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US 2022/0088016 A1Published application
Cancer treatment using multi-targeted kinase inhibitor in combination of protein kinase biomarkers
AssigneeZhejiang Crownmab Biotech Co. Ltd.
InventorsLan YANG, Qian SHI, Guoliang YU
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Abstract
Provided herein are methods of treating cancer in a patient with a tyrosine kinase inhibitor. The method comprises: a) measuring the expression level of a protein kinase in a sample obtained from the patient; b) comparing the expression level of the protein kinase to a corresponding reference expression level; c) determining a likelihood of the patient being responsive to the tyrosine kinase inhibitor; and d) treating the patient whose expression level of the protein kinase indicates that the patient will be responsive with the tyrosine kinase inhibitor.
Claims19
A method for treating cancer in a patient with a tyrosine kinase inhibitor, the method comprising:
- a) measuring the expression level of a first protein kinase in a sample obtained from the patient;
- b) comparing the expression level of the first protein kinase to a corresponding reference expression level;
- c) determining a likelihood of the patient being responsive to the tyrosine kinase inhibitor;
- and
- d) treating the patient whose expression level of the first protein kinase indicates that the patient will be responsive with the tyrosine kinase inhibitor,
- wherein the tyrosine kinase inhibitor is a compound of formula (I) or a pharmaceutically acceptable salt thereof
- wherein:
- R1 is hydrogen, C1-6 alkyl, C1-6 haloalkyl halo or cyano;
- M is CH or N;
- L is O, NH or N(CH3);
- A is CR5 or N;
- W is CR6 or N;
- R2, R5 and R6 are independently hydrogen, C1-6 alkyl, C1-6 haloalkyl, halo, C3-7 cycloalkyl or cyano;
- X, Y, and Z are independently CH or N;
- and
- R3 and R4 are independently hydrogen, halo, cyano, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, hydroxyl-C1-6 alkyl, di-(C1-6 alkylamino)-C1-6 alkyl, amino, C1-6 alkylamino, C3-7 cycloalkylamino, di-(C1-6 alkyl)amino, amino-C1-6 alkylamino, C1-6 alkoxy-C1-6 alkylamino, C1-6 alkoxycarbonyl-C1-6 alkylamino, di-(C1-6 alkoxy-C1-6 alkyl)amino, aminocarbonyl, C1-6 alkylaminocarbonyl, di-(C1-6 alkyl)aminocarbonyl, C3-7 cycloalkylaminocarbonyl, C1-6 alkoxy, C3-7 cycloalkoxy, hydroxyl-C1-6 alkoxy, C1-6 haloalkoxy, amino-C1-6 alkyl, amino-C1-6 alkoxy, C1-6 alkylsulfonyl, C2-6 alkenylsulfonyl, C3-7 cycloalkylsulfonyl, heterocyclyl optionally substituted by B, aryl optionally substituted by B, heteroaryl optionally substituted by B, C1-6 alkylsulfonylamino, C2-6 alkenylsulfonylamino, C3-7 cyclooalkylsulfonylamino, amido, C1-6 alkylcarbonylamino, C2-6 alkenylcarbonylamino, C3-7 cyclooalkylcarbonylamino, C1-6 alkoxycarbonylamino, C3-7 cycloalkoxycarbonylamino, ureido, C3-7 cycloalkyl, C3-7 halocycloalkyl, heterocyclyloxy, piperidinylamino, N-methyl-piperidinyl-4-carbonyl, piperazinyl-C1-6 alkyl, pyrrolylcarbonylamino, N-methyl-piperidinylcarbonylamino or heterocyclyl-C1-6 alkoxy;
- or
- R3 and R4 together form a 3 to 8-membered ring with the atoms in the aromatic ring to which they are attached;
- and
- B is hydrogen, C1-6 alkyl, C1-6 haloalkyl, halo, hydroxyl, aryl, amino, C1-6 alkylamino, C3-7 cycloalkylamino, di-(C1-6 alkyl)amino, cyano, or C3-7 cycloalkyl.
17 more elements
4-9. (canceled)
A method for continuing a cancer therapy in a patient comprising:
- a) treating the patient with a tyrosine kinase inhibitor;
- b) obtaining a tumor sample from the patient;
- c) measuring the expression level of a first protein kinase;
- d) comparing the expression level of the first protein kinase to a corresponding reference expression level;
- e) determining a likelihood of the patient being responsive to the tyrosine kinase inhibitor;
- and
- f) continuing treatment of the cancer when the expression level of the first protein kinase in the tumor sample demonstrates responsiveness,
- wherein the tyrosine kinase inhibitor is a compound of formula (I) or a pharmaceutically acceptable salt thereof
- wherein:
- R1 is hydrogen, C1-6 alkyl, C1-6 haloalkyl, halo or cyano;
- M is CH or N;
- L is O;
- NH or N(CH3);
- A is CR5 or N;
- W is CR6 or N;
- R2, R5 and R6 are independently hydrogen, C1-6 alkyl, C1-6 haloalkyl, halo, C3-7 cycloalkyl or cyano;
- X, Y, and Z are independently CH or N;
- and
- R3 and R4 are independently hydrogen, halo, cyano, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, hydroxyl-C1-6 alkyl, di-(C1-6 alkylamino)-C1-6 alkyl, amino, C1-6 alkylamino, C3-7 cycloalkylamino, di-(C1-6 alkyl)amino, amino-C1-6 alkylamino, C1-6 alkoxy-C1-6 alkylamino, C1-6 alkoxycarbonyl-C1-6 alkylamino, di-(C1-6 alkoxy-C1-6 alkyl)amino, aminocarbonyl, C1-6 alkylaminocarbonyl, di-(C1-6 alkyl)aminocarbonyl, C3-7 cycloalkylaminocarbonyl, C1-6 alkoxy, C3-7 cycloalkoxy, hydroxyl-C1-6 alkoxy, C1-6 haloalkoxy, amino-C1-6 alkyl, amino-C1-6 alkoxy, C1-6 alkylsulfonyl, C2-6 alkenylsulfonyl, C3-7 cycloalkylsulfonyl, heterocyclyl optionally substituted by B, aryl optionally substituted by B, heteroaryl optionally substituted by B, C1-6 alkylsulfonylamino, C2-6 alkenylsulfonylamino, C3-7 cyclooalkylsulfonylamino, amido, C1-6 alkylcarbonylamino, C2-6 alkenylcarbonylamino, C3-7 cyclooalkylcarbonylamino, C1-6 alkoxycarbonylamino, C3-7 cycloalkoxycarbonylamino, ureido, C3-7 cycloalkyl, C3-7 halocycloalkyl, heterocyclyl-oxy, piperidinylamino, N-methyl-piperidinyl-4-carbonyl, piperazinyl-C1-6 alkyl, pyrrolylcarbonylamino, N-methyl-piperidinylcarbonylamino or heterocyclyl-C1-6 alkoxy:
- or
- R3 and R4 together form a 3 to 8-membered ring with the atoms in the aromatic ring to which they are attached;
- and
- B is hydrogen, C1-6 alkyl, C1-6 haloalkyl, halo, hydroxyl, aryl, amino, C1-6 alkylamino, C3-7 cycloalkylamino, di-(C1-6 alkyl)amino, cyano, or C3-7 cycloalkyl.
20 more elements
18-21. (canceled)
26-29. (canceled)
Dependencies are inferred from the claim text.