A Randomized Phase 3, Double-Blind, Placebo-Controlled Study of Elacestrant Plus Everolimus Versus Elacestrant in Patients With ER+/HER2-, ESR1mut Advanced Breast Cancer Progressing to Endocrine Therapy and CDK4/6 Inhibitors

This trial will study a type of advanced breast cancer (ABC) defined as endocrine receptor (ER)-positive/human epidermal growth factor receptor 2(HER2)-negative and estrogen receptor 1 (ESR1)-mutated. Patients will be treated with elacestrant, a compound that acts as a selective estrogen receptor degrader, and everolimus (or placebo), a kinase inhibitor indicated for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer.
The main purpose of the study is to analyze the efficacy (to find out how effective a treatment is) of elacestrant plus everolimus therapy in patients who have ER-positive/HER2-negative, ESR1-mutated, ABC progressing to endocrine therapy and cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. The efficacy of elacestrant plus everolimus combination will be determined by assessing the period from elacestrant plus everolimus (or placebo) treatment initiation until to the first occurrence of disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason, whichever occurs first, defined as progression free survival.
Rigorous eligibility criteria based on specific co-morbidities and clinicopathologic features of their disease have been designed to minimize the risk of patients participating in this study. The anticipated favorable clinical benefits of elacestrant combined with everolimus are projected to outweigh the risks of this treatment. This study will be performed in full compliance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and all applicable local Good Clinical Practice (GCP) and regulations.

Start Date01 Jun 2024

Sponsor / Collaborator

Medica Scientia Innovation Research SL

[+1]

NCT06075953 / RecruitingPhase 2

DCIS: RECAST Trial -Ductal Carcinoma In Situ: Re-Evaluating Conditions for Active Surveillance Suitability as Treatment: a Breast Cancer Prevention Pilot Study

The goal of this trial is to see if active surveillance monitoring and hormonal therapy in patients diagnosed with ductal cell carcinoma in situ (DCIS), an early stage of breast cancer, can be an effective management of the disease.
Participants will be asked to receive control hormonal therapy or an investigational hormonal therapy treatment. Participants will be asked to return for evaluation with MRI at three months and six months. Depending on the evaluation participants will have the option to continue on the treatment. If the evaluation suggests surgery is recommended, the participant will discontinue the study treatment and will undergo surgery. In addition to the treatment and MRI evaluation, participants will be asked to provide blood sample to understand their immune status, provide saliva sample for genetic testing, provide the study with a portion of the tissue or slides generated from tissue removed during surgery performed as part of their standard of care.

Start Date14 Feb 2024

Sponsor / Collaborator

Quantumleap Healthcare Collaborative

NCT05512364 / RecruitingPhase 3

Elacestrant for Treating ER+/HER2- Breast Cancer Patients With ctDNA Relapse

This is an international, multi-center, randomised, open label, superiority phase III trial of elacestrant vs standard endocrine therapy in patients with ER+/HER2- breast cancer and ctDNA relapse.
During the ctDNA screening phase, patients will be tested at different timepoints to detect the presence of ctDNA in their blood.
Patients who are found to be ctDNA-positive and have no evidence of distant metastasis, will be randomised 1:1 between standard endocrine treatment (the same they were receiving when tested ctDNA positive) versus elacestrant, provided they meet all eligibility criteria. After completion of the protocol treatment period, treatment will be left at the discretion of the treating physician.

Start Date15 Dec 2023

Sponsor / Collaborator

Eortc

[+2]

100 Clinical Results associated with Elacestrant

100 Translational Medicine associated with Elacestrant

100 Patents (Medical) associated with Elacestrant

Literatures (Medical) associated with Elacestrant

01 Feb 2024·Current medicinal chemistry

First Approval of Elacestrant as a Selective Estrogen Receptor Degrader for the Treatment of Metastatic Breast Cancer

Article

Author: De, Surya K

Abstract::

Elacestrant was approved by the US FDA on January 27, 2023, for treating postmenopausal women or adult men with estrogen receptor (ER)-positive, HER2- negative, ESR1-mutated advanced or metastatic breast cancer with disease progression prior to using at least one line of endocrine therapy. In this short perspective, physicochemical properties, dosage and administration, mechanism of action, pharmacodynamics, pharmacokinetics, drug interaction, and treatment-related adverse reactions of elacestrant are summarized.

