Clinical Trials /

TCR-engineered T Cells in Solid Tumors With Emphasis on NSCLC and HNSCC (ACTengine)

NCT03247309

Description:

The study purpose is to establish the safety and tolerability of IMA201 in patients with solid tumors.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Nasopharyngeal Squamous Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: TCR-engineered T Cells in NSCLC and HNSCC Patients (ACTengine)
  • Official Title: Phase I Trial Evaluating Genetically Modified Autologous T Cells Expressing a T-Cell Receptor Recognizing a Cancer/Germline Antigen in Patients With Squamous Cell Non-small Cell Lung Cancer or Head and Neck Squamous Cell Carcinoma

Clinical Trial IDs

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

Conditions

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

Interventions

DrugSynonymsArms
IMA201 T-CellsIMA201 T-Cells
FludarabineFludarabine MonophosphateIMA201 T-Cells
CyclophosphamideCytoxanIMA201 T-Cells
Recombinant human interleukin-2Aldesleukin, ProleukinIMA201 T-Cells

Purpose

This clinical research study investigates IMA201 which is composed of special immune cells (T cells, also called T lymphocytes) being genetically modified by introduction of a tumor-antigen specific T cell receptor (TCR) to fight against cancer. Patients that choose to take part in this study have advanced cancer where there is no (further) standard treatment for their cancer available OR current treatments are not tolerated. The main purpose of this clinical research study is to confirm the safety of IMA201 and to define the highest safe dose of IMA201 cells to give to patients. The study will also investigate what the specific side effects of this treatment are, and to see whether this therapy shows clinical activity in patients with their advanced cancer.

Detailed Description

      SCREENING: First, the patient will have 2 sets of screening tests to determine eligibility:
      HLA (human leukocyte antigen) screening and Main screening. After both screenings are
      completed and if the patient is eligible, blood will be taken for the manufacture of IMA201.

      The HLA screening test will be done by an investigational device. Patients must have the
      HLA-A*02:01 subtype to continue to the Main screening of the study. The Main screening will
      include medical tests and exams, including a tumor biopsy that will be tested for specific
      biomarkers by an investigational device called IMA201_Detect. Patients must be positive for
      at least one of the study's biomarkers to continue onto the leukapheresis part of the study.

      Manufacturing phase: From the patient's blood collected at the leukapheresis, the
      investigators will make the IMA201 TCR-engineered T cells. In order to insert the new gene
      into the patient's T-cells, investigators will use a gene transfer technology. This will be
      done with a lentiviral vector derived from a virus. The vector was made specifically for this
      study and will carry the TCR genes into the T cells.

      TREATMENT: In other clinical studies using T cells, some investigators found that giving
      chemotherapy before the T cell infusion can improve the amount of time the T cells stay in
      the body. Giving chemotherapy before a T cell infusion is called lymphodepletion. The
      chemotherapy used for lymphodepletion in this study will be a combination of cyclophosphamide
      and fludarabine which would be given in the days before the IMA201 T cell infusion. Two days
      after the last chemotherapy dose, the patient will be admitted to the hospital the night
      before the IMA201 infusion. The IMA201 treatment will be given at MD Anderson Cancer Center.

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

Eligibility Criteria

        Inclusion Criteria:

        HLA SCREENING Inclusion:

          -  Signed a written informed consent form.

          -  Pathologically confirmed diagnosis of stage IIIB/IV recurrent squamous cell NSCLC who
             has received systemic therapy. OR Pathologically confirmed diagnosis of stage III/IV
             recurrent or metastatic HNSCC (oral cavity, pharynx, larynx) who had received systemic
             therapy.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

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

        MAIN SCREENING INCLUSION

          -  Signed a written informed consent form.

          -  Pathologically confirmed diagnosis of stage IIIB/IV recurrent squamous cell NSCLC
             defined as not amenable to local curative therapy (surgery, radiation, or
             chemoradiation), and refractory to systemic therapy, including previous treatment as
             defined per protocol.

        OR

          -  Pathologically confirmed diagnosis of stage III/IV recurrent or metastatic HNSCC (oral
             cavity, pharynx, larynx) not amenable to local therapy with curative intent (surgery,
             radiation therapy, or chemoradiation) including previous treatment defined per
             protocol.

          -  HLA phenotype HLA-A*02:01.

          -  Patient's tumor must express specified biomarkers

          -  ECOG performance status 0-1.

          -  Normal 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 ≤1.5 x ULN and PTT ≤1.5 x ULN.

          -  Women of childbearing potential must use adequate contraception (hormonal or barrier
             method of birth control; abstinence) prior to study entry until 6 months after the
             infusion of IMA201.

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

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

        TREATMENT INCLUSION:

          -  Signed informed consent form

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

          -  ECOG performance status 0-1.

          -  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.

          -  Women of childbearing potential must use adequate contraception (hormonal or barrier
             method of birth control; abstinence) prior to study entry until 6 months after the
             infusion of IMA201.

          -  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:

        HLA EXCLUSION:

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

          -  Pregnant or is breastfeeding.

          -  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 toxicity related to checkpoint inhibitors defined as any Grade 4
             toxicity or Grade 3 toxicity requiring corticosteroid treatment for longer than 12
             weeks.

          -  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.

          -  Pregnant or is breastfeeding.

          -  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.

        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.

          -  Pregnant or breastfeeding.

          -  Active pneumonitis.

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

          -  Severe immune-related toxicity related to checkpoint inhibitors defined as any Grade 4
             toxicity or Grade 3 toxicity requiring corticosteroid treatment for longer than 12
             weeks.
      
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
  • HLA-A*02:01
  • adoptive cellular therapy
  • T-Cell Receptor

Last Updated

September 26, 2017