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

NCT03686124 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: IMA203-101
• Study Type: interventional
• Target: 375
• Locations: 2 countries
• Sites: 21

Brief Summary

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).

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

Outcome Measures

Primary Outcomes (3)

• Phase 1: Determine the MTD and/or recommended dose for extension for IMA203/IMA203CD8

  Number of patients with dose-limiting toxicities (DLTs)

  28 days

• Phase 1 and Phase 2: Number and grade of treatment emergent adverse events and adverse events of special interest in subjects treated.

  Treatment emergent adverse events (TEAEs), Adverse events of special interest (AESIs) and Treatment-emergent serious adverse events (TESAEs).

  35 days

• Phase 1 and Phase 2: Tumor Response

  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

Secondary Outcomes (3)

• Phase 1 and 2: Persistence of TCR engineered T-cells

  up to 5 years post treatment

• Phase 1 and 2: Tumor response

  up to 5 years

• Phase 2: Patient reported quality of life

  up to 5 years

Study Arms (12)

Dose Escalation A (closed to enrollment)

EXPERIMENTAL

Dose escalation of IMA203

Biological: IMA203 Product; Device: IMADetect®

Extension Cohort A

EXPERIMENTAL

IMA203 at RP2D

Biological: IMA203 Product; Device: IMADetect®

Extension Cohort B (closed to enrollment)

EXPERIMENTAL

IMA203 at RP2D + nivolumab

Biological: IMA203 Product; Drug: Nivolumab

Extension Cohort AA

EXPERIMENTAL

IMA203 at final RP2D (flat dose)

Biological: IMA203 product- flat dose; Device: IMADetect®

Uveal Melanoma

EXPERIMENTAL

IMA203 at RP2D

Biological: IMA203 Product; Device: IMADetect®

Dose Escalation B

EXPERIMENTAL

Dose escalation of IMA203CD8

Biological: IMA203CD8 Product; Device: IMADetect®

Extension Cohort C

EXPERIMENTAL

IMA203CD8 at dose levels confirmed to be safe

Biological: IMA203CD8 Product; Device: IMADetect®

Extension Cohort D

EXPERIMENTAL

IMA203CD8 at dose levels confirmed to be safe; without IL-2

Biological: IMA203CD8 Product; Device: IMADetect®

Ovarian

EXPERIMENTAL

IMA203CD8 monotherapy at dose levels confirmed to be safe

Biological: IMA203CD8 Product; Device: IMADetect®

Endometrial

EXPERIMENTAL

IMA203CD8 monotherapy at dose levels confirmed to be safe

Biological: IMA203CD8 Product; Device: IMADetect®

Head and Neck, Lung, and Triple Negative Breast Cancer

EXPERIMENTAL

IMA203CD8 monotherapy at dose levels confirmed to be safe

Biological: IMA203CD8 Product; Device: IMADetect®

Rare Cancers

EXPERIMENTAL

IMA203CD8 monotherapy at dose levels confirmed to be safe

Biological: IMA203CD8 Product; Device: IMADetect®

Interventions

IMA203 product- flat dose BIOLOGICAL

The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells

Also known as: anzutresgene autoleucel, anzu-cel

Extension Cohort AA

IMA203CD8 Product BIOLOGICAL

The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula

Dose Escalation B; Endometrial; Extension Cohort C; Extension Cohort D; Head and Neck, Lung, and Triple Negative Breast Cancer; Ovarian; Rare Cancers

IMADetect® DEVICE

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.

Dose Escalation A (closed to enrollment); Dose Escalation B; Endometrial; Extension Cohort A; Extension Cohort AA; Extension Cohort C; Extension Cohort D; Head and Neck, Lung, and Triple Negative Breast Cancer; Ovarian; Rare Cancers; Uveal Melanoma

IMA203 Product BIOLOGICAL

The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula

Also known as: anzutresgene autoleucel, anzu-cel

Dose Escalation A (closed to enrollment); Extension Cohort A; Extension Cohort B (closed to enrollment); Uveal Melanoma

Nivolumab DRUG

Nivolumab will be given post IMA203/IMA203CD8 infusion, after hematologic recovery is achieved. Clinical supply provided by Bristol Myers Squibb.

Also known as: Opdivo®

Extension Cohort B (closed to enrollment)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.).

Sponsors & Collaborators

• Immatics US, Inc.: lead

Study Sites (21)

Stanford Cancer Institute

Stanford, California, 94305, United States

RECRUITING

University of Colorado, Anschutz Medical Campus

Aurora, Colorado, 80045, United States

ACTIVE NOT RECRUITING

University of Miami Hospital and Clinics

Miami, Florida, 33136, United States

RECRUITING

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

ACTIVE NOT RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

ACTIVE NOT RECRUITING

Ohio State University Wexner Medical Center Gynecologic Oncology at Mill Run

Columbus, Ohio, 43026, United States

RECRUITING

University of Pennsylvania, Perelamn Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Thomas Jefferson University, Honickman Center

Philadelphia, Pennsylvania, 19107, United States

ACTIVE NOT RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

ACTIVE NOT RECRUITING

Universitätsklinikum Heidelberg, Nationales Centrum für Tumorerkrankungen (NCT)

Heidelberg, Baden-Wurttemberg, 69120, Germany

RECRUITING

Klinikum rechts der Isar der Technischen Universität München

Munich, Bavaria, 81675, Germany

RECRUITING

Universitätsklinikum Würzburg

Würzburg, Bavaria, 97080, Germany

RECRUITING

Universitätsklinikum Bonn - Medizinische Klinik III

Bonn, North Rhine-Westphalia, 53127, Germany

RECRUITING

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, Rhineland-Palatinate, 55131, Germany

RECRUITING

Universitätsklinikum C.-G.-Carus Dresden

Dresden, Saxony, 01307, Germany

RECRUITING

Charité Benjamin Franklin - Klinik für Hämatologie und Onkologie

Berlin, 12203, Germany

RECRUITING

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

RECRUITING

Related Publications (1)

• Wermke M, Araujo DM, Chatterjee M, Tsimberidou AM, Holderried TAW, Jazaeri AA, Reshef R, Bokemeyer C, Alsdorf W, Wetzko K, Brossart P, Aslan K, Backert L, Bunk S, Fritsche J, Gulde S, Hengler S, Hilf N, Hossain MB, Hukelmann J, Kalra M, Krishna D, Kursunel MA, Maurer D, Mayer-Mokler A, Mendrzyk R, Mohamed A, Pozo K, Satelli A, Letizia M, Schuster H, Schoor O, Wagner C, Rammensee HG, Reinhardt C, Singh-Jasuja H, Walter S, Weinschenk T, Luke JJ, Britten CM. Autologous T cell therapy for PRAME+ advanced solid tumors in HLA-A*02+ patients: a phase 1 trial. Nat Med. 2025 Jul;31(7):2365-2374. doi: 10.1038/s41591-025-03650-6. Epub 2025 Apr 9.

  PMID: 40205198 DERIVED

MeSH Terms

Conditions

Neoplasms; Recurrence; Melanoma; Uveal Melanoma; Ovarian Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Cedrik Britten, M.D.

  Immatics US, Inc.

  STUDY DIRECTOR

Central Study Contacts

Immatics US, Inc.

CONTACT

+1 346 204-5400; ctgovinquiries@immatics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2018
• First Posted: September 26, 2018
• Study Start: May 14, 2019
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): June 1, 2032
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

DE (8); US (13)