This is a pilot study to determine feasibility and safety of the combination of Dendritic Cell (DC1) vaccines and elacestrant in patients with hormone positive HER2 negative metastatic breast cancer.

Start Date04 Nov 2024

Sponsor / Collaborator

H. Lee Moffitt Cancer Center & Research Institute, Inc.

[+1]

NCT06638307 / RecruitingPhase 1

A Phase 1, First-in-Human Study of MEN2312, a KAT6 Inhibitor, as Monotherapy and in Combination in Participants With Advanced Breast Cancer

This is a first-in-human study of MEN2312, a lysine acetyltransferase 6 (KAT6) inhibitor, in adult participants with advanced breast cancer.

Start Date25 Oct 2024

Sponsor / Collaborator

Stemline Therapeutics, Inc.

NCT06492616 / RecruitingPhase 3

Elacestrant Versus Standard Endocrine Therapy in Women and Men With Node-positive, Estrogen Receptor-positive, HER2-negative, Early Breast Cancer With High Risk of Recurrence-A Global, Multicenter, Randomized, Open-label Phase 3 Study

The primary goal of this study is to evaluate the effectiveness of elacestrant versus standard endocrine therapy in participants with node-positive, Estrogen Receptor-positive (ER+), Human Epidermal Growth Factor-2 negative (HER2-) early breast cancer with high risk of recurrence.

Start Date27 Sep 2024

Sponsor / Collaborator

Stemline Therapeutics, Inc.

100 Clinical Results associated with Elacestrant hydrochloride

100 Translational Medicine associated with Elacestrant hydrochloride

100 Patents (Medical) associated with Elacestrant hydrochloride

Literatures (Medical) associated with Elacestrant hydrochloride

01 Dec 2024·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of non-antiproliferative selective estrogen receptor degraders (SERDs) based on scaffold optimization of elacestrant

Article

Author: Chen, Xuejie ; Liu, Wukun ; Zhao, Zhihao ; Liu, Lijuan ; Wang, Shanglong ; Zheng, Tianpeng ; Lu, Yunlong ; Zhu, Yuqing

Elacestrant, the first oral selective estrogen receptor degrader (SERD), has been approved for ER positive breast cancer in 2023. Recent study showed that elacestrant has moderate pharmacokinetic property and the oral bioavailability is 11 %. In this study, we have performed docking analyses of elacestrant with different cytochrome P450 isoforms. The results indicated that tetrahydronaphthalene scaffold of elacestrant located closely to Heme iron center of P450s and might undergo rapid metabolism by CYP3A4. Therefore, we have changed the tertiary carbon atom to nitrogen atom of the scaffold to attenuate the metabolic effect. The most interesting finding is that compound B16 exhibited significant degradation of ERα at 5 μM but didn't show antiproliferative activity at high concentrations in MCF-7 and T47D cells. Compound B16 may serve as an ER probe to investigate ER status in ER positive breast cancer cells.

15 Nov 2024·ACS Chemical Biology

Pharmacologic Induction of ERα SUMOylation Disrupts Its Chromatin Binding

Article

Author: Wang, Lizhen ; Han, Ting

Estrogen receptor α (ERα)-positive breast cancer patients are typically treated with ERα inhibitors, including selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs). However, the distinct pharmacological properties of various ERα inhibitors remain incompletely understood. In this study, we employed formaldehyde cross-linking followed by ERα immunoprecipitation and mass spectrometry to reveal that fulvestrant, the first FDA-approved SERD, induces the interaction between ERα and SUMO E3 ligases PIAS1 and PIAS2. Biochemical and genomic assays confirmed that fulvestrant induces SUMOylation of ERα, which inhibits ERα's binding to chromatin DNA. In addition, raloxifene (a SERM) and elacestrant (the first FDA-approved oral SERD) were identified as compounds that similarly induce ERα SUMOylation and inhibit its chromatin interaction. Our findings reveal a mechanism by which select ERα inhibitors disrupt ERα function through SUMOylation, offering insights for the development of next-generation ERα-targeted therapies.

