IP Library › Granted Patent US 12,370,181
Granted Patent B2
US 12,370,181 · App. 17/625,184 · Granted Jul 29, 2025

Regimens of estrogen receptor antagonists

Inventors: Cyrus L. Harmon (Bolinas, CA); Peter J. Kushner (San Francisco, CA); David C. Myles (Berkeley, CA); Leslie Hodges Gallagher (Alameda, CA); Richard Sun (San Francisco, CA)
Assignee: Olema Pharmaceuticals, Inc.
A61K31/437A61K31/565A61K45/06A61P35/00
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,370,181
App. No.
17/625,184
Granted
Jul 29, 2025
Kind
B2
Abstract

Provided herein are methods of administering estrogen receptor antagonists for use in treatment of cancer. In some embodiments, estrogen receptor antagonists provided herein are tetrahydro pyrido[3,4-b] indole compounds. In some embodiments, provided antagonists are complete estrogen receptor antagonists.

Claims (11)

1. A method of treating a subject suffering from a cancer characterized by a mutation of Estrogen Receptor 1 (ESR1), the method comprising administering to the subject Compound 1:

or a pharmaceutically acceptable salt thereof, wherein the mutation is an activation mutation, wherein the activation mutation is D538G or Y537S.

2. The method of claim 1 , wherein the subject is receiving or has received a secondary agent and the secondary agent is a CDK4/6 inhibitor.

3. The method of claim 2 , wherein the CDK4/6 inhibitor is selected from palbociclib, ribociclib, abemaciclib, lerociclib, and trilaciclib.

4. The method of claim 3 , wherein the CDK4/6 inhibitor is palbociclib.

5. The method of claim 1 , wherein the subject is receiving or has received a secondary agent and the secondary agent is a PIK3CA inhibitor.

6. The method of claim 5 , wherein the PIK3CA inhibitor is selected from alpelisib and taselisib.

7. The method of claim 1 , wherein the subject is receiving or has received a secondary agent and the secondary agent is an mTOR inhibitor.

