Abstract A35: Biomarker Strategy To Guide Clinical Development Of ImmTAC™ molecules , A Novel Class Of Bispecific T Cell Engaging Biologic Drugs

Abstract

IMCgp100, a first in class immunotherapy, is a T cell redirecting bispecific biologic comprising an affinity enhanced T-cell receptor specific for gp100 and an anti-CD3 scFV. Phase I/IIa data supported a favourable safety profile and durable responses in cutaneous and uveal melanoma (CM and UM) were observed. To complement the clinical studies we have developed a comprehensive biomarker strategy, which includes analysis of markers in both the tumour and periphery, to aid our understanding of pharmacodynamics, patient response and potential mechanisms of resistance. The data obtained provide evidence of the pharmacodynamic effects of chemokine/cytokine release, in both the tumor and periphery, and lymphocyte infiltration into tumors over 2 days post dose. Changes in the levels of certain chemokines following the first dose of IMCgp100 were associated with tumor shrinkage. In addition, biological differences in marker responses were also seen between CM and UM patients. The biomarker strategy developed forms the basis for the on-going Ph II development of IMCgp100 in CM and UM and for other ImmTAC molecules, both as single agents and in combination, for the treatment of solid tumours. Citation Format: Cheryl McAlpine, Sandra Herrero Gonzalez, Lindsay Bawden, David Krige, William Shingler, Andy Johnson, Sanjay Patel, Debbie Parker, Christina M. Coughlin, Namir J. Hassan, Bent K. Jakobsen. Biomarker Strategy To Guide Clinical Development Of ImmTAC™ molecules , A Novel Class Of Bispecific T Cell Engaging Biologic Drugs. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A35.