01 Nov 2024·CURRENT OPINION IN ONCOLOGY

Endocrine therapy for early breast cancer in the era of oral selective estrogen receptor degraders: challenges and future perspectives

Review

Author: Castellano, Grazia ; Zagami, Paola ; Curigliano, Giuseppe ; Ascione, Liliana

Purpose of review:

Growth and survival of hormone receptor positive breast cancer cells are dependent on circulating hormones (e.g., estrogen and progesterone). Endocrine therapy improved outcomes in both early and advanced hormone receptor positive breast cancer. These treatments include drugs with different mechanisms of action, namely selective estrogen receptor modulators (SERM), aromatase inhibitors, and selective estrogen receptor degraders (SERDs). SERDs represent estrogen receptor antagonists, favoring its degradation and thus interfering with proliferation genes transcription and activation. Fulvestrant is the first approved SERD, administered intramuscularly for treating advanced breast cancer.

Recent findings:

Oral SERDs have been tested to overcome the limitation of the intramuscular administration, and to increase SERD bioavailability. Recently, an oral SERD, Elacestrant, has been approved by the Food and Drug Administration (FDA) for patients carrying an ESR1 mutation. In fact, oral SERDs seem to be effective in tumors harboring ESR1 mutations, a well known mechanism of resistance to endocrine therapy (especially aromatase inhibitors).

Summary:

More recently, oral SERDs have been tested in patients with early hormone receptor positive breast cancer, although their impact on survival and in this curative setting compared to standard endocrine therapy still needs to be elucidated. The best timing and duration of SERD administration and specific biomarkers in (neo)adjuvant setting remain largely unknown.

News (Medical) associated with Elacestrant hydrochloride

26 Nov 2024

·www.prnewswire.com

Menarini Group Presents New and Expanded Data at the 2024 San Antonio Breast Cancer Symposium Reinforcing the Role of ORSERDU® (Elacestrant) for Patients with ER+, HER2- Advanced or Metastatic Breast Cancer (mBC)