8. The method of claim 7 , wherein the mTOR inhibitor is selected from sirolimus, temsirolimus, and everolimus.

9. The method of claim 1 , wherein the activation mutation is D538G.

10. The method of claim 1 , wherein the activation mutation is Y537S.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 7, 2022
From: HARMON, CYRUS L.; KUSHNER, PETER J.; MYLES, DAVID C.; GALLAGHER, LESLIE HODGES; SUN, RICHARD
To: OLEMA PHARMACEUTICALS, INC.
Reel/Frame 059190/0265 →
Continuity (4)
Provisional Application 62871592 · Jul 8, 2019
Provisional Application 62871191 · Jul 7, 2019
Related Publication 20220265616A1 · Aug 25, 2022
Related Publication 20230109666A2 · Apr 6, 2023
References Cited (180)
US 4418068A · Jones · 1983 [cited by applicant]
US 4659516A · Bowler et al. · 1987 [cited by applicant]
US 5362718A · Skotnicki et al. · 1994 [cited by applicant]
US 5393763A · Black et al. · 1995 [cited by applicant]
US 5457117A · Black et al. · 1995 [cited by applicant]
US 5478847A · Draper · 1995 [cited by applicant]
US 5780497A · Miller et al. · 1998 [cited by applicant]
US 5880137A · Miller et al. · 1999 [cited by applicant]
US 5998402A · Miller et al. · 1999 [cited by applicant]
US 6005102A · Raveendranath et al. · 1999 [cited by applicant]
US 6326392B1 · Gast et al. · 2001 [cited by applicant]
US 6479535B1 · Pickar et al. · 2002 [cited by applicant]
US 6512002B2 · Lee et al. · 2003 [cited by applicant]
US 6583170B1 · Pickar et al. · 2003 [cited by applicant]
US 6632834B2 · Thompson et al. · 2003 [cited by applicant]
US 6756401B2 · Day et al. · 2004 [cited by applicant]
US 6774122B2 · Evans et al. · 2004 [cited by applicant]
US 6777424B2 · Littman · 2004 [cited by applicant]
US 6821989B2 · Rosati · 2004 [cited by applicant]
US 6936612B2 · Barvian et al. · 2005 [cited by applicant]
US 7456160B2 · Evans et al. · 2008 [cited by applicant]
US 8227462B2 · Fairhurst et al. · 2012 [cited by applicant]
US 8299112B2 · Smith et al. · 2012 [cited by applicant]
US 8455534B2 · Smith et al. · 2013 [cited by applicant]
US 8703810B2 · Kahraman et al. · 2014 [cited by applicant]
US 8853423B2 · Govek et al. · 2014 [cited by applicant]
US 9018244B2 · Kushner et al. · 2015 [cited by applicant]
US 9078871B2 · Kahraman et al. · 2015 [cited by applicant]
US 9540361B2 · Dijcks et al. · 2017 [cited by applicant]
US 10292971B2 · Myles · 2019 [cited by examiner]
US 10624878B2 · Myles · 2020 [cited by examiner]
US 11229630B2 · Myles et al. · 2022 [cited by applicant]
US 20010056099A1 · Day et al. · 2001 [cited by applicant]
US 20020013327A1 · Lee et al. · 2002 [cited by applicant]
US 20020016340A1 · Rosati · 2002 [cited by applicant]
US 20020128276A1 · Day et al. · 2002 [cited by applicant]
US 20050272759A1 · Moon et al. · 2005 [cited by applicant]
US 20050282849A1 · Moon et al. · 2005 [cited by applicant]
US 20120157402A1 · Cao et al. · 2012 [cited by applicant]
US 20120238755A1 · Ueda et al. · 2012 [cited by applicant]
US 20130178445A1 · Kushner et al. · 2013 [cited by applicant]
US 20140357661A1 · Bradbury et al. · 2014 [cited by applicant]
US 20150005286A1 · Smith et al. · 2015 [cited by applicant]
US 20150258080A1 · Hager et al. · 2015 [cited by applicant]
US 20160175289A1 · Labadie et al. · 2016 [cited by applicant]
US 20170362228A1 · Labadie et al. · 2017 [cited by applicant]
US 20180002344A1 · Labadie et al. · 2018 [cited by applicant]
US 20180214393A1 · Hattersley · 2018 [cited by applicant]
US 20180235945A1 · Labadie et al. · 2018 [cited by applicant]
US 20180289679A1 · Myles et al. · 2018 [cited by applicant]
US 20190247372A1 · Myles et al. · 2019 [cited by applicant]
