ALK inhibitors for treatment of ALK-negative cancer and plasma cell-mediated diseases

Patent metadata

Field	Value
Publication number	US-12465607-B2
Application number	US-202017772192-A
Country	US
Kind code	B2
Filing date	Mar 12, 2020
Priority date	Oct 28, 2019
Publication date	Nov 11, 2025
Grant date	Nov 11, 2025

Abstract

The present invention provides a method of treating ALK-negative/LTK-positive cancer in a subject, comprising administering to the subject a pharmaceutically-effective dose of a linear inhibitor of ALK. The invention is of particular utility in treating multiple myeloma, including proteasome inhibitor-resistant multiple myeloma.

First claim

The invention claimed is:

1 . A method of treating a subject suffering from:
(i) an anaplastic lymphoma kinase (ALK)-negative and leukocyte tyrosine kinase (LTK)-positive (ALK Neg LTK Pos ) cancer selected from multiple myeloma or chronic lymphocytic leukaemia; or ii) a plasma cell-mediated disease mediated by ALK Neg LTK Pos Pos plasma cells, selected from an autoimmune disease or graft versus host disease (GVHD), wherein said cancer or plasma cell-mediated disease is characterised by antibody hypersecretion by said ALK Neg LTK Pos cancer or plasma cells, said method comprising administering to said subject a pharmaceutically-effective dose of an ALK inhibitor selected from ceritinib, brigatinib, crizotinib, ensartinib, alectinib and entrectinib.

2 . The method of claim 1 , wherein said cancer is multiple myeloma.

3 . The method of claim 1 , wherein said cancer is chronic lymphocytic leukaemia.

4 . The method of claim 1 , wherein said cancer is resistant to treatment with a proteasome inhibitor.

5 . The method of claim 4 , wherein said proteasome inhibitor is bortezomib.

6 . The method of claim 1 , wherein said autoimmune disease is lupus or immune thrombocytopenia.

7 . The method of claim 1 , wherein said treatment comprises daily administration of a dose comprising 450 mg ceritinib, and said dose is administered orally.

8 . The method of claim 1 , wherein said treatment comprises daily administration of a dose comprising 200 mg to 400 mg ceritinib, and said dose is administered orally.

9 . The method of claim 1 , wherein said treatment is for multiple myeloma, and wherein said treatment comprises daily administration of a dose comprising 400 mg to 500 mg ceritinib, and said dose is administered orally.

10 . The method of claim 1 , wherein said subject is a human.

11 . A method of diagnosing and treating a subject suffering from an anaplastic lymphoma kinase (ALK)-negative and leukocyte tyrosine kinase (LTK)-positive (ALK Neg LTK Pos ) cancer selected from multiple myeloma or chronic lymphocytic leukemia, wherein said cancer is characterised by antibody hypersecretion by said ALK Neg LTK Pos cancer cells, comprising:
(i) diagnosing cancer in said subject; (ii) testing said cancer for expression of ALK and LTK; and (iii) when said cancer is found to be ALK-negative and LTK-positive, administering a pharmaceutically-effective dose of an ALK inhibitor selected from ceritinib, brigatinib, crizotinib, ensartinib, alectinib and entrectinib to said subject.

12 . A method of diagnosing and treating a subject suffering from an anaplastic lymphoma kinase (ALK)-negative and leukocyte tyrosine kinase (LTK)-positive (ALK Neg LTK Pos ) cancer selected from multiple myeloma or chronic lymphocytic leukaemia, wherein said cancer is characterised by antibody hypersecretion by said ALK Neg LTK Pos cancer cells, comprising:
(i) diagnosing cancer in said subject; (ii) determining that said cancer is ALK-negative and LTK-positive; and
administering to said subject an ALK inhibitor selected from ceritinib, brigatinib, crizotinib, ensartinib, alectinib and entrectinib in an amount effective to treat said cancer.

Assignees

• Univ Oslo

Inventors

• Farhan Hesso
• Munthe Ludvig
• Tasken Kjetil
• Skanland Sigrid
• Giliberto Mariaserena
• Hellem Schjesvold Fredrik
• Driessen Christoph
• Besse Lenka
• Besse Andrej

Classifications

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• A61K31/4545

  containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine · CPC title