Real-world evidence bolsters the efficacy of ORSERDU for the treatment of patients with ER+/HER2- ESR1-mut advanced or mBC. Updated results of elacestrant in combination with abemaciclib show favorable efficacy regardless of the ESR1 mutation status, with a manageable and predictable safety profile in patients with ER+/HER2- mBC. FLORENCE, Italy and NEW YORK, Nov. 26, 2024 /PRNewswire/ -- The Menarini Group ("Menarini"), a leading international pharmaceutical and diagnostics company, and Stemline Therapeutics, Inc. ("Stemline"), a wholly-owned subsidiary of the Menarini Group, focused on bringing transformational oncology treatments to cancer patients, will present new and expanded data on ORSERDU® (elacestrant) at the upcoming 2024 San Antonio Breast Cancer Symposium (SABCS), December 10-13, 2024. Of note, the company will bring real-world progression-free survival (rwPFS) results of ORSERDU in adult patients with ER+/HER2-, advanced or metastatic breast cancer (mBC). Additionally, the company will present updated efficacy results of elacestrant plus abemaciclib, along with a pooled safety analysis from phase 1b/2 of both the ELECTRA and ELEVATE trials. ORSERDU Real-World Progression-Free Survival Data ORSERDU is the first and only oral estrogen receptor antagonist (SERD) approved to target ESR1-mutated tumors, which occur in up to 50% of ER+, HER2- advanced or mBC tumors, as a result of prior exposure to endocrine therapy (ET) in the metastatic setting. Since its approval by the U.S. Food & Drug Administration (FDA) in January 2023, sufficient time has passed to be able to characterize the real-world use of ORSERDU in the current mBC treatment landscape. Results to be reported at SABCS 2024 show the efficacy of ORSERDU in the real-world setting in patients with ER+/HER2- advanced or mBC. The overall population analysis demonstrated median rwPFS of 6.8 months. Median rwPFS for patients with 1-2 lines of prior ET in mBC was 8 months. The rwPFS observed is consistent across the subgroups in the analysis. Updated results and additional information from other patient subgroups will be presented at the congress. The full abstract (SESS-1876) can be viewed here (page 1748). "These exciting data show clinically meaningful real-world progression-free survival with ORSERDU monotherapy," said Virginia Kaklamani, MD, DSc, breast medical oncologist and professor of medicine, UT Health San Antonio, MD Anderson Cancer Center. "As a practicing physician, these results underscore the need to test patients' tumors for the ESR1 mutation at each disease progression using liquid biopsy, so that we can appropriately tailor their treatment and optimize their care." Elacestrant Plus Abemaciclib Combination Study Both the ELEVATE and ELECTRA phase 1b/2 studies were designed with the objective to evaluate patient outcomes through combination treatment options, by overcoming a tumor's resistance to ET. Results to be reported at SABCS 2024 include updated efficacy results from the ELECTRA study which demonstrate favorable progression-free survival (PFS) data. In all efficacy-evaluable patients, median progression-free survival (mPFS) was 8.6 months. In patients with an ESR1 mutation, mPFS was 8.7 months. In patients without an ESR1 mutation, mPFS was 7.2 months. Additionally, a pooled safety analysis of patients from ELECTRA and ELEVATE show a manageable and predictable safety profile in patients with ER+/HER2- mBC that is treated with elacestrant plus abemaciclib, and who previously received one or more lines of prior therapy. Safety was evaluated in all patients who received this combination and was consistent with the known safety profiles of both compounds. The most common all-grade adverse events (AEs) (≥20%) were diarrhea, nausea, neutropenia, vomiting, fatigue, anemia and decreased appetite. No Grade 4 AEs were observed. The full abstract (SESS-1910) can be viewed here (page 3330). "These updated results on the combination of elacestrant plus abemaciclib continue to show encouraging progression-free survival data, and a favorable safety profile, without any new toxicity signals when using these agents in combination," said Hope S. Rugo, MD, Professor of Medicine and Winterhof Family Endowed Professor in Breast Cancer, Director, Breast Oncology and