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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 Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 26
Issue 13
Date 2020 Jul 01
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
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, and may resulting in inhibition of tumor growth, T cell infiltration and increased killing of tumor cells (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
Unknown unknown lung non-small cell carcinoma not applicable OMTX705 + Paclitaxel Preclinical - Pdx Actionable In a preclinical study, OMTX705 treatment in combination with Taxol (paclitaxel) enhanced tumor growth inhibition in a patient-derived xenograft (PDX) model of non-small cell lung cancer (PMID: 32161121). 32161121
Unknown unknown ovarian cancer not applicable OMTX705 Preclinical - Pdx Actionable In a preclinical study, OMTX705 treatment inhibited tumor growth in a patient-derived xenograft (PDX) model of ovarian cancer (PMID: 32161121). 32161121
Unknown unknown triple-receptor negative breast cancer not applicable OMTX705 Preclinical - Pdx Actionable In a preclinical study, OMTX705 treatment inhibited tumor growth in a patient-derived xenograft (PDX) model of triple-negative breast cancer (PMID: 32161121). 32161121
Unknown unknown pancreatic cancer not applicable Gemcitabine + OMTX705 Preclinical - Pdx Actionable In a preclinical study, OMTX705 treatment in combination with Gemzar (gemcitabine) inhibited tumor growth and induced durable regression in a patient-derived xenograft (PDX) model of pancreatic cancer (PMID: 32161121). 32161121
Unknown unknown lung non-small cell carcinoma not applicable OMTX705 Preclinical - Pdx Actionable In a preclinical study, OMTX705 treatment inhibited tumor growth in a patient-derived xenograft (PDX) model of non-small cell lung cancer (PMID: 32161121). 32161121
Unknown unknown pancreatic cancer not applicable OMTX705 Preclinical - Pdx Actionable In a preclinical study, OMTX705 treatment induced apoptosis, reduced proliferation, and led to tumor growth inhibition and regression in a patient-derived xenograft (PDX) model of pancreatic cancer (PMID: 32161121). 32161121