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Description
Onartuzumab is a monoclonal antibody that blocks the binding of HGF to the MET receptor.
Uses
Onartuzumab (MetMAb) is a unique, humanized and affinity-matured monovalent (one-armed) monoclonal antibody against the MET receptor. Onartuzumab potently inhibits HGF binding and receptor phosphorylation and signaling. Onartuzumab has antibody-like pharmacokinetics and antitumor activity[1].
Clinical Use
Onartuzumab is ineffective in improving clinical outcomes in (i) combination with current first-line chemotherapy in advanced nonsquamous cell NSCLC , (ii) combination with erlotinib in previously treated stage IIIB or IV NSCLC patients (Phase III) , and (iii) combination with platinum-doublet chemotherapy in advanced squamous cell NSCLC (Phase II) .
in vivo
Onartuzumab (30 mg/kg, IP, twice a week for 2 mouth) suppresses tumor growth[3].
Animal Model: | Human HGF-transgenic SCID mice implanted with BxPC3 tumor cells, nude (nu/nu) mice implanted with KP4 human pancreatic xenograft tumor cells[3] |
Dosage: | 30 mg/kg |
Administration: | IP, twice a week for 2 mouth |
Result: | Suppressed tumor growth, but did not affect the mean in vivo human HGF levels. |
Animal Model: | U-87 MG tumor-bearing mice[3] |
Dosage: | 30 mg/kg |
Administration: | IP, once |
Result: | Resulted in profound TGI (tumor growth inhibition) with 4/10 mice demonstrating a partial response (>50% reduction in tumor size) and 6/10 mice demonstrating a complete response (100% tumor regression). |
References
[1] Merchant M, et al. Monovalent antibody design and mechanism of action of onartuzumab, a MET antagonist with anti-tumor activity as a therapeutic agent. Proc Natl Acad Sci U S A. 2013 Aug 6;110(32):E2987-96. DOI:10.1073/pnas.1302725110
[2] Prell RA, et al. Placental and Fetal Effects of Onartuzumab, a Met/HGF Signaling Antagonist, When Administered to Pregnant Cynomolgus Monkeys. Toxicol Sci. 2018 Sep 1;165(1):186-197. DOI:10.1093/toxsci/kfy141
[2] Prell RA, et al. Placental and Fetal Effects of Onartuzumab, a Met/HGF Signaling Antagonist, When Administered to Pregnant Cynomolgus Monkeys. Toxicol Sci. 2018 Sep 1;165(1):186-197. DOI:10.1093/toxsci/kfy141
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