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

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).

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Publication Details

Journal
Cell Reports Medicine
Published
2025-03-06
DOI
https://doi.org/10.1016/j.xcrm.2025.101994
Citations
4
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
4.18

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article

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

Marcus O. Butler, Fiona Thistlethwaite, Ramakrishna Edukulla, Jason Wustner et al.
4 citations
Cell Reports Medicine
CAR-T cell therapy research
4.18
article

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

Marcus O. Butler, Fiona Thistlethwaite, Ramakrishna Edukulla, Jason Wustner, Melissa L. Johnson, Takami Sato, Juanita Suzanne Lopez, Sandra P. D’Angelo, Mohammed Milhem, Brian Andrew Van Tine, Hendrik‐Tobias Arkenau, Jordi Rodon, Shannon Marshall
article en
4 citations

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).

Cell Reports MedicineVol. 6(4)
Memorial Sloan Kettering Cancer Center (US), The University of Texas MD Anderson Cancer Center (US), Institute of Cancer Research (GB), Sarah Cannon Research Institute (GB), University of Toronto (CA), Washington University in St. Louis (US), Cornell University (US), University of Iowa Hospitals and Clinics (US), Princess Margaret Cancer Centre (CA), University of Manchester (GB), Immunocore (United States) (US), Sarah Cannon (US), Sidney Kimmel Cancer Center (US), Royal Marsden Hospital (GB), The Christie NHS Foundation Trust (GB), Tennessee Oncology (US), Sidney Kimmel Comprehensive Cancer Center (US), University College London (GB)
HCA Healthcare
Good health and well-being
Openalex Percentile: Top 6%
CAR-T cell therapy research
4.18
DOIOpen Access PDFOpenAlex
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