01 Feb 2024·Cancer treatment reviews

Current and emerging treatment approaches for hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer

Review

Author: Marmé, Frederik ; Jhaveri, Komal

In the past decade, significant progress was made in treating hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC), but many clinical questions remain. Cyclin-dependent kinase 4/6 inhibitors are now widely used in combination with endocrine therapy (ET) as standard of care, having demonstrated significant progression-free survival versus ET, and also significant overall survival benefits in the metastatic setting. Inhibition of the PI3K/AKT/mTOR intracellular signaling pathway coupled with ET typically follows first-line therapies. Novel endocrine options including oral selective estrogen receptor down-regulators (SERDs) are in late phases of development, with elacestrant being the first oral SERD to be approved for ESR1-mutant mBC. However, endocrine-refractory disease is inevitable in most patients and represents an area of unmet need, with current recommended options offering poor efficacy, undesirable toxicity, and reduced quality of life. Breakthrough advances in the metastatic setting came via the development of antibody-drug conjugates, which have the advantage of delivering cytotoxic payloads to tumor cells with higher tumor selectivity. Trastuzumab deruxtecan offers a novel therapeutic option for patients with HR+/HER2-low mBC and sacituzumab govitecan is a novel therapeutic option for patients with HR+/HER2- mBC, including those with unmet treatment need in the later-line endocrine-refractory setting. Data gaps still exist regarding optimal sequencing of these novel agents; additional studies into mechanisms of resistance in the metastatic setting would provide further insights. Herein, we describe the current treatment options for HR+/HER2- mBC, including the latest practice-impacting data, and provide commentary on future directions.

01 Jan 2024·JCO oncology practice

Cardiotoxicity of Agents Used in Patients With Breast Cancer

Review

Author: Curigliano, Giuseppe ; Trapani, Dario ; Valenza, Carmine ; Corti, Chiara ; Carey, Lisa Anne ; Nicolò, Eleonora ; Zagami, Paola ; Criscitiello, Carmen

Cancer and cardiovascular diseases are the two major causes of mortality, morbidity, and disability worldwide. The improvement in effective therapeutic options for the management of breast cancer (BC) has led to an increased number of BC survivors, who can experience long-term toxicities from cancer treatments. Adverse events including cardiovascular toxicities must be considered in light of effectiveness of recently approved drugs for BC treatment, including elacestrant, tucatinib, neratinib, olaparib, the immune checkpoint inhibitors, trastuzumab deruxtecan, or sacituzumab govitecan. Many cancer drugs affect the cardiovascular system with a range of clinical manifestations. Prompt diagnosis and treatment as well as a multidisciplinary approach involving a cardio-oncologist is optimal for management of these cardiovascular events.

108

News (Medical) associated with Elacestrant

04 Jun 2024

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GE HealthCare Pharmaco-Economic Study Demonstrates Adding Breast Oncology PET Tracer to Standard Workup of Patients with Metastatic or Recurrent Breast Cancer May Yield Beneficial Clinical and Economic Outcomes, Potentially Saving $142M Over...

