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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 (+5 others)
2020 Clinical Cancer Research  

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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. 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
more » ... mouse models alone and in combination with chemotherapy as well as immunotherapy in PD1-resistant tumors. 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. 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.
doi:10.1158/1078-0432.ccr-19-2238 pmid:32161121 fatcat:iylthvzrfbc5nm5ihi5ikj5sle
Citation

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. "OMTX705, a Novel FAP-Targeting ADC demonstrates Activity in Chemotherapy and PD1-Resistant Solid Tumors Models." Clinical Cancer Research 26.13 (2020) clincanres.2238.2019