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

May 12, 2026 updated by: Immatics US, Inc.

Phase 1/2 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

The study's 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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 IMA203 or IMA203CD8 product.

MANUFACTURING: IMA203 or 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, if applicable, a low dose of IL-2 will be given subcutaneously until day 10.

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 Type

Interventional

Enrollment (Estimated)

375

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Germany
      • Berlin, Germany, 12203
        • Recruiting
        • Charité Benjamin Franklin - Klinik für Hämatologie und Onkologie
      • Hamburg, Germany, 20246
        • Recruiting
        • Universitätsklinikum Hamburg-Eppendorf
    • Baden-Wurttemberg
      • Heidelberg, Baden-Wurttemberg, Germany, 69120
        • Recruiting
        • Universitätsklinikum Heidelberg, Nationales Centrum für Tumorerkrankungen (NCT)
    • Bavaria
      • Munich, Bavaria, Germany, 81675
        • Recruiting
        • Klinikum rechts der Isar der Technischen Universität München
        • Contact:
          • Peter Herhaus, MD
      • Würzburg, Bavaria, Germany, 97080
        • Recruiting
        • Universitätsklinikum Würzburg
    • North Rhine-Westphalia
      • Bonn, North Rhine-Westphalia, Germany, 53127
        • Recruiting
        • Universitätsklinikum Bonn - Medizinische Klinik III
    • Rhineland-Palatinate
      • Mainz, Rhineland-Palatinate, Germany, 55131
        • Recruiting
        • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
    • Saxony
      • Dresden, Saxony, Germany, 01307
        • Recruiting
        • Universitätsklinikum C.-G.-Carus Dresden
  • United States
    • California
      • Stanford, California, United States, 94305
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado, Anschutz Medical Campus
        • Contact:
          • Sapna Patel, MD
          • Phone Number: 720-848-0000
    • Florida
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami Hospital and Clinics
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago Medical Center
        • Contact:
          • Katherine Kurnit, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
          • Oldadapo O. Yeku, MD. PhD
          • Phone Number: 617-643-6158
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
    • Ohio
      • Columbus, Ohio, United States, 43026
        • Recruiting
        • Ohio State University Wexner Medical Center Gynecologic Oncology at Mill Run
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Recruiting
        • Fox Chase Cancer Center
        • Principal Investigator:
          • Anthony Olszanski, MD
        • Contact:
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University, Honickman Center
        • Contact:
      • Philadelphia, Pennsylvania, United States, 19104
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • University of Pittsburgh Medical Center
        • Principal Investigator:
          • Jason Luke, M.D.
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas MD Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • Dejka M Araujo, M.D.
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutchinson Cancer Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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-A*02:01 positive
  • For patients with ovarian/fallopian tube cancer only: Patients must have confirmed diagnosis of high-grade serous or endometrioid epithelial ovarian cancer (EOC), primary peritoneal cancer, or fallopian tube cancer.
  • For patients with endometrial carcinoma only: Patients must have a histologically confirmed diagnosis of recurrent or persistent endometrial carcinoma.
  • Measurable disease according to RECIST 1.1
  • Adequate selected organ function per protocol
  • Patient's tumor must express tumor antigen by "IMADetect® RT-qPCR. Retrospective testing will be required for patients that qualify.
  • Life expectancy more than 5 months
  • 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
  • Positive for HIV infection or with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
  • Patients with LDH greater than 2.0-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.).

Other protocol defined inclusion/exclusion criteria could apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Other Names:
  • anzutresgene autoleucel
  • anzu-cel
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.
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.
Experimental: Extension Cohort C
IMA203CD8 at dose levels confirmed to be safe
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.
Experimental: Extension Cohort D
IMA203CD8 at dose levels confirmed to be safe; without IL-2
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.
Experimental: Head and Neck, Lung, and Triple Negative Breast Cancer
IMA203CD8 monotherapy at dose levels confirmed to be safe
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.
Experimental: Dose Escalation A (closed to enrollment)
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
Other Names:
  • anzutresgene autoleucel
  • anzu-cel
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.
Experimental: Extension Cohort B (closed to enrollment)
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
Other Names:
  • anzutresgene autoleucel
  • anzu-cel
Drug: Nivolumab
Nivolumab will be given post IMA203/IMA203CD8 infusion, after hematologic recovery is achieved. Clinical supply provided by Bristol Myers Squibb.
Other Names:
  • Opdivo®
Experimental: Extension Cohort AA
IMA203 at final RP2D (flat dose)
Biological: IMA203 product- flat dose
The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells
Other Names:
  • anzutresgene autoleucel
  • anzu-cel
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.
Experimental: Uveal Melanoma
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
Other Names:
  • anzutresgene autoleucel
  • anzu-cel
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.
Experimental: Ovarian
IMA203CD8 monotherapy at dose levels confirmed to be safe
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.
Experimental: Endometrial
IMA203CD8 monotherapy at dose levels confirmed to be safe
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.
Experimental: Rare Cancers
IMA203CD8 monotherapy at dose levels confirmed to be safe
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1: Determine the MTD and/or recommended dose for extension for IMA203/IMA203CD8
Time Frame: 28 days
Number of patients with dose-limiting toxicities (DLTs)
28 days
Phase 1 and Phase 2: Tumor Response
Time Frame: 5 years
Objective response rate (ORR) based on best overall response (BOR) of complete response (CR) and partial response (PR) centrally assessed (by a BICR1) using RECIST1.1
5 years
Phase 1 and Phase 2: Number and grade of treatment emergent adverse events and adverse events of special interest in subjects treated.
Time Frame: 35 days
Treatment emergent adverse events (TEAEs), Adverse events of special interest (AESIs) and Treatment-emergent serious adverse events (TESAEs).
35 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1 and 2: Persistence of TCR engineered T-cells
Time Frame: up to 5 years post treatment
Measurement of TCR-engineered T cells in peripheral blood
up to 5 years post treatment
Phase 1 and 2: Tumor response
Time Frame: up to 5 years
Overall response rate, duration of response, disease control rate and progression free survival based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Overall survival.
up to 5 years
Phase 2: Patient reported quality of life
Time Frame: up to 5 years
Quality of Life questionnaires (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and EuroQol 5-Dimension 5-Level questionnaire). Higher score indicates worsening of patient's condition.
up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Immatics US, Inc.

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 14, 2019

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

June 1, 2032

Study Registration Dates

First Submitted

September 25, 2018

First Submitted That Met QC Criteria

September 25, 2018

First Posted (Actual)

September 26, 2018

Study Record Updates

Last Update Posted (Actual)

May 13, 2026

Last Update Submitted That Met QC Criteria

May 12, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IMA203-101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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