US 20210059991A1 · Myles et al. · 2021 [cited by applicant]
US 20220370421A1 · Myles et al. · 2022 [cited by applicant]
US 20230129598A1 · Harmon et al. · 2023 [cited by applicant]
EP 0705832A1 · 1996 [cited by applicant]
EP 0802184A1 · 1997 [cited by applicant]
WO WO1999024027A2 · 1999 [cited by applicant]
WO WO2002003975A2 · 2002 [cited by applicant]
WO WO2002003976A2 · 2002 [cited by applicant]
WO WO2002003977A2 · 2002 [cited by applicant]
WO WO2002003986A2 · 2002 [cited by applicant]
WO WO2002003988A2 · 2002 [cited by applicant]
WO WO2002003989A2 · 2002 [cited by applicant]
WO WO2002003990A2 · 2002 [cited by applicant]
WO WO2002003991A2 · 2002 [cited by applicant]
WO WO2002003992A2 · 2002 [cited by applicant]
WO WO2002004418A2 · 2002 [cited by applicant]
WO WO2002013802A2 · 2002 [cited by applicant]
WO WO03016270A2 · 2003 [cited by applicant]
WO WO2005089764A1 · 2005 [cited by applicant]
WO WO2006078834A1 · 2006 [cited by applicant]
WO WO2008127715A1 · 2008 [cited by applicant]
WO WO2010138695A1 · 2010 [cited by applicant]
WO WO2010138706A1 · 2010 [cited by applicant]
WO WO2010138758A1 · 2010 [cited by applicant]
WO WO2011156518A2 · 2011 [cited by applicant]
WO WO2012084711A1 · 2012 [cited by applicant]
WO WO2013090921A1 · 2013 [cited by applicant]
WO WO2014191726A1 · 2014 [cited by applicant]
WO WO2014203129A1 · 2014 [cited by applicant]
WO WO2014203132A1 · 2014 [cited by applicant]
WO WO2014205136A1 · 2014 [cited by applicant]
WO WO2014205138A1 · 2014 [cited by applicant]
WO WO2015149045A1 · 2015 [cited by applicant]
WO WO2016097072A1 · 2016 [cited by applicant]
WO WO2017059139A1 · 2017 [cited by applicant]
WO WO2018064231A1 · 2018 [cited by applicant]
WO WO2018077630A1 · 2018 [cited by applicant]
WO WO2018197653A1 · 2018 [cited by applicant]
WO WO2019245974A1 · 2019 [cited by applicant]
WO WO2020014435A1 · 2020 [cited by applicant]
WO WO2020014440A1 · 2020 [cited by applicant]
WO WO2020023297A1 · 2020 [cited by applicant]
WO WO2020037203A2 · 2020 [cited by applicant]
WO WO2021007146A1 · 2021 [cited by applicant]
WO WO2021178846A1 · 2021 [cited by applicant]
Alemany, C. et al., A Phase 1/2 Dose Escalation and Expansion Study of OP-1250 in Adults with Advanced and/or Metastatic Hormone Receptor-positive (HR+), HER2-negative (HER2-) Breast Cancer (NCT04505826), presented at A… [cited by applicant]
Arao, Y and Korach, K. S. et al., The F domain of estrogen receptor a is involved in species-specific, tamoxifen-mediated transactivation, J. Biol. Chem., 293(22):8495-8507 (2018). [cited by applicant]
Olema Oncology, Complete Estrogen Receptor (ER) Antagonism As An Optimal Approach for ER-Positive Breast Cancer Drug Development, presented at the 2021 JCA-AACR Precision Cancer Medicine International Conference, Sep. 1… [cited by applicant]
Bardia, A. et al., Evaluation of RAD1901, a novel investigational, selective estrogen receptor degrader (SERD), for the treatment of ER-positive (ER+) advanced breast cancer, Journal of Clinical Oncology, Meeting Abstra… [cited by applicant]
Bentrem, D. J. et al, Molecular mechanism of action at estrogen receptor alpha of a new clinically relevant antiestrogen (GW7604) related to tamoxifen, Endocrinology, 142(2): 838-46 (2001). [cited by applicant]
Blizzard, T.A. et al., Estrogen receptor ligands. Part 14: Application of novel antagonist side chains to existing platforms, Bioorganic & Medicinal Chemistry Letters, 15:5124-5128 (2005). [cited by applicant]
Cardoso, F. et al., 3rd ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3), Annals of Oncology, 28:16-33 (2017). [cited by applicant]
