March 13, 2020

Joint research paper on FAP-targeting ADC published in Clinical Cancer Research

OMTX705, a Novel FAP-Targeting ADC Demonstrates Activity in Chemotherapy and PD1-Resistant Solid Tumors Models

Myriam Fabre, Cristina Ferrer, Saioa Dominguez-Hormaetxe, Bruno Bockorny, Laura Murias, Oliver Seifert, Stephan A Eisler, Roland E Kontermann, Klaus Pfizenmaier, So Young Lee, Maria dM Vivanco, Pedro P Lopez-Casas, Sofia Perea, Muhammad Abbas, Wolfgang Richter, Laureano Simón, Manuel Hidalgo

Abstract

Purpose: The tumor microenvironment plays a key role in cancer development and progression and is involved in resistance to chemo- and immunotherapy. Cancer-associated fibroblast expressing fibroblast activating protein α (FAPα) is one of the predominant stroma cell types and are involved in resistance to immunotherapy.

Experimental design: We generated OMTX705, a novel antibody-drug conjugate from a humanized anti-FAP antibody linked to a new cytolysin. Here we studied its antineoplastic activity in vitro and in preclinical mouse models alone and in combination with chemotherapy as well as immunotherapy in PD1-resistant tumors.

Results: In Avatar models, OMTX705 showed a 100% tumor growth inhibition and prolonged tumor regressions as single agent and in combination with chemotherapy. Treatment re-challenge following treatment discontinuation induced additional tumor regression suggesting lack of treatment resistance. In a mouse model with a humanized immune system resistant to PD-1 inhibition, OMTX705 increased tumor infiltration by CD8+ T cells, induced complete regressions, and delayed tumor recurrence.

Conclusions: These data suggest that FAP-targeting with OMTX705 represents a novel and potent strategy for cancer treatment including tumors resistant to immunotherapy and support its clinical development.

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