Journal article
Phase 1 study of IMCnyeso, a T cell receptor bispecific ImmTAC targeting NY-ESO-1-expressing malignancies
Cell reports. Medicine, Vol.6(4), 101994
04/2025
DOI: 10.1016/j.xcrm.2025.101994
PMCID: PMC12047507
PMID: 40054461
Abstract
SummaryIMCnyeso, 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).
Details
- Title: Subtitle
- Phase 1 study of IMCnyeso, a T cell receptor bispecific ImmTAC targeting NY-ESO-1-expressing malignancies
- Creators
- Juanita S Lopez - Institute of Cancer ResearchMohammed Milhem - University of IowaMarcus O Butler - Princess Margaret Cancer CentreFiona Thistlethwaite - The Christie NHS Foundation TrustBrian A Van Tine - Washington University in St. LouisSandra P D’Angelo - Memorial Sloan Kettering Cancer CenterMelissa L Johnson - Tennessee OncologyTakami Sato - Sidney Kimmel Cancer CenterHendrik-Tobias Arkenau - University College LondonRamakrishna Edukulla - ImmunocoreJason WustnerShannon Marshall - ImmunocoreJordi Rodon - The University of Texas MD Anderson Cancer Center
- Resource Type
- Journal article
- Publication Details
- Cell reports. Medicine, Vol.6(4), 101994
- DOI
- 10.1016/j.xcrm.2025.101994
- PMID
- 40054461
- PMCID
- PMC12047507
- NLM abbreviation
- Cell Rep Med
- ISSN
- 2666-3791
- eISSN
- 2666-3791
- Publisher
- CELL PRESS
- Number of pages
- 1
- Grant note
- Immunocore Ltd.
The authors would like to thank all participating patients, their families, investigators and sub-investigators, and staff at the study sites. This study was funded by Immunocore Ltd.
- Language
- English
- Electronic publication date
- 2025
- Date published
- 04/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984798362202771
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