Clinical Trials Education, University of California San Francisco. "Elacestrant continues to show potential to become an endocrine therapy backbone for combination regimens in metastatic breast cancer, and we are excited to explore this treatment combination further as these trials move forward." "It is exciting to see these progression-free survival outcomes in a real-world setting, which shows ORSERDU brings a meaningful benefit for oncologists to offer their patients," said Elcin Barker Ergun, CEO of the Menarini Group. "We are committed to advancing our robust clinical research program on elacestrant and unlocking its full potential, both in monotherapy and combination treatment settings, with the goal of bringing ORSERDU to new patient populations which may benefit." Menarini Stemline will also share results of other relevant data from the Phase 3 EMERALD trial, as well as several trials in progress. Complete List of Menarini Stemline Abstracts: Title: Elacestrant real-world progression-free survival (rwPFS) of adult patients with ER+/HER2-, advanced breast cancer: a retrospective analysis using insurance claims in the United States Poster Number: P3-10-08 Date & Time: Thursday, December 12, 12-2 PM CST Location: TBC Presenting Author: Elyse Swallow Title: Elacestrant plus abemaciclib (abema) combination in patients (pts) with estrogen receptor-positive (ER+), HER2-negative (HER2-) advanced or metastatic breast cancer (mBC) Poster Number: PS7-07 Date & Time: Thursday, December 12, 7-8:30 AM CST Location: TBC Presenting Author: Hope Rugo Title: Elacestrant combination in patients with estrogen receptor-positive (ER+), HER2-negative (HER2-) locally advanced or metastatic breast cancer (mBC): Update from ELEVATE, a phase 1b/2, open-label, umbrella study Poster Number: PS7-06 Date & Time: Thursday, December 12, 7-8:30 AM CST Location: TBC Presenting Author: Hope Rugo Title: Elacestrant vs SOC in ER+, HER2- advanced or metastatic breast cancer (mBC) with ESR1-mutated tumors: ESR1 allelic frequencies and clinical activity from the phase 3 EMERALD trial Poster Number: P1-01-25 Date & Time: Wednesday, December 11, 12-2 PM CST Location: TBC Presenting Author: Aditya Bardia Title: ELEGANT: Elacestrant versus standard endocrine therapy in women and men with node-positive, estrogen receptor-positive, HER2-negative, early breast cancer with high risk of recurrence in a global, multicenter, randomized, open-label phase 3 study Poster Number: P2-08-21 Date & Time: Wednesday, December 11, 5:30-7:30 PM CST Location: TBC Presenting Author: Aditya Bardia Title: ADELA: A randomized, phase 3, double-blind, placebo-controlled trial of elacestrant plus everolimus versus elacestrant in ER+/HER2-advanced breast cancer (aBC) patients with ESR1-mutated tumors progressing on endocrine therapy (ET) plus CDK4/6i Poster Number: P2-10-21 Date & Time: Wednesday, December 11, 5:30-7:30 PM CST Location: TBC Presenting Author: Antonio Llombart-Cussac Title: ELCIN: Elacestrant in women and men with CDK4/6 inhibitor (CDK4/6i)-naïve estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (mBC): An open-label multicenter phase 2 study Poster Number: P2-08-20 Date & Time: Wednesday, December 11, 5:30-7:30 PM CST Location: TBC Presenting Author: Virginia Kaklamani About The Elacestrant Clinical Development Program Elacestrant is also being investigated in several company-sponsored clinical trials in metastatic breast cancer, alone or in combination with other therapies. EMERALD (NCT03778931) is a randomized Phase 3 trial, open label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+, HER2- advanced/metastatic breast cancer patients. ELEVATE (NCT05563220) is a phase 1b/2 clinical trial evaluating the safety and efficacy of elacestrant combined with alpelisib, everolimus, capivasertib, palbociclib, ribociclib or abemaciclib. ELECTRA (NCT05386108) is an open-label phase 1b/2, multicenter study evaluating elacestrant in combination with abemaciclib in patients with ER+, HER2- breast cancer. The phase 2 portion evaluates this treatment regimen in patients with brain metastases. ELCIN (NCT05596409) is a phase 2 trial evaluating the efficacy of elacestrant in patients with ER+, HER2- advanced/metastatic breast cancer who received one or two prior hormonal therapies and no