Clinical Trials, A Dose Escalation/Expansion Study of Oral OP-1250 in Subjects With Advanced and/or Metastatic HR+, HER2− Breast Cancer, NCT04505826, 4 pages (2022). [cited by applicant]
Clinical Trials, A Phase 1 Study of Oral OP-1250 in Combination With Palbociclib in HR+/HER2− Breast Cancer Patients, NCT05266105, 7 pages (2022). [cited by applicant]
Dardes, R. C. et al, Effects of a New Clinically Relevant Antiestrogen (GW5638) Related to Tamoxifen on Breast and Endometrial Cancer Growth in Vivo, Clinical Cancer Research, 8:1995-2001 (2002). [cited by applicant]
De Savi, C. et al., Optimization of a Novel Binding Motif to (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1 H-pyrido[3,4-b ]indol-1-yl)phenyl)acrylic Acid (AZD9496), a Potent an… [cited by applicant]
Dickler, M. et al., Abstract CT231: A first-in-human phase I study to evaluate the oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with estrogen receptor+ HER2−, advanced/metastatic … [cited by applicant]
Fan, M. et al, Characterization of molecular and structural determinants of selective estrogen receptor downregulators, Breast Cancer Res. Treat, 103: 37-44 (2007). [cited by applicant]
Fribbens, C. et al., Plasma ESR1 Mutations and the Treatment of Estrogen Receptor-Positive Advanced Breast Cancer, Journal of Clinical Oncology, 34(25):961-2968 (2020). [cited by applicant]
Gelsomino, L. et al., ESR1 mutations affect anti-proliferative responses to tamoxifen through enhanced cross-talk with IGF signaling, Breast Cancer Res Treat, 157:253-265 (2016). [cited by applicant]
Goetz, M., Bringing the Investigational Breast Cancer Drug Endoxifen from Bench to Bedside with NCI Support, National Cancer Institute, 1-7 (2017). [cited by applicant]
Guan, J. et al., Therapeutic Ligands Antagonize Estrogen Receptor Function by Impairing Its Mobility, Cell, 178: 1-15 (2019). [cited by applicant]
Hall, J. and McDonnell, D. et al., Coregulators in Nuclear Estrogen Receptor Action, Duke University, Department of Pharmacology and Cancer Biology, 5(6):1-15 (2005). [cited by applicant]
Hamilton, E. et al., A First-in-Human Study of the New Oral Selective Estrogen Receptor Degrader AZD9496 for ER+/HER2− Advanced Breast Cancer, Clinical Cancer Research, 24(15):1-9 (2018). [cited by applicant]
Hamilton, E. et al., Abstract #1167, A Phase I/II Open-label, First-in-Human, Multicenter, Dose Escalation and Dose Expansion Study of OP-1250 monotherapy in adult subjects with locally advanced, recurrent, and metastat… [cited by applicant]
Hamilton, E. et al., Abstract OT-09-10: A phase I/II open-label, first-in-human, multicenter, dose escalation and dose expansion study of OP-1250 monotherapy in adult subjects with advanced and/or metastatic hormone rec… [cited by applicant]
Heldring, N. et al., Estrogen Receptor: How Do They Signal and What Are Their Targets, Physiol. Rev., 87: 905-931 (2007). [cited by applicant]
Hewitt, S. and Korach, K. S., Estrogen Receptors: New Directions in the New Millennium, Endocr Rev., 39(5):664-675 (2018). [cited by applicant]
Hodges-Gallagher, L. et al., Abstract #1410: The Complete Estrogen Receptor Antagonist OP-1250 Shrinks Tumors in Xenograft Models and Has Favorable Preclinical Pharmacokinetic Attributes, Olema Oncology, presented at th… [cited by applicant]
Hodges-Gallagher, L. et al., Abstract #4376: OP-1250, a complete estrogen receptor antagonist (CERAN) that shrinks estrogen receptor positive tumors and exhibits favorable pharmacokinetics, Cancer Res., 80(Supp 16):1-4 … [cited by applicant]
Hodges-Gallagher, L. et al., Abstract LB122: The complete estrogen receptor antagonist (Ceran) OP-1250 shrinks ER+ brain metastases in an intracranial xenograft tumor model expressing mutant ESR1, Cancer Res., 81 (Supp … [cited by applicant]
