrollment, approximately 10 months after start of trial.
Safety Issue:
Description:
Measure:Concordance of HLA-A*02:01 Determination assay
Time Frame:This can be evaluated after last patient's enrollment, approximately 10 months after start of trial.
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Immatics US, Inc.

Trial Keywords

  • T-cell therapy
  • immunotherapy
  • adoptive cellular therapy
  • T-Cell Receptor
  • IMA201
  • Cytotherapy
  • Cell Therapy
  • Gene Therapy

Last Updated

January 10, 2020