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History of Changes for Study: NCT03686124
ACTengine® IMA203/IMA203CD8 as Monotherapy or in Combination With Nivolumab in Recurrent and/or Refractory Solid Tumors (ACTengine)
Latest version (submitted October 23, 2023) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 September 25, 2018 None (earliest Version on record)
2 October 4, 2018 Study Status
3 March 14, 2019 Study Status and Oversight
4 April 22, 2019 Recruitment Status, Study Status and Contacts/Locations
5 April 26, 2019 Contacts/Locations and Study Status
6 June 6, 2019 Study Status
7 June 21, 2019 Contacts/Locations and Study Status
8 July 12, 2019 Contacts/Locations and Study Status
9 December 12, 2019 Study Status and Study Description
10 January 10, 2020 Study Status
11 February 26, 2020 Study Status and Contacts/Locations
12 August 12, 2020 Outcome Measures, Arms and Interventions, Contacts/Locations, Study Status, Study Design, Eligibility, Study Description, Sponsor/Collaborators and Study Identification
13 September 3, 2020 Study Status and Contacts/Locations
14 April 8, 2021 Study Status and Contacts/Locations
15 July 7, 2021 Arms and Interventions, Contacts/Locations, Study Description, Study Status, Eligibility, Study Design and Study Identification
16 August 19, 2021 Study Status and Contacts/Locations
17 September 10, 2021 Contacts/Locations and Study Status
18 May 24, 2022 Arms and Interventions, Study Status, Outcome Measures, Study Description, Study Identification and Eligibility
19 August 11, 2022 Outcome Measures, Arms and Interventions, Contacts/Locations, Study Description, Study Status, Eligibility, Study Design and Study Identification
20 February 2, 2023 Study Status and Contacts/Locations
21 August 21, 2023 Arms and Interventions, Contacts/Locations, Study Status, Eligibility, Study Design, Conditions and Study Description
22 October 23, 2023 Study Status and Contacts/Locations
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Changes (Merged) for Study: NCT03686124
September 25, 2018 (v1) -- October 23, 2023 (v22)

Changes in: Study Identification, Study Status, Sponsor/Collaborators, Oversight, Study Description, Conditions, Study Design, Arms and Interventions, Outcome Measures, Eligibility and Contacts/Locations

Open or close this module Study Identification
Unique Protocol ID: IMA203-101
Brief Title: TCR-engineered T Cells in Solid Tumors (ACTengine) ACTengine® IMA203/IMA203CD8 as Monotherapy or in Combination With Nivolumab in Recurrent and/or Refractory Solid Tumors (ACTengine)
Official Title: Phase 1 Study Evaluating Genetically Modified Autologous T Cells Expressing a T-cell Receptor TCR Recognizing a Cancer/Germline Antigen as Monotherapy or in Combination With Nivolumab in Patients With Relapsed Recurrent and/or Refractory Solid Tumors (ACTengine IMA203-101) Tumors
Secondary IDs:
Open or close this module Study Status
Record Verification: September 2018 October 2023
Overall Status: Not yet recruiting Recruiting
Study Start: March 2019 May 14, 2019
Primary Completion: January 2021 December 2028 [Anticipated]
Study Completion: January 2035 December 2028 [Anticipated]
First Submitted: September 25, 2018
First Submitted that
Met QC Criteria:
September 25, 2018
First Posted: September 26, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:
September 25, 2018 October 23, 2023
Last Update Posted: September 26, 2018 [Actual] October 25, 2023 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Immatics US, Inc.
Responsible Party: Sponsor
Collaborators: M.D. Anderson Cancer Center
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: Yes
Unapproved/Uncleared Device: Yes
Pediatric Postmarket Surveillance:
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: The study purpose is to establish the safety and tolerability of IMA 203 product 203/IMA203CD8 products with or without combination with nivolumab in patients with solid tumors tumors that express preferentially expressed antigen in melanoma (PRAME).
Detailed Description:

SCREENING: Patient eligibility will be determined by protocol inclusion/exclusion criteria including HLA (human leukocyte antigen) screening and a biopsy (or collection of archival tumor tissue) for biomarker screening. If the patient is eligible, white blood cells will be taken during leukapheresis for the manufacture of the an IMA203 or an IMA203CD8 product.

MANUFACTURING: IMA203 product and IMA203CD8 products will be made from the patient patients&apos ;s ; white blood cells.

TREATMENT: Lymphodepletion with cyclophosphamide and fludarabine will occur in the days before the IMA 203 203/IMA203CD8 product infusion to improve the duration of time that IMA 203 203/IMA203CD8 product stays in the body. The patient will be admitted to the hospital during the treatment T-cell infusion.

