Thumbnail Image
Item

Phase 1 study of IMCnyeso, a T cell receptor bispecific ImmTAC targeting NY-ESO-1-expressing malignancies

Lopez, J. S.
; 
Milhem, M.
; 
Butler, M. O.
; 
Thistlethwaite, F.
; 
Van Tine, B. A.
; 
D'Angelo, S. P.
; 
Johnson, M. L.
; 
Sato, T.
; 
Arkenau, H. T.
; 
Edukulla, R.
... show 3 more
Citations
Google Scholar:
Lookup
Altmetric:
Abstract
IMCnyeso, an immune mobilizing monoclonal T cell receptor against cancer (ImmTAC) bispecific (New York esophageal squamous cell carcinoma [NY-ESO]×CD3) T cell engager, targets an NY-ESO-1/L-antigen family member-1 isoform A (LAGE-1A) peptide presented by histocompatibility leukocyte antigen (HLA)-A∗02:01. In this phase 1 study, 28 HLA-A∗02:01+ patients with advanced NY-ESO-1/LAGE-1A-positive advanced tumors (n = 28) receive IMCnyeso weekly intravenously (dose range: 3-300 μg; 7 dose-escalation cohorts). The primary objective is to identify the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D); additional objectives include preliminary anti-tumor activity, pharmacokinetics, immunogenicity, and pharmacodynamic changes. The study was terminated before fully enrolling dose escalation, and the MTD was not identified. There are no treatment-related discontinuations or deaths. The most common adverse events are grade 1/2 cytokine release syndrome and associated symptoms. Cytokine induction and transient lymphocyte count decreases are observed at doses 30-300 μg. At these doses, preliminary efficacy includes mixed response (2 patients) and a median overall survival of 12 months. IMCnyeso is well tolerated and, at doses ≥30 μg, induces pharmacodynamic changes consistent with T cell redirection. This study was registered at ClinicalTrials.gov (NCT03515551).
Authors
Lopez, J. S.
Milhem, M.
Butler, M. O.
Thistlethwaite, F.
Van Tine, B. A.
D'Angelo, S. P.
Johnson, M. L.
Sato, T.
Arkenau, H. T.
Edukulla, R.
Wustner, J.
Marshall, S.
Rodon, J.
Affiliation
Drug Development Unit, Institute of Cancer Research and the Royal Marsden Hospital, London SW7 3RP, UK. Electronic address: juanita.lopez@icr.ac.uk. Department of Internal Medicine, Division of Hematology/Oncology and BMT, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto M5G 2M9, ON, Canada; Departments of Medicine and Immunology, University of Toronto, Toronto M5G 2M9, ON, Canada. Division of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M20 4GJ, UK; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK. Division of Oncology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA. Lung Cancer Research Program, Sarah Cannon Research Institute at Tennessee Oncology, Nashville, TN 37203, USA. Department of Medical Oncology, Sidney Kimmel Comprehensive Cancer Center, Jefferson University, Philadelphia, PA 19107, USA. Phase-1 Trials Unit, Sarah Cannon Research Institute, UCL Cancer Institute, University College London, London W1G 6AD, UK. Biometrics, Immunocore, Gaithersburg, MD 20878 USA. Translational Medicine, Immunocore, Conshohocken, PA 19428 USA. Clinical Development, Immunocore, Gaithersburg, MD 20878 USA. Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston 77030, TX, USA.
Description
Date
2025
Publisher
Collections
All Christie Publications
Show all metadata
Files
Thumbnail Image
Found in Unpaywall
Adobe PDF, 2.96 MB
Keywords
Type
Article
Citation
Lopez JS, Milhem M, Butler MO, Thistlethwaite F, Van Tine BA, D'Angelo SP, et al. Phase 1 study of IMCnyeso, a T cell receptor bispecific ImmTAC targeting NY-ESO-1-expressing malignancies. Cell reports Medicine. 2025 Apr 15;6(4):101994. PubMed PMID: 40054461. Pubmed Central PMCID: PMC12047507. Epub 2025/03/09. eng.
Journal Title
Journal ISSN
Volume Title
URI
https://christie.openrepository.com/handle/10541/627981
Embedded videos