prior CDK4/6 inhibitors in the metastatic setting. ADELA (NCT06382948) is a phase 3 randomized, double-blinded trial evaluating elacestrant in combination with everolimus in patients with ER+, HER2- mBC with ESR1-mut tumors. ELEGANT (NCT06492616) is a phase 3 study evaluating elacestrant versus standard endocrine therapy in women and men with node-positive, estrogen receptor-positive, HER2-negative, early breast cancer with high risk of recurrence. Elacestrant is also being evaluated in additional investigator-led trials, in trials conducted in collaboration with other companies, in metastatic breast cancer as well as in early disease. About ORSERDU (elacestrant) U.S. Indication: ORSERDU (elacestrant), 345 mg tablets, is indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Full prescribing information for the U.S. can be found at . Important Safety Information Warning and Precautions Dyslipidemia: Hypercholesterolemia and hypertriglyceridemia occurred in patients taking ORSERDU at an incidence of 30% and 27%, respectively. The incidence of Grade 3 and 4 hypercholesterolemia and hypertriglyceridemia were 0.9% and 2.2%, respectively. Monitor lipid profile prior to starting and periodically while taking ORSERDU. Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, ORSERDU can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the final dose. Adverse Reactions Serious adverse reactions occurred in 12% of patients who received ORSERDU. Serious adverse reactions in >1% of patients who received ORSERDU were musculoskeletal pain (1.7%) and nausea (1.3%). Fatal adverse reactions occurred in 1.7% of patients who received ORSERDU, including cardiac arrest, septic shock, diverticulitis, and unknown cause (one patient each). The most common adverse reactions (≥10%), including laboratory abnormalities, of ORSERDU were musculoskeletal pain (41%), nausea (35%), increased cholesterol (30%), increased AST (29%), increased triglycerides (27%), fatigue (26%), decreased hemoglobin (26%), vomiting (19%), increased ALT (17%), decreased sodium (16%), increased creatinine (16%), decreased appetite(15%), diarrhea(13%), headache (12%), constipation (12%), abdominal pain (11%), hot flush (11%), and dyspepsia (10%). Drug interactions Concomitant use with CYP3A4 Inducers and/or inhibitors: Avoid concomitant use of strong or moderate CYP3A4 inhibitors with ORSERDU. Avoid concomitant use of strong or moderate CYP3A4 inducers with ORSERDU. Use in specific populations Lactation: Advise lactating women to not breastfeed during treatment with ORSERDU and for 1 week after the last dose. Hepatic Impairment: Avoid use of ORSERDU in patients with severe hepatic impairment (Child-Pugh C). Reduce the dose of ORSERDU in patients with moderate hepatic impairment (Child-Pugh B). The safety and effectiveness of ORSERDU in pediatric patients have not been established. To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or FDA at 1-800-FDA-1088 or . About The Menarini Group The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of $4.7 billion and over 17,000 employees. Menarini is focused on therapeutic areas with high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini's products are available in 140 countries worldwide. For further information, please visit . About Stemline Therapeutics Inc. Stemline Therapeutics, Inc. ("Stemline") a wholly-owned subsidiary of the Menarini Group, is a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics. Stemline commercializes ORSERDU® (elacestrant) in the U.S. and Europe, an oral endocrine therapy indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Stemline also commercializes ELZONRIS® (tagraxofusp-erzs), a novel targeted treatment directed to CD123 for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic cancer, in the United States and Europe, which is the only approved treatment for BPDCN in the U.S. and E.U. to date. Stemline also commercializes NEXPOVIO® (selinexor) in Europe, an XPO1 inhibitor for multiple myeloma. Stemline also has an extensive clinical pipeline of small molecules and biologics in various stages of development for a host of solid and hematologic cancers. Logo: SOURCE Menarini Industrie Farmaceutiche Riunite WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultPhase 3Drug ApprovalPhase 2

