Treatment of hematological malignancies with menin inhibitors and p-glycoprotein inhibitors
AssigneeKura Oncology, Inc.
InventorsAsako MCCLOSKEY, Francis BURROWS, Shivani MALIK, Douglas GREENE, Xuefeng ZHU, Mollie LEONI
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Abstract
The present disclosure provides methods for treating hematological malignancies using menin inhibitors in combination with P-gp inhibitors and/or BCRP inhibitors. Compositions for use in these methods are also provided.
Claims28
A method for treating a hematological malignancy in a subject in need thereof comprising administering to the subject a menin inhibitor and a cellular efflux transporter inhibitor, optionally selected from a P-glycoprotein (P-gp) inhibitor and a breast cancer resistance protein (BCRP) inhibitor.
A method for treating a hematological malignancy in a subject in need thereof who is being treated with a cellular efflux transporter inhibitor comprising administering to the subject a menin inhibitor, wherein the cellular efflux transporter inhibitor is optionally selected from a P-gp inhibitor and a BCRP inhibitor.
A method for increasing efficacy of a menin inhibitor for treating a hematological malignancy in a subject in need thereof comprising administering to the subject a menin inhibitor and a cellular efflux transporter inhibitor, optionally selected from a P-gp inhibitor or a BCRP inhibitor, optionally wherein efficacy is measured by one or more of CR (MRD+/−), CRh, CR/CRh, CRi, CRp, CRC, ORR, MLFS, PR, SD, OS, blast count levels, DOR, time to relapse, event-free survival, or progression-free survival, and ANC.
A method for increasing bioavailability of a menin inhibitor in a subject comprising administering to the subject the menin inhibitor and a cellular efflux transporter inhibitor, optionally selected from a P-gp inhibitor and a BCRP inhibitor, optionally wherein the subject has a hematological malignancy.
A method of increasing permeability of a menin inhibitor into cells (e.g., cancer cells) or increasing distribution of a menin inhibitor in a tissue (e.g., a cancer tissue, brain tissue, bone marrow, or plasma) in a subject comprising administering to the subject a menin inhibitor and a cellular efflux transporter inhibitor, optionally selected from a P-gp inhibitor and a BCRP inhibitor, wherein the subject optionally has a hematological malignancy.
A kit comprising:
- (1) a therapeutically effective amount of a pharmaceutical composition comprising a menin inhibitor and a pharmaceutically acceptable carrier or excipient, in a first dosage form;
- and (2) a composition comprising a cellular efflux transporter inhibitor, optionally selected from a P-gp inhibitor and a BCRP inhibitor, and a pharmaceutically acceptable carrier or excipient, in a second dosage form.
A pharmaceutical composition comprising 4-methyl-5-((4-((2-(methylamino)-6-((S)-2,2,2-trifluoro-1-hydroxyethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)-1-((S)-2-(4-(methylsulfonyl)piperazin-1-yl)propyl)-1H-indole-2-carbonitrile (Compound IB):
- or a pharmaceutically acceptable form thereof,
- and a pharmaceutically acceptable excipient or carrier.
Dependencies are inferred from the claim text.