First-in-Human Study of MDG1011, a TCR-T Therapy Directed Against HLA-A*02:01-Restricted PRAME Antigen for High-Risk Myeloid and Lymphoid Neoplasms

Thomas S, Wermke M, Vučinić V, Wagner-Drouet E, Mackensen A, Zeiser R, Bug G, Schmitt M, Herr W, Prinz PU, Bürdek M, Raffegerst S, Tafuri A, Geiger C, Crame K, Goedkoop R, Pinkernell K, Schendel DJ (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Cancers MDPI

Book Volume: 17

Article Number: 2968

Journal Issue: 18

DOI: 10.3390/cancers17182968

Abstract

Background/objectives: MDG1011 is a Preferentially Expressed Antigen in Melanoma (PRAME)-specific autologous T cell receptor (TCR) T cell therapy for HLA-A*02:01-positive patients. Data from the first-in-human (FIH) clinical trial, CD-TCR-001, are reported here regarding treatment feasibility, safety, tolerability, and clinical activity of MDG1011 in patients with relapsed/refractory (r/r) acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). Methods: Nine of thirteen enrolled patients received MDG1011 at dose levels ranging from 0.1 to 5 × 106 TCR-T cells per kg body weight. In addition to clinical assessments, immune monitoring of cytokines associated with cytokine release syndrome (CRS), presence and persistence of MDG1011, and changes in levels of PRAME mRNA were used to assess safety and potential biological activity at defined time points. Results: The treatment was well tolerated. No dose-limiting toxicities (DLTs) were observed, and the most common serious adverse events were associated with lymphodepleting chemotherapy and/or disease progression. Various parameters, such as measurable clinical responses in two patients, the occurrence of CRS in two additional patients, and reductions in PRAME mRNA levels in bone marrow (BM) or peripheral blood (PB) in seven patients, served as signs of the clinical and biological activity of MDG1011 TCR-T therapy. Conclusions: Patients enrolled in the phase 1 part of CD-TCR-001 displayed signs of potential clinical and biological activity of MDG1011 among the small number of patients studied. Advanced disease stage and rapid progression in the r/r AML patients limited clinical impact. The acceptable safety profile of MDG1011 merits further investigation of this TCR-T therapy, potentially in patients at an earlier stage of their disease and with lower tumor burden.

Involved external institutions

Medigene AG DE Germany (DE) Universitätsklinikum Regensburg DE Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE) Universitätsklinikum Leipzig DE Germany (DE) Universitätsmedizin der Johannes Gutenberg-Universität Mainz DE Germany (DE) Bayerisches Zentrum für Krebsforschung (BZKF) DE Germany (DE) Universitätsklinikum Freiburg DE Germany (DE) Universitätsklinikum Frankfurt am Main (KGU) DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE)

How to cite

APA:

Thomas, S., Wermke, M., Vučinić, V., Wagner-Drouet, E., Mackensen, A., Zeiser, R.,... Schendel, D.J. (2025). First-in-Human Study of MDG1011, a TCR-T Therapy Directed Against HLA-A*02:01-Restricted PRAME Antigen for High-Risk Myeloid and Lymphoid Neoplasms. Cancers, 17(18). https://doi.org/10.3390/cancers17182968

MLA:

Thomas, Simone, et al. "First-in-Human Study of MDG1011, a TCR-T Therapy Directed Against HLA-A*02:01-Restricted PRAME Antigen for High-Risk Myeloid and Lymphoid Neoplasms." Cancers 17.18 (2025).

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