Hodges-Gallagher, L. et al., Abstract P5-05-02: Preclinical development of OP-1250, an oral complete estrogen receptor antagonist (CERAN) that shrinks ER-positive breast tumors in xenograft models, Cancer Res., 80(Supp … [cited by applicant]
Hodges-Gallagher, L. et al., Abstract PS18-16: The complete estrogen receptor antagonist OP-1250 shrinks tumors in xenograft models and has favorable preclinical pharmacokinetic attributes, Cancer Res., 81 (Supp 4):1-4 … [cited by applicant]
Hodges-Gallagher, L. et al., Development of OP-1250, an Oral Complete Estrogen Receptor Antagonist (CERAN) that Shrinks ER-positive Breast Tumors in Xenograft Models, Olema Therapeutics, presented at the San Antonio Bre… [cited by applicant]
Hodges-Gallagher, L. et al., OP-1250 is a Complete Estrogen Receptor Antagonist (CERAN) that Lacks Agonist Activity on Cell Signaling and Proliferation in Breast Cancer Cells, presented at ENA EORTC NCI AACR 32nd Sympto… [cited by applicant]
Hodges-Gallagher, L. et al., OP-1250, a Complete Estrogen Receptor Antagonist (CERAN) that penetrates the brain and prevents lethality from intracranial xenograft tumors expressing mutant ESR1, presented at AACR #4376 (… [cited by applicant]
Hodges-Gallagher, L. et al., Poster OP-1250: A potent orally available complete antagonist of estrogen receptor-mediated signaling that shrinks wild type and mutant breast tumors, European Journal of Cancer, 138S2: S1-S… [cited by applicant]
Hodges-Gallagher, L. et al., The complete estrogen receptor antagonist (Ceran) OP-1250 shrinks ER+ breast cancer tumors expressing the ESR1-Y537S mutant estrogen receptor in an intracranial xenograft model of brain meta… [cited by applicant]
International Search Report for PCT/US2016/054549, 2 pages (Dec. 9, 2016). [cited by applicant]
International Search Report for PCT/US2020/040863, 4 pages (mailed Oct. 14, 2020). [cited by applicant]
Jeselsohn, R. et al., ESR1 mutations—a mechanism for acquired endocrine resistance in breast cancer, Nat. Rev. Clin. Oncol. 12, 573-583 (2015). [cited by applicant]
Jordan, V. C., Antiestrogens and Selective Estrogen Receptor Modulators as Multifunctional Medicines. 1. Receptor Interactions, J. Med. Chem., 46(6): 883-908 (2003). [cited by applicant]
Jordan, V.C., Alternate antiestrogens and approaches to the prevention of breast cancer, J. Cell Biochem. Suppl., 22:51-7 (1995). [cited by applicant]
Joseph, J.D. et al., The selective estrogen receptor downregulator GDC-0810 is efficacious in diverse models of ER+ breast cancer, Elife, 5. Pii: 15828 (2016). [cited by applicant]
Komm, B. S. and Mirkin, S., An overview of current and emerging SERMs, Journal of Steroid Biochemistry and Molecular Bioglogy, 143: 207-222 (2014). [cited by applicant]
Kumar, V., The estrogen receptor binds tightly to its responsive element as a ligand-induced homodimer, Cell, 55:145-156 (1988). [cited by applicant]
Lai, A. et al, Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts, J. Med Chem., 58(… [cited by applicant]
Laine, M. et al., OP-1250 Prevents Tumor Spread in a Model of Metastatic Mutant ERalpha+ Breast Cancer, presented at American Association for Cancer Research, Apr. 8-13, 2022, New Orleans, LA. [cited by applicant]
Laxmi, Y. R. S et al., Anti-breast cancer potential of SS1020, a novel antiestrogen lacking estrogenic and genotoxic actions, International Journal of Cancer, 127: 1718-1726 (2010). [cited by applicant]
Li, S. et al., Endocrine-Therapy-Resistant ESR1 Variants Revealed by Genomic Characterization of Breast-Cancer-Derived Xenografts, Cell Reports, 4:1116-1130 (2013). [cited by applicant]
