Clinical Trials /

TCR-engineered T Cells in Solid Tumors

NCT03686124

Description:

The study purpose is to establish the safety and tolerability of IMA203 product in patients with solid tumors that express preferentially expressed antigen in melanoma (PRAME).

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: TCR-engineered T Cells in Solid Tumors
  • Official Title: Phase 1 Study Evaluating Genetically Modified Autologous T Cells Expressing a T-cell Receptor Recognizing a Cancer/Germline Antigen as Monotherapy or in Combination With Atezolizumab in Patients With Recurrent and/or Refractory Solid Tumors (ACTengine IMA203-101)

Clinical Trial IDs

  • ORG STUDY ID: IMA203-101
  • NCT ID: NCT03686124

Conditions

  • Refractory Cancer
  • Recurrent Cancer
  • Solid Tumor, Adult
  • Cancer

Interventions

DrugSynonymsArms
IMA203 ProductIMA203 Product
AtezolizumabTecentriqIMA203 Product + atezolizumab

Purpose

The study purpose is to establish the safety and tolerability of IMA203 product in patients with solid tumors that express preferentially expressed antigen in melanoma (PRAME).

Detailed Description

      SCREENING: Patient eligibility will be determined by HLA (human leukocyte antigen) screening
      and a biopsy for biomarker screening. If the patient is eligible, white blood cells will be
      taken during leukapheresis for the manufacture of the IMA203 product.

      MANUFACTURING: IMA203 product will be made from the patient's white blood cells.

      TREATMENT: Lymphodepletion with cyclophosphamide and fludarabine will occur in the days
      before the IMA203 product infusion to improve the duration of time that IMA203 product stays
      in the body. The patient will be admitted to the hospital during the T-cell infusion.

      After the IMA203 product infusion, a low dose of IL-2 will be given subcutaneously twice
      daily for 14 days.

      In group 2, atezolizumab will be administered every 4 weeks.

      Patients will be monitored closely throughout the study. The treatment and observation phase
      ends 3 years post infusion.
    

Trial Arms

NameTypeDescriptionInterventions
IMA203 ProductExperimentalPre-conditioning by non-myeloablative chemotherapy with Fludarabine and Cyclophosphamide One dose of IMA203 product will be infused intravenously. Three dose levels will be evaluated. At least three patients per cohort will be treated. Post-infusion of IMA203 product, administration of low dose recombinant human interleukin-2
  • IMA203 Product
IMA203 Product + atezolizumabExperimentalPre-conditioning by non-myeloablative chemotherapy with Fludarabine and Cyclophosphamide One dose of IMA203 product will be infused intravenously. Two dose levels will be evaluated. At least three patients per cohort will be treated. Post-infusion of IMA203 product, administration of low dose recombinant human interleukin-2 Treatment with atezolizumab: starting 2 lower doses every 2 weeks, followed by every 4 weeks for 1 year
  • IMA203 Product
  • Atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Pathologically confirmed advanced and/or metastatic solid tumor

          -  Patients may enter screening procedure before, during, or after the last available
             indicated standard of care treatment. There is no limitation for prior anti cancer
             treatments.

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

          -  HLA phenotype positive

          -  Measurable disease and accessible to biopsy

          -  Adequate pulmonary function per protocol

          -  Acceptable organ and bone marrow function per protocol

          -  Acceptable coagulation status per protocol

          -  Adequate hepatic function per protocol

          -  Serum creatinine within normal range for age OR creatinine clearance with a
             recommended estimated glomerular filtration rate ≥ 50 mL/min/1.73 m2

          -  Patient's tumor must express tumor antigen by qPCR using a fresh tumor biopsy specimen

          -  Life expectancy more than 3 months

          -  Confirmed availability of production capacities for IMA203 product

          -  Patients must have recurrent/progressing and/or refractory solid tumors and must have
             received or not be eligible for all available indicated standard of care treatment.

          -  For hepatocellular carcinoma (HCC) patients only, Child-Pugh score of ≤ 6

          -  IMA203 product must have passed all of the release tests

          -  Female patient of childbearing potential must use adequate contraception prior to
             study entry until 12 months after the infusion of IMA203

          -  Male patient must agree to use effective contraception or be abstinent while on study
             and for 6 months after the infusion of IMA203

          -  Hepatocellular carcinoma (HCC) patients with liver cirrhosis only - upper endoscopy is
             required within 6 months of study entry

          -  The patient must have recovered from any side effects of prior therapy to Grade 1 or
             lower (except for non-clinically significant toxicities; e.g., alopecia, vitiligo)
             prior to lymphodepletion. As determined by the investigator, the patient may still be
             eligible if the patient has not fully recovered from Grade ≥ 2 toxicities if these
             toxicities are not anticipated to further improve (e.g., chronic neuropathy) and such
             toxicities are not anticipated to worsen with the lymphodepletion therapy

        Exclusion Criteria:

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

          -  Solid tumors with low likelihood of tumor biomarker expression per protocol

          -  Pregnant or breastfeeding

          -  Serious autoimmune disease Note: At the discretion of the investigator, these patients
             may be included if their disease is well controlled without the use of
             immunosuppressive agents.

          -  History of cardiac conditions as per protocol

          -  Prior stem cell transplantation or solid organ transplantation

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

          -  History of hypersensitivity to cyclophosphamide (CY), fludarabine (FLU), or IL-2

          -  History of or current immunodeficiency disease or prior treatment compromising immune
             function at the discretion of the treating physician

          -  HIV infection, active hepatitis B virus (HBV), active hepatitis C virus (HCV)
             infection, ongoing active anti-HCV treatment or detectable HBV or HCV viral load at
             the most recent laboratory report. Patients with both HBV and HCV infections will be
             excluded from screening

               1. Patients with a history of HCV infection and with an undetectable viral load per
                  the most recent laboratory report and/or completed anti-HCV treatment but are HCV
                  antibody positive are permitted.

               2. History of treated HBV infection is permitted if the viral load is undetectable
                  per the most recent laboratory report. Note: HCC patients with controlled HBV
                  infection, as defined by resolved (anti-hepatitis B surface antigen [HBs-Ag]
                  antibody (Ab) negative, anti-core antigen [HBc Ag] Ab positive) or chronic stable
                  (anti HBs-Ag Ab positive) HBV infection will be eligible for screening. Patients
                  with active HBV infection who are not on anti-HBV treatment will be excluded.

          -  Any condition contraindicating leukapheresis

          -  Patients with active 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, and steroid therapy has been discontinued for ≥2 weeks.

        • Treatment with protocol-defined excluded treatments, medical devices, and/or procedures
        per protocol

        For atezolizumab treatment, patients must have adequate hematologic recovery, must have
        recovered from infections to Grade 1 or lower, and must not have a history of severe
        immune-related toxicities, defined as any Grade 3 or 4 toxicities related to prior
        PD1/PD-L1 inhibitor therapy (e.g., atezolizumab, pembrolizumab or nivolumab etc.).
      
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 3 years post treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Persistence of T-cells
Time Frame:up to 3 years post treatment
Safety Issue:
Description:
Measure:Tumor response per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and immune-related RECIST (irRECIST)
Time Frame:up to 12 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

Last Updated

September 7, 2020