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    Phase I dose escalation of IMC-C103C, a CD33MAGE-A4 T-cell receptor (TCR) bispecific protein

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    Authors
    Davar, D.
    Sweis, R. F.
    Blumenschein, G.
    Gutierrez, R.
    Melero, I.
    Chen, H. A.
    Thistlethwaite, F.
    Moore, K. N.
    Segal, N. H.
    Garralda, E.
    Wilky, B.
    Arkenau, H. T.
    Evans, T. R. J.
    Johnson, M. L.
    Dar, M.
    Holland, C.
    Marshall, S.
    Stanhope, S.
    Kirk, P.
    Lopez, J. S.
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    Affiliation
    UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    Issue Date
    2021
    
    Metadata
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    Abstract
    Background: TCR bispecific proteins (bsp) redirect polyclonal T cells to target intra/ extracellular proteins in cancer, as validated by tebentafusp (CD3gp100 TCR) with a survival benefit in metastatic uveal melanoma (HR 0.51). IMC-C103C is a TCR bsp against MAGE-A4, a cancer-testis antigen expressed in several tumor types (eg, lung, ovarian, HNSCC, GEJ) but minimally in normal tissue. Methods: HLA-A*02:01+ pts with selected advanced tumors are eligible; prospective MAGE-A4 testing is required in indications with lower MAGE-A4 prevalence. The Ph1 primary objective is to identify the expansion dose. Other objectives: adverse events (AE), clinical activity (RECIST v1.1), biomarkers. IMC-C103C is dosed IV weekly, with step-dosing at > 15 mg (full dose at Day 15). Results: As of 20 Aug 2021, 42 pts were treated in 9 cohorts. 18 pts (78% 3L+ ovarian) were treated at 90 mg, doses consistently showing robust evidence of T cell activity (Table). Median MAGE-A4 H-score was low, 19. Paired tumor biopsies (n¼6) showed substantial increases in CD3, CD8 T cell infiltration on treatment. Most common related AEs (n¼42) were pyrexia 50%, chills 50%, cytokine release syndrome 36%, headache 31%, and nausea 31%. These were typically Gr1/2, occurred in first 3 weeks and rapidly resolved. Reversible neutropenia (19%), the most common Gr3 related AE, typically occurred at 90 mg. No related AE led to discontinuation or death. Clinical activity is seen in platinum-resistant ovarian cancer: 2 confirmed PRs (15 mg, duration 8.3mo; 90 mg, response ongoing); 2 pts at 140 mg had overall reduction in target lesions (-44%, -81%) but had new lesions; all 4 pts had MAGE-A4 H-score
    Citation
    Davar D, Sweis RF, Blumenschein G, Gutierrez R, Melero I, Chen HA, et al. Phase I dose escalation of IMC-C103C, a CD33MAGE-A4 T-cell receptor (TCR) bispecific protein. Annals of Oncology. 2021;32:S1411-S3.
    Journal
    Annals of Oncology
    URI
    http://hdl.handle.net/10541/624995
    DOI
    10.1016/j.annonc.2021.10.109
    Additional Links
    https://dx.doi.org/10.1016/j.annonc.2021.10.109
    Type
    Meetings and Proceedings
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.annonc.2021.10.109
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