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Ref Type Journal Article
PMID (29054986)
Authors Lam ET, Eckhardt SG, Messersmith W, Jimeno A, O'Bryant CL, Ramanathan RK, Weiss GJ, Chadha M, Oey A, Ding HT, Culp PA, Keller SF, Zhao VY, Tsao LC, Singhal A, Holen KD, Von Hoff D
Title Phase I Study of Enavatuzumab, a First-in-Class Humanized Monoclonal Antibody Targeting the TWEAK Receptor, in Patients with Advanced Solid Tumors.
Journal Vol Issue Date Pages Journal Short Title
Molecular cancer therapeutics 17 1 2018 Jan 215-221 Mol Cancer Ther
URL
Abstract Text This phase I study evaluates the safety, MTD, pharmacokinetics (PK), pharmacodynamics, and preliminary anticancer activity of enavatuzumab, a humanized IgG1 antibody to the TWEAK receptor, in patients with advanced solid malignancies. Patients received escalating doses of enavatuzumab given intravenously over 60 minutes every 2 weeks. Blood was obtained for PK and biomarker assessment. Three patients were enrolled per dose level in a standard 3+3 design with response assessment by RECIST version 1.0, every 8 weeks. Thirty patients were enrolled at 6 dose levels ranging from 0.1 to 1.5 mg/kg. Dose-limiting toxicities included grade 4 (G4) lipase, G3 bilirubin, and G4 amylase elevations. There was no apparent correlation of liver or pancreatic enzyme elevation with drug exposure or the presence of liver metastases. Enavatuzumab exhibited a two-compartment linear PK model. Estimated systemic clearance was 23 to 33 mL/h with an elimination half-life of 7 to 18 days. The predicted target efficacious peak and trough concentrations occurred at 1.0 mg/kg following the second dose. There were no objective responses; 4 patients had stable disease. The MTD of enavatuzumab is 1.0 mg/kg i.v. every 2 weeks. Higher doses were not tolerated due to hepatopancreatic lab abnormalities. Further evaluation of the mechanisms of the liver and pancreatic enzyme toxicities is needed before embarking on further single-agent or combination strategies. Mol Cancer Ther; 17(1); 215-21. ©2017 AACR.

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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
Enavatuzumab Enavatuzumab 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
Enavatuzumab PDL 192 Enavatuzumab (PDL 192) is a monoclonal antibody against tumor necrosis factor-like weak inducer of apoptosis receptor (TWEAKR) that activates innate anti-tumor immune response (PMID: 29075649, PMID: 29054986).
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