Liang, J., Discovery of GNE-149 as a Full Antagonist and Efficient Degrader of Estrogen Receptor alpha for ER+ Breast Cancer, ACS Med. Che. Lett., 11:1342-1347 (2020). [cited by applicant]
Liu, J. et al., Therapeutic utility of natural estrogen receptor beta agonists on ovarian cancer, Oncotarget, 8(3):50002-50014 (2017). [cited by applicant]
Lumachi, F. et al., Treatment of Estrogen Receptor-Positive Breast Cancer, Current Medicinal Chemistry, 20: 596-604 (2013). [cited by applicant]
Mueller, M.D. et al., Regulation of vascular endothelial growth factor (VEGF) gene transcription by estrogen receptors alpha and beta, PNAS, 97(20): 10972-7 (2000). [cited by applicant]
Nardone, A. et al., The oral selective oestrogen receptor degrader (Serd) AZD9496 is comparable to fulvestrant in antagonising ER and circumventing endocrine resistance, BJC, 120:331-339 (2019). [cited by applicant]
Nathan, M. R. and Schmid, P., A Review of Fulvestrant in Breast Cancer, Oncol. Ther., 5:17-29 (2017). [cited by applicant]
Nilsson, S. and Gustafsson, J. A., Estrogen Receptors: Therapies Targeted to Receptor Subtypes, Nature, 89(1):44-55 (2011). [cited by applicant]
Parisian, A. D. et al., Abstract #1618, Poster #P5-08-07, The Complete Estrogen Receptor Antagonist OP-1250 Can Combine with HER2 Inhibition to Inhibit Estrogen Receptor-driven Cellular Proliferation and Shrink Xenograf… [cited by applicant]
Parisian, A. D. et al., Abstract P5-08-07: The complete estrogen receptor antagonist OP-1250 can combine with HER2 inhibition to inhibit estrogen receptor-driven cellular proliferation and shrink xenograft tumors in ER+… [cited by applicant]
Parisian, A. D. et al., Precision Run-on Sequencing (PRO-Seq) Analysis of a Treatment Time Course in ER+ Breast Cancer Cell Lines Profiles the Transcriptional Changes Underlying Response to Complete Estrogen Receptor An… [cited by applicant]
Patel, H. et al., Abstract P6-20-08: Anti-tumor activity of elacestrant (RAD1901) in models harboring ESR1 mutations resistant to standard of care therapies, Cancer Res., 79 (Supp 4):1-4 (2019). [cited by applicant]
Patel, H. K. and Bihani, T., Selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) in cancer treatment, Pharmacology & Therapeutics, 186:1-24 (2018). [cited by applicant]
Patel, M. et al., Abstract P1-17-12: Preliminary data from a phase I/II, multicenter, dose escalation study of OP-1250, an oral CERAN/SERD, in subjects with advanced and/or metastatic estrogen receptor (ER)-positive, HE… [cited by applicant]
Patel, M. et al., Preliminary Data From a Phase 1/2, Multicenter, Dose Escalation Study of OP-1250, an Oral CERAN/SERD, in Patients With Advanced and/or Metastatic Estrogen Receptor (ER)-Positive, HER2-Negative Breast C… [cited by applicant]
Pawlak, K. J. and Wiebe, J. P., Regulation of estrogen receptor (ER) levels in MCF-7 cells by progesterone metabolites, Journal of Steroid Biochem and Mol Biol, 107:172-179 (2007). [cited by applicant]
Pearce, S. and Jordan, V., The biological role of estrogen receptors a and b in cancer, Critical Reviews in Oncology, 50:3-22 (2004). [cited by applicant]
Robertson, J. F. et al., Activity of fulvestrant 500 mg versus anastrozole 1 mg as first-line treatment for advanced breast cancer: results from the FIRST study, J. Clin. Oncol., 27(27):4530-5 (2009). [cited by applicant]
Robertson, J. F. R. et al., Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial, The Lancet, 388:2997-3005 … [cited by applicant]