09 Sep 2024

·www.businesswire.com

Natera to Present New Signatera™ Colorectal Cancer Data at ESMO Showing 10X Advantage in Overall Survival

AUSTIN, Texas--( BUSINESS WIRE )-- Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and genetic testing, today announced it will present new data on its personalized and tumor-informed molecular residual disease (MRD) test, Signatera, at the 2024 European Society for Medical Oncology (ESMO) Congress taking place Sept. 13-16 in Barcelona, Spain. Natera and its collaborators will present a total of nine abstracts, including five poster presentations from the GALAXY observational arm of the CIRCULATE-Japan trial, one of the largest and most comprehensive prospective studies of MRD testing in resectable colorectal cancer (CRC). The GALAXY data includes an updated analysis of more than 2,100 patients with stage I-IV CRC, reporting 36-month disease-free survival (DFS), and, for the first time, overall survival (OS). Key highlights include: Signatera-positive patients had significantly shorter OS compared to those who were Signatera-negative (hazard ratio of ~10), suggesting that Signatera-negative patients had an almost 10-fold advantage in OS. This compares favorably to all known guideline recommended biomarkers that typically have hazard ratios for overall survival in the 1-4 range. Overall survival stratified by adjuvant chemotherapy (ACT) will also be presented. This will build on prior GALAXY DFS data which has shown significant benefit of ACT in Signatera-positive patients, but lack of benefit in Signatera-negative patients. The current standard of care is based on studies showing that most CRC patients derive a small ~0-5% absolute and ~10-20% relative OS benefit from ACT. Identifying subgroups where this benefit is concentrated is critical for advancing clinical management of early-stage CRC. “ ESMO 2024 will showcase some of our most impactful data in colorectal cancer to-date,” said Minetta Liu, MD, chief medical officer of oncology at Natera. “ Notably, we will present an updated analysis from the GALAXY arm of CIRCULATE-Japan with the first prospective read-out of overall survival based on MRD. These findings underscore the potential for Signatera to predict long-term outcomes.” Other presentations at ESMO will highlight new Signatera data in breast cancer and squamous cell carcinoma of the head and neck. Below is the full list of presentations: Presentation Highlights Poster Presentation #553P | CRC | Sept. 16 | Presenter: Jun Nagata, MD Association of ctDNA-based MRD detection and MRD clearance with short-term overall survival in patients with resectable colorectal cancer: Updated analysis of CIRCULATE-Japan GALAXY Poster Presentation #558P | CRC | Sept. 16 | Presenter: Kozo Kataoka, MD, PhD Survival benefit of adjuvant chemotherapy based on molecular residual disease detection in resected colorectal liver metastases; subgroup analysis from CIRCULATE-Japan GALAXY Oral Presentation and Additional Presentations Oral Presentation | CRC | Presenter: Myriam Chalabi, MD Sept. 15, 09:10 - 09:20 Neoadjuvant immunotherapy in locally advanced MMR-deficient (dMMR) colon cancer (CC): 3-year disease-free survival (DFS) from NICHE-2 Poster Presentation #923P | SCCHN | Sept. 14 | Presenter: Natasha Honoré, MD, PhD Tumor-informed ctDNA assay to predict recurrence in locally advanced SCCHN Poster Presentation #555P | CRC | Sept. 16 | Presenter: Tomoya Harima, MD Association Between Copy Number Aberration and ctDNA MRD in Colorectal Cancer: CIRCULATE-Japan GALAXY Poster Presentation #554P | CRC | Sept. 16 | Presenter: Yoshiaki Nakamura, MD, PhD Novel Clinical Decision Support (CDS) System Optimizing Adjuvant Chemotherapy (ACT) for Colorectal Cancer (CRC) by Integrating Deep Learning and circulating tumor DNA (ctDNA) molecular residual disease (MRD): GALAXY Histotyping Poster Presentation #545P | CRC | Sept. 16 | Presenter: Chiara M. Loeffler, MD HIBRID: Histology and ct-DNA based Risk-stratification with Deep Learning Poster Presentation #338TiP | Breast Cancer | Sept. 16 | Presenter: Michail Ignatiadis, MD, PhD EORTC-2129-BCG: Elacestrant for treating ER+/HER2- breast cancer patients with ctDNA relapse (TREAT ctDNA) Poster Presentation #314P | Breast Cancer | Sept. 16 | Presenter: Mark Magbanua, PhD The impact of changes in tumor mutational landscape during neoadjuvant therapy on tumor-informed ctDNA testing in breast cancer patients About Signatera Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard of care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer, ovarian cancer and muscle invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 70 peer-reviewed papers. About Natera Natera™ is a global leader in cell-free DNA and genetic testing, dedicated to oncology, women’s health, and organ health. We aim to make personalized genetic testing and diagnostics part of the standard of care to protect health, and inform earlier, more targeted interventions that help lead to longer, healthier lives. Natera’s tests are validated by more than 200 peer-reviewed publications that demonstrate high accuracy. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, Texas and San Carlos, California. For more information, visit www.natera.com . Forward-Looking Statements All statements other than statements of historical facts contained in this press release are forward-looking statements and are not a representation that Natera’s plans, estimates, or expectations will be achieved. These forward-looking statements represent Natera’s expectations as of the date of this press release, and Natera disclaims any obligation to update the forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially, including with respect to whether the results of clinical or other studies will support the use of our product offerings, the impact of results of such studies, our expectations of the reliability, accuracy and performance of our tests, or of the benefits of our tests and product offerings to patients, providers and payers. Additional risks and uncertainties are discussed in greater detail in "Risk Factors" in Natera’s recent filings on Forms 10-K and 10-Q and in other filings Natera makes with the SEC from time to time. These documents are available at www.natera.com/investors and www.sec.gov .

