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RecruitingInterventionalPhase 1/Phase 2

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

NCT ID: NCT03686124Sponsor: Immatics US, Inc.Last updated: 2026-05-13

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).

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.

Arms & interventions

  • BiologicalIMA203 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

  • BiologicalIMA203 product- flat dose

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

  • BiologicalIMA203CD8 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

  • DrugNivolumab

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

  • DeviceIMADetect®

    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.

Outcome measures

Primary

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

    Number of patients with dose-limiting toxicities (DLTs)

    Time frame: 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).

    Time frame: 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

    Time frame: 5 years

Secondary

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

    Time frame: up to 5 years post treatment

  • Phase 1 and 2: Tumor response

    Time frame: up to 5 years

  • Phase 2: Patient reported quality of life

    Time frame: up to 5 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy 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-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 locations (13)

Stanford Cancer Institute

Stanford, California, 94305

Recruiting
Allison Warner, MD · Contact

University of Colorado, Anschutz Medical Campus

Aurora, Colorado, 80045

Recruiting
Sapna Patel, MD · Contact

University of Miami Hospital and Clinics

Miami, Florida, 33136

Recruiting

University of Chicago Medical Center

Chicago, Illinois, 60637

Recruiting
Katherine Kurnit, MD · Contact

Massachusetts General Hospital

Boston, Massachusetts, 02114

Recruiting
Oldadapo O. Yeku, MD. PhD · Contact

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Recruiting
Alexander Shoushtari, MD · Contact

Ohio State University Wexner Medical Center Gynecologic Oncology at Mill Run

Columbus, Ohio, 43026

Recruiting
Casey Cosgrove, MD · Contact

University of Pennsylvania, Perelamn Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104

Recruiting
Janos Tanyi, MD, PhD · Contact

Thomas Jefferson University, Honickman Center

Philadelphia, Pennsylvania, 19107

Recruiting
Rino Seedor, MD · Contact

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111

Recruiting
Anthony Olszanski, MD, RPh · Contact
Anthony Olszanski, MD · Principal Investigator

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232

Recruiting
Diwakar Davar, M.D. · Contact
Jason Luke, M.D. · Principal Investigator

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting
Dejka M Araujo, M.D. · Contact
Dejka M Araujo, M.D. · Principal Investigator

Fred Hutchinson Cancer Center

Seattle, Washington, 98109

Recruiting
Sylvia Lee, MD · Contact

References

  • 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.(PubMed)