Abstract 4935
Background
ImmTAC® 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 design
IMCnyeso-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 identification
NCT03515551.
Editorial acknowledgement
Legal entity responsible for the study
Immunocore.
Funding
Immunocore.
Disclosure
J. 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.
Resources from the same session
5007 - Functional systemic CD4 immunity is required for clinical responses to PD-L1/PD-1 blockade therapy
Presenter: Miren Zuazo
Session: Poster Display session 3
Resources:
Abstract
5760 - Landscape of PD-L1 expression status in Chinese solid tumor patients.
Presenter: Yi Zhong
Session: Poster Display session 3
Resources:
Abstract
3733 - Anti-cancer and immunomodulatory effects of cobimetinib in triple negative breast cancer
Presenter: Chun-Yu Liu
Session: Poster Display session 3
Resources:
Abstract
4426 - Differential expression of immunoregulatory molecules and highly-associated cancer genes may provide novel insights into strategic trial design for therapeutics
Presenter: Jacob Adashek
Session: Poster Display session 3
Resources:
Abstract
2752 - Insights into the Tumor Immune Microenvironment using Tissue Phenomics to Drive Cancer Immunotherapy
Presenter: Martin Groher
Session: Poster Display session 3
Resources:
Abstract
5713 - Immune competent somatic mosaic model of colorectal cancer
Presenter: Stefania Napolitano
Session: Poster Display session 3
Resources:
Abstract
1898 - Genomic correlates of response to anti-PDL1 Atezolizumab in non-small-cell lung cancer OAK and POPLAR trials
Presenter: Hari Singhal
Session: Poster Display session 3
Resources:
Abstract
3246 - Erdafitinib (erda) versus available therapies in advanced urothelial cancer: A matching adjusted indirect comparison
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
3311 - High level of activity of Nivolumab anti-PD-1 immunotherapy and favorable outcome in metastatic/refractory MSI-H non-colorectal cancer: Results of the MSI cohort from the French AcSé program
Presenter: Christophe Tournigand
Session: Poster Display session 3
Resources:
Abstract
2314 - TP53 and ATM Co-mutation Predicts Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer
Presenter: Yu Chen
Session: Poster Display session 3
Resources:
Abstract