Rugo, H. S. et al., Endocrine Therapy for Hormone Receptor-Positive Metastatic Breast Cancer: American Society of Clinical Oncology Guideline, Journal of Clinical Oncology, 34:1-37 (2016). [cited by applicant]
Senkus, E. et al., Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Annals of Oncology, 26(Supp5):8-30 (2015). [cited by applicant]
Sharma, A.P. et al., Structure-activity relationship of antiestrogens. Effect of the side chain and its position on the activity of 2,3-diaryl-2H-1-benzopyrans, J. Med. Chem., 33(12):3216-22 (1990). [cited by applicant]
Sharma, A.P. et al, Structure-activity relationship of antiestrogens. Phenolic analogues of 2,3-diaryl-2H-1-benzopyrans, J. Med. Chem., 33(12):3222-9 (1990). [cited by applicant]
Spoerke, J. M. et al., Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant, Nature Communications, 7:11579 (2016). [cited by applicant]
Terry, M., Genentech Quietly Shelves Phase II Cancer Contender, BioSpace, published Apr. 28, 2017 (3 pages). [cited by applicant]
Toy, W. et al., ESR1 ligand binding domain mutations in hormone-resistant breast cancer, Nat Genet., 45(12):1439-1445 (2013). [cited by applicant]
Ullrich, J. W. and Miller, C. P., Estrogen receptor modulator review, Expert Opinion on Therapeutics Patents, 16(5): 559-572 (2006). [cited by applicant]
Veeraraghavan, J. et al., Recurrent ESR1-CCDC170 rearrangements in an aggressive subset of oestrogen receptor-positive breast cancers, Nature Communications, 5:4577 (2014). [cited by applicant]
Verraraghavan, J. et al., Recurrent and pathological gene fusions in breast cancer: current advances in genomic discovery and clinical implications, Breast Cancer Res Treat., 158:219-232 (2016). [cited by applicant]
Vries, E. et al., Abstract P1-10-04: Elacestrant, a novel oral selective estrogen receptor degrader (SERD), decreases tumoral 18F-FES uptake in a phase 1 study of Er+, HER2 −, advanced breast cancer patients, Cancer Res… [cited by applicant]
Wakeling, A.E. et al, A Potent Specific Pure Antiestrogen with Clinical Potential, Cancer Research, 51(15):3867-3873 (1991). [cited by applicant]
Wilson, T. M. et al, 3-[4-(1,2-Diphenylbut-1-enyl)phenyl]acrylic acid: a non-steroidal estrogen with functional selectivity for bone over uterus in rats, J. Med. Chem., 37(11): 1550-2 (1994). [cited by applicant]
Wu, Y.L. et al, Structural basis for an unexpected mode of SERM-mediated ER antagonism, Mol. Cell., 18(14): 413-24 (2005). [cited by applicant]
Clinical Trials, Phase 1b Study in Combination With a CDK4/6 Inhibitor or With a PI3K Inhibitor, History of Changes for Study: NCT05508906, 8 pages (2023). [cited by applicant]
International Search Report for PCT/US2021/021151, 6 pages (mailed Jul. 20, 2021). [cited by applicant]
Roy, D. et al., To Pass or Not To Pass: Predicting the Blood-Brain Barrier Permeability with the 3D-RISM-KH Molecular Solvation Theory, ACS Omega, 4:16774-16780 (2019). [cited by applicant]
Sledge, G. et al., MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2? Advanced Breast Cancer Who Had Progressed While Receiving Endocrine TherapyJournal of Clinical Oncology, 35(25): 2875-288… [cited by applicant]
Weir et al., ‘AZD9496: An Oral Estrogen Receptor Inhibitor That Blocks the Growth of ER-Postive and ESR1-Mutant Breast Tumors in Preclinical Models’, Cancer Research, 76(11):3307-3318 (2016). [cited by applicant]
Dustin, D. et al., ESR1 Mutations in Breast Cancer, Cancer, 125(21):3714-3728 (2019). [cited by applicant]
Kemp, A., Camizestrant demonstrated highly statistically significant and clinically meaningful improvement in progression-free survival in 1st-line advanced HR-positive breast cancer with an emergent ESR1 tumour mutatio… [cited by applicant]