Methods of treating cancer patients with farnesyltransferase inhibitors

Patent metadata

Field	Value
Publication number	US-2017304291-A1
Application number	US-201715643387-A
Country	US
Kind code	A1
Filing date	Jul 6, 2017
Priority date	Aug 17, 2015
Publication date	Oct 26, 2017
Grant date	—

Abstract

The present invention relates to the field of molecular biology and cancer biology. Specifically, the present invention relates to methods of treating a subject with a farnesyltransferase inhibitor (FTI) that include determining whether the subject is likely to be responsive to the FTI treatment based on genotyping and expression profiling of certain immunological genes and RAS mutation status in the subject.

First claim

We claim:

1 . A method of treating a H-Ras mutant HNSCC in a subject, consisting of administering a therapeutically effective amount of tipifarnib to said subject, wherein said HNSCC is at an advanced stage, metastatic, relapsed or refractory.

2 . The method of claim 1 , wherein the H-Ras mutation of said subject comprises an amino acid substitution at a codon selected from the group consisting of G12, G13, and Q61.

3 . The method of claim 1 , comprising determining the presence of H-Ras mutation in a sample from said subject.

4 . The method of claim 3 , wherein said sample is a tumor biopsy.

5 . The method of claim 3 , wherein said H-Ras mutation is determined by a method selected from the group consisting of sequencing, Polymerase Chain Reaction (PCR), DNA microarray, Mass Spectrometry (MS), Single Nucleotide Polymorphism (SNP) assay, denaturing high-performance liquid chromatography (DHPLC), and Restriction Fragment Length Polymorphism (RFLP) assay.

6 . The method of claim 1 , wherein tipifarnib is administered at a dose of 1-1000 mg/kg body weight.

7 . The method of claim 1 , wherein tipifarnib is administered twice a day.

8 . The method of claim 1 , wherein tipifarnib is administered at a dose of 600 mg twice a day.

9 . The method of claim 1 , wherein tipifarnib is administered at a dose of 900 mg twice a day.

10 . The method of claim 1 , wherein tipifarnib is administered for a period of one to seven days.

11 . The method of claim 1 , wherein tipifarnib is administered on days 1-7 and 15-21 of a 28-day treatment cycle.

12 . The method of claim 1 , wherein tipifarnib is administered at a dose of 600 mg twice a day on days 1-7 and 15-21 of a 28-day treatment cycle.

13 . The method of claim 1 , wherein tipifarnib is administered at a dose of 900 mg twice a day on days 1-7 and 15-21 of a 28-day treatment cycle.

14 . The method of claim 1 , wherein tipifarnib is administered at a dose of 300 mg twice a day for 3 of 4 weeks in repeated 4 week cycles.

15 . A method of treating a H-Ras mutant relapsed or refractory head and neck squamous cell carcinoma (HNSCC) in a subject, comprising administering a therapeutically effective amount of tipifarnib to said subject.

16 . The method of claim 15 , wherein the H-Ras mutation of said subject comprises an amino acid substitution at a codon selected from the group consisting of G12, G13, and Q61.

17 . The method of claim 15 , comprising determining the presence of H-Ras mutation in a sample from said subject.

18 . The method of claim 17 , wherein said sample is a tumor biopsy.

19 . The method of claim 17 , wherein said H-Ras mutation is determined by a method selected from the group consisting of sequencing, Polymerase Chain Reaction (PCR), DNA microarray, Mass Spectrometry (MS), Single Nucleotide Polymorphism (SNP) assay, denaturing high-performance liquid chromatography (DHPLC), and Restriction Fragment Length Polymorphism (RFLP) assay.

20 . The method of claim 15 , wherein tipifarnib is administered at a dose of 1-1000 mg/kg body weight.

21 . The method of claim 15 , wherein tipifarnib is administered twice a day.

22 . The method of claim 15 , wherein tipifarnib is administered at a dose of 600 mg twice a day.

23 . The method of claim 15 , wherein tipifarnib is administered at a dose of 900 mg twice a day.

24 . The method of claim 15 , wherein tipifarnib is administered for a period of one to seven days.

25 . The method of claim 15 , wherein tipifarnib is administered on days 1-7 and 15-21 of a 28-day treatment cycle.

26 . The method of claim 15 , wherein tipifarnib is administered at a dose of 600 mg twice a day on days 1-7 and 15-21 of a 28-day treatment cycle.

27 . The method of claim 15 , wherein tipifarnib is administered at a dose of 900 mg twice a day on days 1-7 and 15-21 of a 28-day treatment cycle.

28 . The method of claim 15 , wherein tipifarnib is administered at a dose of 300 mg twice a day for 3 of 4 weeks in repeated 4 week cycles.

29 . The method of claim 15 , further comprising administering a therapeutically effective amount of a second active agent or a support care therapy.

30 . The method of claim 29 , wherein said second active agent is (i) selected from the group consisting of a DNA-hypomethylating agent, a therapeutic antibody that specifically binds to a cancer antigen, a hematopoietic growth factor, a cytokine, an antibiotic, a cox-2 inhibitor, an immunomodulatory agent, an anti-thymocyte globulin, an immunosuppressive agent, and a corticosteroid or a pharmacological derivative thereof; or (ii) an anti-PD1 antibody or an anti-PDL1 antibody.

Assignees

• Kura Oncology Inc

Inventors

• Gualberto Antonio
• Scholz Catherine Rose

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title