Clinical StudyImmunotherapyClinical Result

17 Jul 2024

·pipelinereview.com

Biotheryx Announces First Patient Dosed in Phase 1 Clinical Trial of BTX-9341, a First-in-Class, Dual Bifunctional Degrader of CDK4/6, as a Monotherapy and in Combination

SAN DIEGO, CA, USA I July 17, 2024 I Biotheryx, Inc., a biopharmaceutical company discovering and developing a portfolio of first-in-class protein degraders with a focus on validated targets in cancer and inflammatory diseases, today announced that the first patient has been dosed in its Phase 1 clinical trial evaluating BTX-9341, an investigational oral and bifunctional degrader of cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6), as a monotherapy and in combination with fulvestrant for patients with advanced and/or metastatic hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer who have previously received CDK4/6 inhibitor therapy either in the adjuvant or metastatic setting. “BTX-9341 is a potent and selective CDK4/6 degrader that has shown significant anti-tumor activity in both CDK4/6 inhibitor naïve and resistant preclinical models. We are optimistic that it will meet a critical unmet medical need for patients with HR+/HER2- breast cancer who have received prior CDK4/6 inhibitor therapy,” said Leah Fung, Ph.D., CEO of Biotheryx. “Dosing the first patient in this trial represents a significant milestone for Biotheryx, the patients we aim to serve and the scientists who have made this possible.” The Phase 1 clinical trial will begin with dose escalation of BTX-9341 as a monotherapy, followed by a combination with fulvestrant and will conclude with dose expansion of BTX-9341 in combination with fulvestrant. The trial will assess safety, tolerability, pharmacokinetic and pharmacodynamic activity of BTX-9341 as a monotherapy and in combination with fulvestrant. Once the recommended Phase 2 dose of the combination has been determined, there will be a formal evaluation of efficacy in an expansion cohort. “We are thrilled to have dosed the first patient with BTX-9341 at The START Center for Cancer Research,” stated START Co-Founder and Co-Director of Clinical Research, Dr. Amita Patnaik, MD, FRCPC. “BTX-9341 is a highly novel, first-in-class, potent and selective degrader of CDK4/6, representing an innovative therapeutic approach. It has the potential to transform the care of patients with advanced and/or metastatic HR+/HER2- breast cancer, particularly those who have received prior CDK4/6 inhibitor therapies. This milestone is perfectly aligned with START’s mission to accelerate drug development and provide early access to cutting-edge anticancer therapies, bringing hope to patients and their families.” In preclinical studies, orally administered BTX-9341 demonstrated in vivo CDK4/6 degradation and improved anti-tumor activity as a monotherapy compared to current standard of care treatment regimens. BTX-9341 also demonstrated synergies with selective estrogen receptor degraders including fulvestrant, elacestrant and camizestrant in CDK4/6 naïve and resistant models. About BTX-9341 BTX-9341 is a first-in-class, oral degrader of CDK4/6, important targets for a range of cancers and clinically validated in HR+/HER2- breast cancer. In preclinical breast cancer models, BTX-9341 demonstrated superiority to CDK4/6 inhibitors through potent and highly selective catalytic degradation of CDK4 and CDK6, robust inhibition of Cyclin E and CDK2 transcription, cell cycle arrest and ultimately superior in vivo efficacy in breast cancer xenografts. Beyond this increased efficacy potential, BTX-9341 is differentiated from CDK4/6 inhibitor approaches through the ability to overcome key resistance mechanisms that limit the impact of inhibitors in second line HR+/HER2- breast cancer. About Biotheryx, Inc. Biotheryx is a clinical-stage biopharmaceutical company discovering and developing a portfolio of first-in-class protein degraders, including bifunctional degraders and molecular glues. Our focus is on deploying the differentiated potential of degraders towards validated targets in cancer and inflammatory disease. Members of our founding and scientific teams previously developed the IMiDs, the first U.S. Food and Drug Administration (FDA) approved modulators of Cereblon, the most widely validated E3 ligase involved in protein degradation, and we have applied our expertise in Cereblon binding to build our proprietary PRODEGY platform. Biotheryx’s clinical program, BTX-9341, a bifunctional degrader of CDK4 and CDK6, began a Phase 1 clinical trial in the third quarter of 2024. Biotheryx’s pipeline also includes BTX-10908, a first-in-class degrader of SOS1 for pan-KRAS mutant cancers and PDE4 degraders for inflammatory diseases. For more information, please visit biotheryx.com and engage with us on LinkedIn . SOURCE: Biotheryx

Phase 1PROTACs

100 Deals associated with Elacestrant hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D11671	Elacestrant hydrochloride	-	DB06374

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Advanced breast cancer	GB	Stemline Therapeutics, Inc.	05 Jan 2024
Metastatic breast cancer	GB	Stemline Therapeutics, Inc.	05 Jan 2024
ER-positive/HER2-negative/ ESR1-mutated breast cancer	US	Stemline Therapeutics, Inc.	27 Jan 2023

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Breast Cancer	NDA/BLA	US	Radius Pharmaceuticals, Inc.	22 Jun 2022
Node-positive breast cancer	Phase 3	US	Stemline Therapeutics, Inc.	27 Sep 2024
Estrogen receptor positive breast cancer	Phase 3	BE	A. Menarini Industrie Farmaceutiche Riunite SRL	15 Dec 2023
Estrogen receptor positive breast cancer	Phase 3	FR	A. Menarini Industrie Farmaceutiche Riunite SRL	15 Dec 2023
Estrogen receptor positive breast cancer	Phase 3	DE	A. Menarini Industrie Farmaceutiche Riunite SRL	15 Dec 2023
Estrogen receptor positive breast cancer	Phase 3	IE	A. Menarini Industrie Farmaceutiche Riunite SRL	15 Dec 2023
Estrogen receptor positive breast cancer	Phase 3	IT	A. Menarini Industrie Farmaceutiche Riunite SRL	15 Dec 2023
HER2-negative breast cancer	Phase 3	BE	A. Menarini Industrie Farmaceutiche Riunite SRL	15 Dec 2023
HER2-negative breast cancer	Phase 3	FR	A. Menarini Industrie Farmaceutiche Riunite SRL	15 Dec 2023
HER2-negative breast cancer	Phase 3	DE	A. Menarini Industrie Farmaceutiche Riunite SRL	15 Dec 2023

