Methods of treating brain tumors using combination therapy
Inventors
MURTIE, Joshua • NAGARAJA, NELAMANGALA • NICOLAY, Brandon • SCHENKEIN, David • Yen, Katharine
Assignees
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Publication Number
US-12042497-B2
Publication Date
2024-07-23
Expiration Date
Abstract
Provided are methods of treating a brain tumor in a patient in need thereof comprising administering to the patient a compound described herein and radiation therapy and/or one or more additional therapeutic agents.
Core Innovation
The invention relates to a method for treating an oligodendroglioma or astrocytoma in a patient in need thereof by administering a compound of formula (I) or a pharmaceutically acceptable salt thereof together with one or more additional therapeutic agents in amounts effective for treating the oligodendroglioma or astrocytoma. The compound is identified as Compound A: 6-(6-chloropyridin-2-yl)-N2,N4-bis((R)-1,1,1-trifluoropropan-2-yl)-1,3,5-triazine-2,4-diamine.
The disclosed combination-treatment approach is directed to tumors defined by mutant IDH and the accumulation of R(-)-2-hydroxyglutarate in a patient. The combination includes radiation therapy and/or one or more additional therapeutic agents, with timing described as concurrent versus sequential in relation to radiation.
The invention further encompasses combination regimens designed to show efficacy without antagonism compared to monotherapies and controls. Documented in vivo efficacy is reported showing reduced tumor burden and improved survival versus monotherapies and controls, including in orthotopic IDH1m glioma models and in combination with temozolomide.
Claims Coverage
The partial claim set includes one independent claim, supported by dependent claims that refine the combination regimen by specifying administration timing, dosage constraints for the compound of formula (I), and particular additional therapeutic agents or patient/tumor characterization features. Overall, the claims cover treating oligodendroglioma or astrocytoma using compound of formula (I) in combination with one or more additional therapeutic agents in amounts effective for treatment.
Combination administration for oligodendroglioma or astrocytoma
A method for treating an oligodendroglioma or astrocytoma in a patient in need thereof comprising administering to the patient a compound of formula (I) or a pharmaceutically acceptable salt thereof and one or more additional therapeutic agents in amounts effective for treating the oligodendroglioma or astrocytoma.
Concurrent administration with additional therapeutic agents
The method of administering a compound of formula (I) or a pharmaceutically acceptable salt thereof together with one or more additional therapeutic agents is administered concurrently.
Sequential administration with additional therapeutic agents
The method of administering a compound of formula (I) or a pharmaceutically acceptable salt thereof together with one or more additional therapeutic agents is administered sequentially.
Daily dosage range constraint for compound of formula (I)
The compound of formula (I) or a pharmaceutically acceptable salt thereof is administered in an amount of from 10 to 50 mg/day.
Addition of bevacizumab as the additional therapeutic agent
The one or more additional therapeutic agents is bevacizumab.
IDH1 mutation linked to R(-)-2-hydroxyglutarate accumulation
The oligodendroglioma or astrocytoma is characterized by the presence of an IDH1 mutation that results in accumulation of R(-)-2-hydroxyglutarate in a patient.
Across the independent claim and its dependent refinements, the core claim coverage is a treatment method for oligodendroglioma or astrocytoma using a compound of formula (I) or a pharmaceutically acceptable salt combined with one or more additional therapeutic agents, with further coverage for concurrent or sequential administration, a specified daily dosage range, inclusion of bevacizumab, and tumor characterization involving an IDH1 mutation with R(-)-2-hydroxyglutarate accumulation.
Stated Advantages
Reduced tumor burden versus monotherapies and controls.
Improved survival versus monotherapies and controls.
Reported efficacy without antagonism compared to monotherapies and controls.
In vivo results reported in orthotopic IDH1m glioma models and in combination with temozolomide.
Documented Applications
Treating an oligodendroglioma or astrocytoma in a patient in need thereof using a compound of formula (I) together with one or more additional therapeutic agents.
Combination treatment for brain tumors, including glioma and IDH1/IDH2-mutant gliomas with R(-)-2-hydroxyglutarate accumulation, including approaches involving radiation therapy and/or additional therapeutic agents.
In vivo testing in orthotopic IDH1m glioma models and reporting efficacy, including combination with temozolomide.
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