Adding a PET/CT scan with [18F]FES, a breast oncology PET tracer, may increase the accuracy of knowing the estrogen receptor (ER) status. This is notable when a tumor sample cannot be obtained, or the risk of a biopsy-related complication is high. Increased diagnostic accuracy may help clinicians select more effective treatments and decrease the rate of re-biopsies, resulting in the potential cost savings of $142M to the US healthcare system over a five-year period,1 according to a new study published in PLOS ONE. The study shows that adding a PET/CT scan with the [18F]FES tracer, commercially available in the US as Cerianna, to biopsy/immunohistochemistry (IHC) may increase the number of true positive and true negative ER status test results by up to eight percentage points2 compared to when biopsy/IHC is used alone. MARLBOROUGH, Mass.--(BUSINESS WIRE)-- GE HealthCare Pharmaco-Economic Study Demonstrates Adding Breast Oncology PET Tracer to Standard Workup of Patients with Metastatic or Recurrent Breast Cancer May Yield Beneficial Clinical and Economic Outcomes, Potentially Saving $142M Over Five Years in the US In a GE HealthCare sponsored pharmaco-economic study published in peer-reviewed journal PLOS ONE, the incidence, prevalence, diagnostic pathways, and treatments of different patients with metastatic or recurrent breast cancer were analyzed using a combination of widely accepted statistical modelling methods to estimate the clinical and associated economic impact of adding a PET/CT scan with [18F]FES, a breast oncology PET tracer, to the current standard diagnostic process. Breast cancer is the most diagnosed cancer worldwide, with approximately 2.3 million new cases appearing in 2020 alone.3 Correct identification of the receptor status in breast cancer is crucial to optimize treatment; however, the diagnostic standard of care which involves biopsy/IHC and imaging, can yield inconclusive results. [18F]FES can be a powerful tool, providing high diagnostic accuracy in detection of estrogen receptor (ER)-positive lesions. The study demonstrated that adding a PET/CT scan with [18F]FES to biopsy/IHC may increase the diagnostic accuracy of the ER status in all appropriate patients with metastatic or recurrent breast cancer. The clinical and economic benefits were especially pronounced in those situations where a tumor sample cannot be obtained, or the risk of a biopsy-related complication is high. Regina Young, Head of Global Market Access in the Pharmaceutical Diagnostics segment of GE HealthCare and lead author of the study said, “We found that if [18F]FES PET/CT was added to the standard diagnostic work up and in line with the Appropriate Use Criteria (AUC) for ER-targeted PET Imaging,4 the increase in diagnostic accuracy could improve the clinical outcomes. Additionally, results suggested a positive correlation between increased diagnostic accuracy, especially when multiple lesions are present,” said Young. "The increase in true ER-positive and ER-negative results may have beneficial clinical and economic outcomes primarily driven by the avoidance of repeated biopsies and futile treatments.” In 2023, FES PET imaging was added to the National Cancer Care Network (NCCN) Clinical Practice Guidelines in Oncology for ER-positive disease under certain circumstances during the systemic staging workup of patients with metastatic and recurrent breast cancer. This inclusion came after the Society of Nuclear Medicine and Molecular Imaging (SNMMI) published its AUC to guide referring and imaging physicians in appropriate use of ER-targeted PET imaging with 16α-18F-fluoro-17ß Fluoroestradiol. According to SNMMI, the inclusion of FES PET in its AUC is intended to help healthcare practitioners provide patients with the best care in a cost-effective manner. The AUC may also enable more efficient approval of FES use by payers.5 GE HealthCare’s Cerianna is the only FDA-approved FES PET imaging agent. Cerianna is indicated for use with PET imaging for the detection of ER-positive lesions as an adjunct to biopsy in patients with metastatic and recurrent breast cancer. Providing a whole-body view of ER-positive lesions, Cerianna may deliver a comprehensive assessment to assist in making an informed diagnosis and individualized treatment plan for the patient. GE HealthCare’s Pharmaceutical Diagnostics segment is a global leader in imaging agents used to support around 119 million procedures per year globally, equivalent to four patient procedures every second. Its Molecular Imaging portfolio combines established proprietary