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ACTengine® IMA203/IMA203CD8 as Monotherapy or in Combination With Nivolumab in Recurrent and/or Refractory Solid Tumors

Sponsor
Immatics US, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03686124
Collaborator
(none)
102
Enrollment
8
Locations
4
Arms
114.6
Anticipated Duration (Months)
12.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study purpose is to establish the safety and tolerability of IMA203/IMA203CD8 products with or without combination with nivolumab in patients with solid tumors that express preferentially expressed antigen in melanoma (PRAME).

Condition or Disease Intervention/Treatment Phase
  • Biological: IMA203 Product
  • Biological: IMA203CD8 Product
  • Device: IMADetect®
  • Drug: nivolumab (Opdivo®)
 Phase 1

Detailed Description

SCREENING: Patient eligibility will be determined by protocol inclusion/exclusion criteria including 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 an IMA203 or an IMA203CD8 product.

MANUFACTURING: IMA203 and IMA203CD8 products will be made from the patients' white blood cells.

TREATMENT: Lymphodepletion with cyclophosphamide and fludarabine will occur in the days before the IMA203/IMA203CD8 product infusion to improve the duration of time that IMA203/IMA203CD8 product stays in the body. The patient will be admitted to the hospital during the T-cell infusion.

After the IMA203/IMA203CD8 product infusion, a low dose of IL-2 will be given subcutaneously daily for 10 days.

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
102 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1 Study Evaluating Genetically Modified Autologous T Cells Expressing a TCR Recognizing a Cancer/Germline Antigen as Monotherapy or in Combination With Nivolumab in Patients With Recurrent and/or Refractory Solid Tumors
Actual Study Start Date :
May 14, 2019
Anticipated Primary Completion Date :
Dec 1, 2028
Anticipated Study Completion Date :
Dec 1, 2028

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose Escalation

Dose escalation of IMA203

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 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.

    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 [35 days]

      Treatment emergent adverse events

    2. Determine the MTD and/or recommended dose for extension for IMA203/IMA203CD8 [28 days]

      Number of patients with dose-limiting toxicities (DLTs)

    Secondary Outcome Measures

    1. Persistence of T-cells [up to 5 years post treatment]

      Measurement of TCR-engineered T cells in peripheral blood

    2. Tumor response [up to 12 months]

      Response Evaluation Criteria In Solid Tumors (RECIST) 1.1

    3. Tumor response [up to 12 months]

      Immune-Related Response Evaluation Criteria In Solid Tumors (irRECIST)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • 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 for the study

    • Measurable disease according to RECIST 1.1

    • Adequate selected organ function per protocol

    • Patient's tumor must express tumor antigen by "IMADetect® RT-qPCR

    • Life expectancy more than 3 months

    • 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.

    • Female patient of childbearing potential must use adequate contraception prior to study entry until 12 months after the infusion of IMA203/IMA203CD8

    • Male patient must agree to use effective contraception or be abstinent while on study and for 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

    • 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 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

    • Patients who have received more than 4 prior systemic treatment lines for treatment of advanced and/or metastatic disease.

    • Patients who are known to have at least one single tumor lesion that exceeds 10 cm in diameter

    • Any condition contraindicating leukapheresis, lymphodepletion, low-dose IL-2, and/or IMA203/IMA203CD8 treatment

    • Patients with active brain metastases

    • Concurrent participation in an interventional part of 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.).

    Other protocol defined inclusion/exclusion criteria could apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Columbia University Medical Center New York New York United States 10032
    2 University of Pittsburgh Medical Center Pittsburgh Pennsylvania United States 15232
    3 University of Texas MD Anderson Cancer Center Houston Texas United States 77030
    4 Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11 Regensburg Bavaria Germany 93053
    5 Universitätsklinikum Würzburg Würzburg Bavaria Germany 97080
    6 Universitätsklinikum Bonn - Medizinische Klinik III Bonn North Rhine-Westphalia Germany 53127
    7 Universitätsklinikum C.-G.-Carus Dresden Dresden Saxony Germany 01307
    8 Universitätsklinikum Hamburg-Eppendorf Hamburg Germany 20246

    Sponsors and Collaborators

    • Immatics US, Inc.

    Investigators

    • Study Director: Cedrik Britten, M.D., Immatics US, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Immatics US, Inc.
    ClinicalTrials.gov Identifier:
    NCT03686124
    Other Study ID Numbers:
    • IMA203-101
    First Posted:
    Sep 26, 2018
    Last Update Posted:
    Aug 15, 2022
    Last Verified:
    Aug 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    Yes
    Keywords provided by Immatics US, Inc.
    T-cell therapy
    immunotherapy
    Additional relevant MeSH terms:
    Recurrence
    Nivolumab

    Study Results

    No Results Posted as of Aug 15, 2022