After the IMA 203 203/IMA203CD8 product infusion, a low dose of IL-2 will be given subcutaneously twice daily for 14 10 days.

Since this study involves gene therapy, patients will be monitored throughout the study and for up to a total of 15 years. In Extension Cohort B (IMA203) nivolumab will be administered intravenously.

Patients will be monitored closely throughout the study. The follow-up phase ends 5 years post infusion.

Open or close this module Conditions
Conditions: Refractory Cancer
Recurrent Cancer
Solid Tumor, Adult
Cancer
Keywords: T-cell therapy
immunotherapy
Melanoma (Skin)
Melanoma, Uveal
Ovarian Carcinoma
Uterine Carcinoma
Uterine Carcinosarcoma
Immatics
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Single Group Assignment Parallel Assignment
Number of Arms: 1 5
Masking: None (Open Label)
Allocation: N/A Non-Randomized
Enrollment: 16 186 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: IMA203 Product Experimental: Dose Escalation A
  • Pre-conditioning by non-myeloablative chemotherapy with Fludarabine and Cyclophosphamide Dose escalation of IMA203
  • One dose of IMA203 product will be infused intravenously. Four dose levels will be evaluated. At least two patients per cohort will be treated.
  • Post-infusion of IMA203 product, administration of low dose recombinant human interleukin-2
  • Biological: IMA203 Product
    Four dose levels (DL) of IMA203 product will be evaluated. The cell dose will be based on viable CD3+CD8+ HLA-Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula.
    Device: IMADetect®
    IMADetect IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials. IMADetect IMADetect® is intended for investigational use only.
    Experimental: Extension Cohort A
    IMA203 at RP2D
    Biological: IMA203 Product
    The cell dose will be based on viable CD3+CD8+ HLA-Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula.
    Device: IMADetect®
    IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials. IMADetect® is intended for investigational use only.
    Experimental: Extension Cohort B
    IMA203 at RP2D + nivolumab
    Biological: IMA203 Product
    The cell dose will be based on viable CD3+CD8+ HLA-Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula.
    Device: IMADetect®
    IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials. IMADetect® is intended for investigational use only.
    Drug: nivolumab (Opdivo®)
    Nivolumab will be given post IMA203 infusion, after hematologic recovery is achieved. Clinical supply provided by Bristol Myers Squibb.
    Other Names:
    • Opdivo®
    Experimental: Extension Cohort C
    IMA203CD8 at provisional RP2D
    Biological: IMA203CD8 Product
    The cell dose will be based on viable CD3+CD8+ HLA-Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula.
    Device: IMADetect®
    IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials. IMADetect® is intended for investigational use only.
    Experimental: Dose Escalation B
    Dose escalation of IMA203CD8
    Biological: IMA203CD8 Product
    The cell dose will be based on viable CD3+CD8+ HLA-Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula.
    Device: IMADetect®
    IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials. IMADetect® is intended for investigational use only.
    Open or close this module Outcome Measures
    Primary Outcome Measures:
    1. Evaluate safety and tolerability of treatment with treatment with ACTengine® IMA203/IMA203CD8 products as monotherapy or in combination with nivolumab
    [ Time Frame: 35 days ]

    Treatment emergent adverse events
    1 . Number of subjects with dose-limiting toxicity (DLT)
    [ Time Frame: 3 weeks ]

    2. Number of treatment-emergent adverse events Determine the MTD and/or recommended dose for extension for IMA203/IMA203CD8
    [ Time Frame: up to 12 months 28 days ]

    Number of patients with dose-limiting toxicities (DLTs)
    3 . Number of treatment-emergent adverse events of special interest
    [ Time Frame: up to 12 months ]

    4 . Number of treatment-emergent serious adverse events
    [ Time Frame: up to 12 months ]

    5 . Recommended Phase 2 Dose (RP2D)
    [ Time Frame: end of accrual, approximately 12 months ]

    Secondary Outcome Measures:
    1. Duration of tumor response Persistence of T-cells
    [ Time Frame: up to 12 months up to 5 years post treatment ]

    Measurement of TCR-engineered T cells in peripheral blood
    2. Frequency of TCR engineered T cells within blood T cells Tumor response
    [ Time Frame: Up up to 12 months ]

    Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
    3. Tumor response
    [ Time Frame: up to 12 months ]

