Clinical Trials /

TCR-engineered T Cells in Solid Tumors Including NSCLC and HCC Patients

NCT03441100

Description:

The study purpose is to establish the safety and tolerability of IMA202 product in patients with solid tumors that express melanoma-associated antigen 1 (MAGEA1).

Related Conditions:
  • Hepatocellular Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: TCR-engineered T Cells in Solid Tumors Including NSCLC and HCC Patients
  • Official Title: Phase 1 Study Evaluating Genetically Modified Autologous T Cells Expressing a T-cell Receptor Recognizing a Cancer/Germline Antigen in Patients With Recurrent and/or Refractory Solid Tumors(ACTengine® IMA202-101)

Clinical Trial IDs

  • ORG STUDY ID: IMA202-101
  • NCT ID: NCT03441100

Conditions

  • Solid Tumor, Adult
  • Cancer
  • Hepatocellular Carcinoma
  • Hepatocellular Cancer
  • Nonsmall Cell Lung Cancer
  • Liver Cancer
  • Lung Cancer

Interventions

DrugSynonymsArms
IMA202 ProductExperimental: IMA202 Product

Purpose

The study purpose is to establish the safety and tolerability of IMA202 product in patients with solid tumors that express melanoma-associated antigen 1 (MAGEA1).

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 IMA202 product.

      MANUFACTURING: IMA202 product will be made from the patient's white blood cells.

      TREATMENT: Lymphodepletion with cyclophosphamide and fludarabine will occur in the days
      before the IMA202 product infusion to improve the duration of time that IMA202 product stays
      in the body. The patient will be admitted to the hospital during the treatment.

      After the IMA202 product 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
Experimental: IMA202 ProductExperimentalPre-conditioning by non-myeloablative chemotherapy with Fludarabine and Cyclophosphamide One dose of IMA202 product will be infused intravenously. Four dose levels will be evaluated. At least two patients per cohort will be treated. Post-infusion of IMA202 product, administration of low dose recombinant human interleukin-2
  • IMA202 Product

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have pathologically confirmed advanced/metastatic solid tumors including
             but not limited to one of the following indications. For patients with other solid
             tumors, there should be evidence of sufficient high likelihood of target expression
             e.g. as the prevalence in the given indication is high or as there is evidence for the
             individual patient from previous assessments that the tumor is target positive. These
             patients should have relapsed and/or refractory solid cancers with no established
             treatment available and they are terminally ill:

          -  Pathologically confirmed diagnosis of stage IIIB/IV recurrent NSCLC OR Pathologically
             or radiologically (fulfilling non-invasive criteria) confirmed diagnosis of HCC not
             amenable to resection (partial hepatectomy or liver transplantation) or local therapy
             with curative intent (e.g. radiofrequency ablation)

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Signed written informed consent form

          -  Women of childbearing potential must use adequate contraception

        MAIN SCREENING:

          -  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
             IMA202-101 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 IMA202-101 based on IMA_Detect may enter IMA202-101
             screening

          -  Adequate 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 for squamous cell NSCLC patients, as defined per protocol.
             For HCC patients: Child-Pugh score ≤6 and Model for End-Stage Liver Disease (MELD)
             score≤15

          -  Serum creatinine within 1.5 x normal range for age OR creatinine clearance with a
             recommended eGFR ≥ 50 mL/min/1.73m^2

          -  Adequate pulmonary function

          -  Acceptable coagulation status

          -  Availability of production capacities for the patient's IMA202 product prior to the
             leukapheresis

        TREATMENT SCREENING:

        These patients should have relapsed and/or refractory solid cancers with no established
        treatment available and they are terminally ill:

          -  Available IMA202 product passed all required release tests

          -  Adequate hepatic function for squamous cell NSCLC patients, as defined per protocol.
             For HCC patients: Child-Pugh score ≤6 and Model for End-Stage Liver Disease (MELD)
             score≤15

          -  Serum creatinine within 1.5 x normal range for age OR creatinine clearance with a
             recommended eGFR ≥ 50 mL/min/1.73m^2

          -  Measurable disease

          -  Male patients must agree to use effective contraception or be abstinent while on study
             and for 90 days after the infusion of IMA202 product

        Exclusion Criteria:

          -  Pregnant or breastfeeding

          -  Serious autoimmune disease

        HLA SCREENING:

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

        MAIN SCREENING:

          -  Any condition contraindicating leukapheresis

          -  Brain metastases. Note: Patients with a history of brain metastases may be eligible,
             if an imaging scan with contrast enhancement not older than 4 weeks is able to exclude
             the existence of currently active brain metastasis

          -  HIV infection, active hepatitis B or C infection. History of treated hepatitis B or C
             is permitted if the viral load is undetectable. HCC patients with controlled or
             chronic stable HBV infection will be eligible for screening. HCC patients with HBV
             infections who are not on anti-HBV treatment will be excluded from the study. HCC
             subjects with HCV infections will be allowed for screening; however, subjects with
             both HBV and HCV infections will be excluded for screening

          -  Patient has received any chemotherapy, surgery, radiotherapy (for therapeutic
             purposes), tyrosine kinase inhibitors, investigational drugs, chronic use of systemic
             corticosteroids or statin therapy within 2 weeks prior to the leukapheresis

          -  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

          -  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 hypersensitivity to cyclophosphamide, fludarabine or IL-2

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

          -  Patients with active pneumonitis

        TREATMENT SCREENING:

          -  Patient received chemotherapy, surgery, or radiotherapy (for therapeutic purposes)
             within 3 weeks, monoclonal antibodies or investigational drugs within 4 weeks or
             tyrosine kinase inhibitor within 1 week, or the patient has not recovered prior to
             lymphodepletion regimen. Note: Patient may be still eligible if the patient has not
             fully recovered from grade ≥2 toxicities if accumulated toxicities with the
             lymphodepletion therapy are not expected

          -  Active pneumonitis

          -  Patient unable to tolerate lymphodepletion, low-dose IL-2 and/or IMA202 product

          -  Severe immune-related toxicity related to checkpoint inhibitors defined as any Grade 4
             toxicity or Grade 3 toxicity
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of subjects with dose-limiting toxicity (DLT) and adverse events (AE)
Time Frame:6 months to 18 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Assessment of tumor responses and progression based on RECIST 1.1 and immune-related RECIST (irRECIST).
Time Frame:12 and 24 weeks after the infusion of IMA202 product
Safety Issue:
Description:
Measure:Success rate of IMA202 product generation
Time Frame:12 months
Safety Issue:
Description:
Measure:Duration of infused IMA202 product over time
Time Frame:12 months
Safety Issue:
Description:
Measure:Incidence of infused IMA202 product
Time Frame:12 months
Safety Issue:
Description:
Measure:Blood based assessment to evaluate the mechanisms of action of IMA202 product
Time Frame:24 months
Safety Issue:
Description:
Measure:Blood based assessment to evaluate the pharmacodynamics of IMA202 product
Time Frame:24 months
Safety Issue:
Description:
Measure:Assessment of tumor biomarker expression levels
Time Frame:24 months
Safety Issue:
Description:
Measure:Assessment of T-cell infiltration
Time Frame:24 months
Safety Issue:
Description:
Measure:Rate of successful biomarker tests for tumor samples collected
Time Frame:24 months
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
  • Cell Therapy
  • Cytotherapy
  • IMA202

Last Updated

December 12, 2019