Kinase inhibitor prodrug for the treatment of cancer
AssigneesAuckland Uniservices Limited, Threshold Pharmaceuticals, Inc.
InventorsAdam Vorn Patterson, Jeffrey Bruce Smaill, Shevan Silva, Christopher Paul Guise, Matthew Roy Bull, Victoria Jackson, Tillman Pearce, Nipun Davar
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Abstract
Compositions containing and methods of administering TH-4000 are useful in treatment of cancer alone or in combination with other anti-cancer agents.
Claims27
A pharmaceutically acceptable formulation comprising TH-4000 or a pharmaceutically acceptable salt or solvate thereof and 2-hydroxylpropyl-g-cyclodextrin.
The unit dose of a pharmaceutically acceptable formulation comprising about 75 to about 150 mg of TH-4000.
A method of treating cancer, said method comprising administering TH-4000 in a therapeutically effective dose in the range of about 5 mg/m2 to about 350 mg/m2 to a patient in need of such treatment.
A method for diagnosing an increased risk for tyrosine kinase drug resistance in a subject suffering from a condition or disorder mediated at least in part by EGFR comprising (a) obtaining the genotype of a subject to be treated for an EGFR mediated condition or disorder, or (b) determining the presence of hypoxia;
- and (c) determining whether the subject is at risk for tyrosine kinase drug resistance.
A method of identifying a subject that is susceptible to developing resistance during a course of treatment with a tyrosine kinase inhibitor comprising (a) determining the presence of hypoxia;
- and (b) determining whether the subject is at risk for tyrosine kinase drug resistance.
A method for treating cancer in a subject, comprising the steps of:
- (i) identifying whether the subject is susceptible to tyrosine kinase drug resistance;
- and (ii) administering a therapeutically effective amount of TH-4000 to the subject.
A method for treating cancer in a patient resistant or non-responsive to a dose of a tyrosine kinase inhibitor comprising:
- providing a therapeutic amount of a tyrosine kinase inhibitor;
- and administering the resistance-surmounting quantity of TH-4000 to the patient.
A method for treating cancer in a patient resistant or non-responsive to a dose of a tyrosine kinase inhibitor comprising administering a therapeutic amount of TH-4000 to the patient.
Use of TH-4000 in the manufacture of a medicament for the treatment of cancer in a selected patient population non-responsive to a tyrosine kinase inhibitor, where in the patient population is selected on the basis of the genotype of the patients or the presence of hypoxia.
A kit for use in diagnosing an increased risk for tyrosine kinase drug resistance in a subject suffering from a cancer, comprising:
- (a) a reagent for detecting wild type EGFR;
- or (b) an agent for detecting hypoxia;
- and (c) a container for the reagent or agent;
- and (d) a written product on or in the container describing the use of the reagent or agent in predicting tyrosine kinase resistance in subjects.
Dependencies are inferred from the claim text.