Granted Patent
B2
US 12,329,746 · App. 18/478,029 · Granted Jun 17, 2025
AR+breast cancer treatment methods
Inventors:
Gary Hattersley (Stow, MA); Jamal Saeh (Belmont, MA); Ziyang Yu (Wellesley, MA); Chris P. Miller (San Mateo, CA); Teeru Bihani (Boston, MA)
Assignee:
Ellipses Pharma Ltd
View Patent ↗
Loading inventors, assignments & file history…
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.
Claims (35)
1. A method of treating AR+/ER+/HER2− breast cancer in a subject in need thereof, the method comprising administering to the subject a compound which is Compound III:
or a pharmaceutically acceptable salt or solvate thereof.
2. The method according to claim 1 , wherein the compound is administered via an oral route.
3. The method according to claim 1 , wherein:
(i) the subject is treated in an adjuvant setting;
(ii) the subject has had disease progression after treatment with one or more endocrinological agents; and/or
(iii) said subject has had disease progression after treatment with one or more agents selected from the group consisting of CDK4/6 inhibitors, mTOR inhibitors, BCL-2 inhibitors, PI3K inhibitors, and combinations thereof.
4. The method according to claim 1 , wherein the breast cancer is resistant to at least one prior therapy.
5. The method according to claim 1 , wherein the subject has progressed on prior endocrine therapy.
6. The method according to claim 1 , wherein the subject is a candidate for first line treatment.
7. The method according to claim 1 , wherein the compound is dosed between 10 and 500 mg, 10 mg and 250 mg, or 25 mg and 250 mg per day; optionally wherein the dose is once per day.
8. The method according to claim 1 , wherein the subject expresses ESR1 comprising one or more mutations.
9. The method according to claim 8 , wherein the one or more mutations is selected from the group consisting of ESR1-AKAP12, ESR1-CCDCl70, ESR1-YAP1, ESR1-POLH, ESR1-PCDH1 IX, and combinations thereof.
10. The method according to claim 1 , wherein the subject expresses a PI3K mutation.
11. The method according to claim 10 , wherein the PI3K mutation is PIK3CA.
12. The method according to claim 1 , wherein the treatment further comprises the administration of a CDK4/6 inhibitor.
13. The method according to claim 12 , wherein said CDK4/6 inhibitor is selected from the group consisting of palbociclib, ribociclib, trilaciclib, abemaciclib and AMG925.
14. The method according to claim 1 , wherein said treatment further comprises the administration of a second therapeutic agent that targets the PI3K/AKT/mTOR pathway, for example:
(i) an mTOR inhibitor; optionally wherein said mTOR inhibitor is selected from the group consisting of sirolimus, temsirolimus, everolimus, ridafarolimus, and MLN0128; and/or
(ii) a PI3K inhibitor; optionally wherein said PI3K inhibitor is BEZ235, GDC-0980, GDC-0941, BYL719, MK2206, GDC-0068, GSK2110183, GSK2141795, AZD5363, AZD2014, MLN0128 or CC-223.
15. The method according to claim 1 , wherein said treatment further comprises the administration of:
(i) a PARP inhibitor, for example talazoparib, veliparib, niraparib, beigene290, E7449, KX01, ABT767, CK102, JPI289, KX02, IMP4297, SC10914, NT125, PJ34, VPI289 or ANG-3186;
(ii) a MCL-1 inhibitor; optionally wherein said MCL-1 inhibitor is 7-(5-((4-(4-(N,N-Dimethylsulfamoyl)piperazin-1-yl)phenoxy)methyl)-1,3-dimethyl-1H-pyrazol-4-yl)-1-(2-morpholinoethyl)-3-(3-(naphthalen-1-yloxy)propyl)-1H-indole-2-carboxylic Acid, S63845, omacataxine, seliciclib, UMI-77, AT101, or sabutoclax; and/or
(iii) a BCL-2 inhibitor, for example venetoclax, navitoclax, ABT737, G3139 or S55746.
16. The method according to claim 1 , wherein said treatment further comprises the administration of a therapeutic agent selected from the group consisting of rapamycin, everolimus, ridaforolimus, temsirolimus, MLN0128, CC115, CC223, OSI-027, AZD8055, AZD2014, GDC-0980, SAR245409, LY3023414, NVP-BEZ235, NVP-BGT226, SF1126 and PKI-587.
17. The method according to claim 1 , wherein the treatment further comprises administration of a therapeutic agent selected from the group consisting of everolimus, BYL719, GDC-0068, palbociclib, AZD5363 and abemaciclib and combinations thereof.
18. The method according to claim 1 , wherein the treatment further comprises the administration of everolimus.
19. The method according to claim 1 , wherein the treatment further comprises the administration of BYL719.
20. The method according to claim 13 , wherein the CDK4/6 inhibitor is palbociclib.
21. The method according to claim 13 , wherein said CDK4/6 inhibitor is ribociclib.
22. The method according to claim 13 , wherein said CDK4/6 inhibitor abemaciclib.
23. The method according to claim 1 , wherein said subject is a woman.
24. The method according to claim 1 , wherein said breast cancer is localized, advanced or metastatic.
25. The method according to claim 3 , wherein said one or more endocrinological agents are selected from the group consisting of SERMs, SERDs, progestins, aromatase inhibitors, and combinations thereof.
26. The method according to claim 23 , wherein said woman is a premenopausal woman or a post menopausal woman.
Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 12, 2024
From: HATTERSLEY, GARY; SAEH, JAMAL; YU, ZIYANG; MILLER, CHRIS; BIHANI, TEERU
To: RADIUS HEALTH, INC.
Reel/Frame 066733/0022 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 12, 2024
From: RADIUS HEALTH, INC.
To: RADIUS PHARMACEUTICALS, INC.
Reel/Frame 066733/0027 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 12, 2024
From: RADIUS PHARMACEUTICALS, INC.
To: ELLIPSES PHARMA LTD
Reel/Frame 066733/0039 →
Continuity (6)
Provisional Application
62461546
· Feb 21, 2017
Provisional Application
62377497
· Aug 19, 2016
Provisional Application
62353350
· Jun 22, 2016
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