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
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
Study locations (13)
Stanford Cancer Institute
Stanford, California, 94305
University of Colorado, Anschutz Medical Campus
Aurora, Colorado, 80045
University of Miami Hospital and Clinics
Miami, Florida, 33136
University of Chicago Medical Center
Chicago, Illinois, 60637
Massachusetts General Hospital
Boston, Massachusetts, 02114
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Ohio State University Wexner Medical Center Gynecologic Oncology at Mill Run
Columbus, Ohio, 43026
University of Pennsylvania, Perelamn Center for Advanced Medicine
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University, Honickman Center
Philadelphia, Pennsylvania, 19107
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
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)