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Ref Type Journal Article
PMID (31338636)
Authors Davis SL, Cardin DB, Shahda S, Lenz HJ, Dotan E, O'Neil BH, Kapoun AM, Stagg RJ, Berlin J, Messersmith WA, Cohen SJ
Title A phase 1b dose escalation study of Wnt pathway inhibitor vantictumab in combination with nab-paclitaxel and gemcitabine in patients with previously untreated metastatic pancreatic cancer.
Journal Vol Issue Date Pages Journal Short Title
Investigational new drugs 38 3 2020 Jun 821-830 Invest New Drugs
URL
Abstract Text Vantictumab is a fully human monoclonal antibody that inhibits Wnt pathway signaling through binding FZD1, 2, 5, 7, and 8 receptors. This phase Ib study evaluated vantictumab in combination with nab-paclitaxel and gemcitabine in patients with untreated metastatic pancreatic adenocarcinoma. Patients received vantictumab at escalating doses in combination with standard dosing of nab-paclitaxel and gemcitabine according to a 3 + 3 design. A total of 31 patients were treated in 5 dosing cohorts. Fragility fractures attributed to vantictumab occurred in 2 patients in Cohort 2 (7 mg/kg every 2 weeks), and this maximum administered dose (MAD) on study was considered unsafe. The dosing schedule was revised to every 4 weeks for Cohorts 3 through 5, with additional bone safety parameters added. Sequential dosing of vantictumab followed by nab-paclitaxel and gemcitabine was also explored. No fragility fractures attributed to vantictumab occurred in these cohorts; pathologic fracture not attributed to vantictumab was documented in 2 patients. The study was ultimately terminated due to concerns around bone-related safety, and thus the maximum tolerated dose (MTD) of the combination was not determined. The MAD of vantictumab according to the revised dosing schedule was 5 mg/kg (n = 16).

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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
Vantictumab Vantictumab 1 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
Vantictumab anti-Fzd7|OMP-18R5 WNT Inhibitor 15 Vantictumab (OMP-18R5) is a monoclonal antibody that targets Frizzled receptors 1, 2, 5, 7, and 8, resulting in decreased Wnt signaling and potentially leading to decreased tumor growth (PMID: 22753465, PMID: 31338636).
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