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Ref Type Journal Article
PMID (32161121)
Authors Fabre M, Ferrer C, Domínguez-Hormaetxe S, Bockorny B, Murias L, Seifert O, Eisler SA, Kontermann RE, Pfizenmaier K, Lee SY, Vivanco MD, López-Casas PP, Perea S, Abbas M, Richter W, Simon L, Hidalgo M
Title OMTX705, a Novel FAP-Targeting ADC Demonstrates Activity in Chemotherapy and Pembrolizumab-Resistant Solid Tumor Models.
Journal Vol Issue Date Pages Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research 26 13 2020 Jul 01 3420-3430 Clin Cancer Res
URL
Abstract Text 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 is 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 preclinical mouse models alone and in combination with chemotherapy as well as immunotherapy in PD-1-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 rechallenge 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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
OMTX705 OMTX705 0 1
Drug Name Trade Name Synonyms Drug Classes Drug Description
OMTX705 OMTX 705|OMTX-705 OMTX705 is an antibody-drug conjugate that targets fibroblast-activating protein alpha (FAP-alpha), potentially resulting in increased killing of tumor cells, T cell infiltration, and inhibition of tumor growth (PMID: 32161121).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References