AR+breast cancer treatment methods
Inventors
Hattersley, Gary • SAEH, Jamal • YU, Ziyang • Miller, Chris P. • BIHANI, Teeru
Assignees
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Publication Number
US-12329746-B2
Publication Date
2025-06-17
Expiration Date
Abstract
A method for treating AR+ breast cancer in a subject comprising administering to the subject an AR agonist (e.g., SARMs such as RAD140), or in combination with one or more therapeutic agents selected from the group consisting of cdk4/6 inhibitors, m-TOR inhibitors, PI3k inhibitors, PARP inhibitors, BCL-2 inhibitors, and MCL-1 inhibitors.
Core Innovation
The invention relates to methods of treating AR+/ER+/HER2− breast cancer in a subject in need thereof by administering Compound III, or a pharmaceutically acceptable salt or solvate thereof. The disclosed treatment focuses on an androgen receptor (AR) agonist/SARM approach for AR+/ER+ breast cancer, including the use of RAD140 (Compound III) in the disclosed embodiments.
The disclosure addresses treating AR+/ER+/HER2− breast cancer, including settings involving progression and prior exposure to endocrinological agents and/or agents selected from CDK4/6 inhibitors and mTOR inhibitors, and related targeted therapies. The disclosure also includes use cases involving resistant and progressed settings, including fulvestrant-resistant settings referenced in the description summary.
A central feature is combining Compound III therapy with targeted agents, including CDK4/6 inhibitors such as palbociclib and other CDK4/6 inhibitors, and pathway inhibitors targeting PI3K/AKT/mTOR, including mTOR inhibitors such as everolimus. The document further states that ZBTB16 (PLZF) measurement is used to predict or monitor response to AR agonist therapy, where an increase in ZBTB16 after treatment indicates likely responsiveness and continue therapy.
Claims Coverage
The disclosed coverage centers on one independent method claim directed to treating AR+/ER+/HER2− breast cancer by administering Compound III (or a pharmaceutically acceptable salt or solvate). The independent claim is further refined by dependent claims adding patient-selection criteria and combination therapy options, including CDK4/6 inhibitors and agents targeting the PI3K/AKT/mTOR pathway.
Treating AR+/ER+/HER2− breast cancer with Compound III
A method comprising administering to a subject in need thereof Compound III, or a pharmaceutically acceptable salt or solvate thereof, for treating AR+/ER+/HER2− breast cancer.
Treatment of subjects expressing a PI3K mutation
The method further defines the subject as expressing a PI3K mutation.
Adjuvant setting and progression after prior agents
The method is performed in an adjuvant setting and applies to subjects whose disease has progressed after prior treatment with one or more endocrinological agents and/or agents selected from CDK4/6 inhibitors, mTOR inhibitors, BCL-2 inhibitors, PI3K inhibitors, or combinations thereof.
Combination with a CDK4/6 inhibitor
The method further includes administering a CDK4/6 inhibitor as part of the treatment.
Combination with a PI3K/AKT/mTOR pathway targeting agent
The method further includes administering a second therapeutic agent that targets the PI3K/AKT/mTOR pathway, including an mTOR inhibitor and/or a PI3K inhibitor.
Overall, the claim set covers a method of treating AR+/ER+/HER2− breast cancer using Compound III, with dependent coverage for PI3K-mutation selected subjects, an adjuvant/progression context after prior endocrine and targeted therapies, and combination regimens including CDK4/6 inhibitors and PI3K/AKT/mTOR pathway targeting agents.
Stated Advantages
Unexpectedly enhanced tumor growth inhibition versus monotherapy when Compound III is combined with CDK4/6 inhibitors and/or mTOR inhibitors.
Documented Applications
Treating AR+/ER+/HER2− breast cancer in a subject in need thereof, including settings that include disease progression and resistant settings referenced in the description summary, including fulvestrant-resistant settings.
Patient stratification and monitoring or prediction of response to AR agonist therapy using ESR1 mutation/fusion information and a ZBTB16/PLZF biomarker approach, where an increase in ZBTB16 after treatment indicates likely responsiveness and continue therapy.
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