Phase 1 study of IMCnyeso, a T cell receptor bispecific ImmTAC targeting NY-ESO-1-expressing malignancies Journal Article
| 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. |
| Article Title: | Phase 1 study of IMCnyeso, a T cell receptor bispecific ImmTAC targeting NY-ESO-1-expressing malignancies |
| 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). © 2025 Immunocore |
| Keywords: | adult; aged; middle aged; overall survival; hypophosphatemia; flow cytometry; follow up; cd8+ t lymphocyte; t lymphocyte; interleukin 2; cancer immunotherapy; melanoma; progression free survival; phase 2 clinical trial; interleukin 10; interleukin 8; antineoplastic activity; ifosfamide; drug dose escalation; febrile neutropenia; fever; hypoxia; hypotension; liver failure; lung metastasis; t lymphocyte receptor; immunotherapy; multicenter study; immunogenicity; pazopanib; interleukin 6; headache; maximum tolerated dose; phase 1 clinical trial; kaplan meier method; synovial sarcoma; corticosteroid; anthracycline; uvea melanoma; hla a antigen; transitional cell carcinoma; pharmacokinetics; solid tumors; tumor necrosis factor; sinus tachycardia; non small cell lung cancer; tumor microenvironment; cancer-testis antigen; t cell receptor; cytokine release syndrome; dose escalation; tocilizumab; human; male; female; article; bispecific; malignant neoplasm; immtac; electrochemiluminescence immunoassay; ny-eso |
| Journal Title: | Cell Reports Medicine |
| Volume: | 6 |
| Issue: | 4 |
| ISSN: | 2666-3791 |
| Publisher: | Cell Press |
| Date Published: | 2025-04-15 |
| Start Page: | 101994 |
| Language: | English |
| DOI: | 10.1016/j.xcrm.2025.101994 |
| PUBMED: | 40054461 |
| PROVIDER: | scopus |
| PMCID: | PMC12047507 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