    Immune-Related Response Evaluation Criteria In Solid Tumors (irRECIST)
    Open or close this module Eligibility
    Minimum Age: 18 Years
    Maximum Age:
    Sex: All
    Gender Based:
    Accepts Healthy Volunteers: No
    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.
    • 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 ≥ 60 mL/min/1.73 m2
    • 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.
    • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
    • HLA phenotype positive HLA phenotype positive for the study
    • Measurable disease Measurable disease according to RECIST 1.1
    • Adequate pulmonary selected organ function per protocol
    • Patient's tumor must express tumor antigen by qPCR using a tumor biopsy specimen OR be a tumor type with at least 95% known prevalence of protocol-specific antigen expression Patient's tumor must express tumor antigen by "IMADetect® RT-qPCR
    • Life expectancy more than 3 months
    • For hepatocellular carcinoma (HCC) patients only, Child-Pugh score of ≤ 6 and model for end-stage liver disease (MELD) score ≤ 15
    • IMA203 product must have passed all of the release tests
    • Female patient of childbearing potential must use adequate contraception prior to study entry until 6 12 months after the infusion of IMA203/IMA203CD8
    • Male patient must agree to use effective contraception or be abstinent while on study and for 90 days 6 months after the infusion of IMA203/IMA203CD8
    • The patient must have recovered from any side effects of prior therapy to Grade 1 or lower prior to lymphodepletion.

    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
    • Positive for HIV infection or with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
    • Patients with LDH greater than 2.5-fold ULN.
    • Any condition contraindicating leukapheresis, lymphodepletion, low-dose IL-2, and/or IMA203/IMA203CD8 treatment
    • Patients with active brain metastases
    • Concurrent treatment in another clinical trial.
    • For nivolumab treatment, patients 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.).
    • HIV infection, active hepatitis B or C infection. History of treated hepatitis B or C is permitted if the viral load is undetectable per qPCR and or nucleic acid testing.

    Other protocol defined inclusion/exclusion criteria could apply

    Note: HCC patients with controlled hepatitis B virus (HBV) infection as defined by subjects with resolved (anti-surface antigen [HBs-Ag] antibody negative, anti-core antigen [HBc Ag] antibody positive) or chronic stable (anti HBs-Ag antibody positive HBV) 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 hepatitis C virus (HCV) infections will be allowed for screening; however, subjects with both HBV and HCV infections will be excluded for screening.

    • 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.

    • Treatment with protocol-defined excluded treatments, medical devices, and/or procedures per protocol
    • The patient has not recovered from any grade 2 or greater side effect of prior therapy to grade 2 or lower (except for non-clinically significant toxicities, e.g., alopecia, vitiligo) prior to lymphodepletion.
    Open or close this module Contacts/Locations
    Central Contact Person: Rebecca Griffith-Eskew Immatics US, Inc.
    Telephone: 346- +1 346 204- 5359 5400
    Email: griffith-eskew ctgovinquiries@immatics.com
    Study Officials: Apostolia Tsimberidou, M.D., Ph.D. Cedrik Britten, M.D.
    Principal Investigator Study Director
    MDACC, Houston, TX Immatics US, Inc.
    Locations: United States, Florida
    University of Miami Hospital and Clinics
    [Recruiting]
    Miami, Florida, United States, 33136
    Contact:Contact: 305-243-2647 CRSCutaneous@miami.edu
    United States, New York
    Columbia University Medical Center
    [Recruiting]
    New York, New York, United States, 10032
    Contact:Contact: 212-342-5162 cancerclinicaltrials@cumc.columbia.edu
    Contact:Principal Investigator: Ran Reshef, MD
    United States, Pennsylvania
    University of Pittsburgh Medical Center
    [Recruiting]
    Pittsburgh, Pennsylvania, United States, 15232
    Contact:Contact: Jason Luke, M.D. 412-623-6132 lukejj@upmc.edu
    Contact:Principal Investigator: Jason Luke, M.D.
    United States, Texas
    University of Texas MD Anderson Cancer Center
    [Recruiting]
    Houston, Texas, United States, 77030
    Contact:Contact: Apostolia Tsimberidou Dejka M Araujo, M.D. 713-792-3626 daraujo@mdanderson.org
    Contact:Principal Investigator: Dejka M Araujo, Ph M.D.
    Germany
    Charité Benjamin Franklin - Klinik für Hämatologie und Onkologie
    [Recruiting]
    Berlin, Germany, 12203
    Universitätsklinikum Hamburg-Eppendorf
    [Recruiting]
    Hamburg, Germany, 20246
    Germany, Bavaria
    Universitätsklinikum Würzburg
    [Recruiting]
    Würzburg, Bavaria, Germany, 97080
    Germany, North Rhine-Westphalia
    Universitätsklinikum Bonn - Medizinische Klinik III
    [Recruiting]
    Bonn, North Rhine-Westphalia, Germany, 53127
    Germany, Saxony
    Universitätsklinikum C.-G.-Carus Dresden
    [Recruiting]
    Dresden, Saxony, Germany, 01307
    Open or close this module IPDSharing
    Plan to Share IPD:
    Open or close this module References
    Citations:
    Links:
    Available IPD/Information:

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