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


SABCS2024 Manual	Not Applicable	ER-positive/HER2-negative Breast Cancer HER2 Negative	212	Elacestrant	rzohfnngdi(btrfnqgwlv) = wkbrghxecf tpwyzcvghw (ygalysfoqr, 5.4 - NR)	Positive	10 Dec 2024
				Elacestrant (1-2 lines of prior ET)	rzohfnngdi(btrfnqgwlv) = qloevqebpj tpwyzcvghw (ygalysfoqr, 4.9 - NR)
NCT05563220 \| NCT05386108 (ELEVATE, SABCS2024) Manual	Phase 1/2	ER-positive/HER2-negative Breast Cancer HER2 Negative	55	Elacestrant + Abemaciclib (all efficacy-evaluable)	upzdjarkni(jscbfzwvql) = mchbkmluvm zwswstogag (meltmwnizt )	Positive	10 Dec 2024
				Elacestrant + Abemaciclib (ESR1-mut population)	upzdjarkni(jscbfzwvql) = mhuqwpzula zwswstogag (meltmwnizt )
NCT05563220 (ELEVATE, ESMO2024)	Phase 1/2	ER-positive/HER2-negative Breast Cancer ER+ \| HER2-negative \| ESR1-mut	-	Elacestrant + Everolimus	spotdqmdiu(qwjcgowevv) = 10 (43) 2 (9) pojjwvxakl (cajnqnkiyh ) View more	Positive	16 Sep 2024
				Elacestrant + Palbociclib
NCT05563220 (ELEVATE, ASCO2024) Manual	Phase 1/2	ER-positive/HER2-negative Breast Cancer HER2 Positive	20	Elacestrant + Ribociclibribociclib	tfsmfbshaa(yazagcndyg) = Most common (≥30%) all-grade (Gr) AEs were decreased neutrophils/neutropenia (n=6, 50%; Gr3+ n=4, 33%) in the elacestrant (86-172 mg) + ribociclib (400 mg) cohorts zoodkoydia (ityajjwhee ) View more	Positive	24 May 2024
				elacestrantelacestrant (258-345 mg) + palbociclib (100 mg) cohorts
NCT05386108 (ELECTRA, ASCO2024) Manual	Phase 1/2	ER-positive/HER2-negative Breast Cancer Second line ER Positive \| HER2 Negative \| ESR1 Mutation	26	Elacestrant + Abemaciclib	wrjdddbaco(cdvbdjcvvi) = pxtsiifyka brsfjutmaz (dxxayapxiq ) View more	Positive	24 May 2024
EMERALD study (ASCO2024)	Not Applicable	Hormone receptor positive HER2 negative breast cancer ESR1-mutant	418	Elacestrant	dtpbxdfdos(pkhxgfnrvx) = bflllovtfe judyepnbfd (njkciucpiv, 4.2 - not reached [NR]) View more	Positive	24 May 2024
NCT05386108 (ELECTRA, AACR2024)	Phase 1/2	ER-positive/HER2-negative Breast Cancer	-	Elacestrant + Abemaciclib	mptnguwfcq(yufqlybmtf) = fvgrqoddma wjrzjzbdzk (sfmksvdhoi )	-	05 Apr 2024
NCT03778931 (EMERALD, Pubmed \| J Clin Oncol)	Phase 3	ER-positive/HER2-negative Breast Cancer	478	Elacestrant 345 mg	qykiqyqmjg(iqvgroajxo) = More patients who received elacestrant experienced dyslipidemia szfalxkqto (lxdgyixzoa ) View more	Positive	01 Apr 2024
				Investigator's choice of ET
NCT03778931 (EMERALD, CTgov)	Phase 3	ER-positive/HER2-negative Breast Cancer	478	Elacestrant (Elacestrant)	pihnhjzxes(yjtnanybbv) = yhpbqkkngm ihabfsbmjw (dlugytiiwf, qmhphruxrh - bfyqjbcmfw) View more	-	05 Dec 2023
				Standard of Care (Standard of Care (SoC))	pihnhjzxes(yjtnanybbv) = jhdpdyvtfo ihabfsbmjw (dlugytiiwf, cdyyuazkyo - qpjfqmsshy) View more
NCT03778931 (EMERALD, ASCO2023) Manual	Phase 3	ER-positive/HER2-negative/ ESR1-mutated breast cancer ER Positive \| HER2 Negative \| ESR1 wild-type	41	elacestrant (ESR1 non-detected)	lbprqilqlp(olihcchvpc) = dlokodshze qfiffaxtpy (csjxhfyfwn ) View more	Positive	31 May 2023
				Standard of care (ESR1 non-detected)	lbprqilqlp(olihcchvpc) = yoiamskayl qfiffaxtpy (csjxhfyfwn ) View more

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