1309TiP - Trial in progress: First-in-human study of a novel anti-NY-ESO-1–anti-CD3, TCR-based bispecific (IMCnyeso) as monotherapy in NY-ESO-1/LAGE-1A-positive advanced solid tumours (IMCnyeso-101)

Abstract

BackgroundImmTAC® bispecific molecules are unique TCR–anti-CD3 agents that redirect T cells against intracellular antigens, in contrast to antibody-based therapies, which are limited to extracellular antigens. The most advanced ImmTAC, tebentafusp (IMCgp100), against melanocyte-associated lineage antigen gp100, has shown monotherapy responses in advanced melanoma, a solid tumor. In contrast, bispecific antibodies have shown activity in hematologic cancers but appear less active in solid tumors. ImmTAC molecules recognize a specific peptide presented on a defined Class I HLA molecule via an affinity enhanced, engineered, soluble TCR. Through the addition of an anti-CD3 scFv domain fused to the TCR targeting domain, an ImmTAC can redirect T cell activity against cancer cells, regardless of the specificity of the T cell. IMCnyeso is an ImmTAC against NY-ESO-1/LAGE-1A, which are cancer testis antigens expressed in a variety of solid malignancies, but with very low or absent normal tissue expression. Trial designIMCnyeso-101 is a multi-center, open-label, first-in-human study of IMCnyeso in HLA-A*02:01-positive patients with NY-ESO-1- and/or LAGE-1A-positive advanced NSCLC, synovial sarcoma, melanoma, or urothelial carcinoma. The study includes dose escalation (Bayesian logistic regression models) and expansion for IMCnyeso monotherapy (QW), followed by expansion into indication specific arms to test for signs of efficacy in defined patient cohorts. Primary endpoints are establishing MTD/RP2D and safety and tolerability. Secondary endpoints include: characterization of PK and ADA, efficacy by RECIST v1.1 (PFS, ORR and DOR) and OS. The dose escalation portion of the study is in progress. The trial continues to enroll; NCT number NCT03515551. Clinical trial identificationNCT03515551. Legal entity responsible for the studyImmunocore. FundingImmunocore. DisclosureJ. Lopez: Research grant / Funding (institution), During the conduct of the study: Immunocore, Roche, Genentech; Advisory / Consultancy, Outside the submitted work: Novartis (personal fees); Research grant / Funding (institution), Outside the submitted work: MSD; Research grant / Funding (institution), Outside the submitted work (grant and non-financial support): Basilea; Advisory / Consultancy, Research grant / Funding (institution), Outside the submitted work: Genmab. T. Sato: Advisory / Consultancy: Immunocore; Advisory / Consultancy: IDEAYA Biosciences; Advisory / Consultancy: Neon Therapeutics, Inc. F. Thistlethwaite: Honoraria (self), Achilles Therapeutics. B. Van Tine: Honoraria (institution), Advisory / Consultancy: Immunocore ; Advisory / Consultancy: Epizyme; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy: CytRX; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Speaker Bureau / Expert testimony: Caris; Advisory / Consultancy: Immune Design; Advisory / Consultancy: Daiichi Sankyo; Speaker Bureau / Expert testimony: Adaptimmune; Advisory / Consultancy: Plexxicon; Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Research grant / Funding (self): Merck; Research grant / Funding (self): Tracon. J.A. Rodon: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Orion Pharmaceuticals; Advisory / Consultancy: Servier Pharma; Honoraria (self), Advisory / Consultancy: Peptomyc; Honoraria (self): Merck Sharp; Advisory / Consultancy: Merck Sharp & Dome; Advisory / Consultancy: Kelun Pharma/Klus Pharma; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Roche Pharma; Advisory / Consultancy: Elipses Pharma; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Spectrum Pharmaceuticals; Research grant / Funding (institution): Tocagen; Research grant / Funding (institution): Symphogen; Research grant / Funding (institution): BioAtla; Research grant / Funding (institution): GenMab; Research grant / Funding (institution): CytomX; Research grant / Funding (institution): Kelun-Biotech; Research grant / Funding (institution): Takeda-Millenium; Research grant / Funding (institution): Glaxosmithkline; Research grant / Funding (institution): Ipsen. J. Dukes: Shareholder / Stockholder / Stock options, Full / Part-time employment: Immunocore Ltd. R. Easton: Shareholder / Stockholder / Stock options, Full / Part-time employment: Immunocore. S. Marshall: Shareholder / Stockholder / Stock options, Full / Part-time employment: Immunocore. All other authors have declared no conflicts of interest.