products across cardiology, neurology, and oncology, with an innovative pipeline, all aimed at enabling better-informed diagnosis and monitoring for improved therapy decision-making and clinical outcomes. About GE HealthCare Technologies Inc. GE HealthCare is a leading global medical technology, pharmaceutical diagnostics, and digital solutions innovator, dedicated to providing integrated solutions, services, and data analytics to make hospitals more efficient, clinicians more effective, therapies more precise, and patients healthier and happier. Serving patients and providers for more than 125 years, GE HealthCare is advancing personalized, connected, and compassionate care, while simplifying the patient’s journey across the care pathway. Together our Imaging, Ultrasound, Patient Care Solutions, and Pharmaceutical Diagnostics businesses help improve patient care from diagnosis, to therapy, to monitoring. We are a $19.6 billion business with approximately 51,000 colleagues working to create a world where healthcare has no limits. Follow us on LinkedIn, X (formerly Twitter), Facebook, Instagram, and Insights for the latest news, or visit our website for more information. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. INDICATIONS AND USAGE: CERIANNA is indicated for use with positron emission tomography (PET) imaging for the detection of estrogen receptor (ER)-positive lesions as an adjunct to biopsy in patients with recurrent or metastatic breast cancer. Limitations of Use: Tissue biopsy should be used to confirm recurrence of breast cancer and to verify ER status by pathology. CERIANNA is not useful for imaging other receptors, such as human epidermal growth factor receptor 2 (HER2) and the progesterone receptor (PR). Important Safety Information CONTRAINDICATIONS None. WARNINGS AND PRECAUTIONS Risk of Misdiagnosis Inadequate Tumor Characterization and Other ER-Positive Pathology Breast cancer may be heterogeneous within patients and across time. CERIANNA images ER and is not useful for imaging other receptors such as HER2 and PR. The uptake of fluoroestradiol F 18 is not specific for breast cancer and may occur in a variety of ER-positive tumors that arise outside of the breast, including from the uterus and ovaries. Do not use CERIANNA in lieu of biopsy when biopsy is indicated in patients with recurrent or metastatic breast cancer. False Negative CERIANNA Scan A negative CERIANNA scan does not rule out ER-positive breast cancer. Pathology or clinical characteristics that suggest a patient may benefit from systemic hormone therapy should take precedence over a discordant negative CERIANNA scan. Radiation Risks Diagnostic radiopharmaceuticals, including CERIANNA, expose patients to radiation. Radiation exposure is associated with a dose-dependent increased risk of cancer. Ensure safe drug handling and patient preparation procedures (including adequate hydration and voiding) to protect patients and health care providers from unintentional radiation exposure. Pregnancy Status Assessment of pregnancy status is recommended in females of reproductive potential before administering CERIANNA. ADVERSE REACTIONS In Clinical Trials (n=1207) the most common adverse reactions seen occurred at a rate < 1% were injection-site pain and dysgeusia. USE IN SPECIFIC POPULATIONS Pregnancy Risk Summary All radiopharmaceuticals, including CERIANNA, have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of radiation dose. Advise a pregnant woman of the potential risks of fetal exposure to radiation from administration of CERIANNA. There are no available data on CERIANNA use in pregnant women. No animal reproduction studies using fluoroestradiol F 18 have been conducted to evaluate its effect on female reproduction and embryo-fetal development. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Lactation Risk Summary There are no data on the presence of fluoroestradiol F 18 in human milk, or its effects on the breastfed infant or milk production. Lactation studies have not been conducted in animals. Advise a lactating woman to avoid breastfeeding for 4 hours after CERIANNA administration in order to minimize radiation exposure to a breastfed infant. Pediatric Use The safety and effectiveness of CERIANNA in pediatric patients have not been established. Geriatric Use Clinical studies of fluoroestradiol F 18 injection did not reveal any difference in pharmacokinetics or biodistribution in patients aged 65 and over. DRUG INTERACTIONS Systemic Endocrine Therapies that Bind to ER Drugs that bind to the ER, including SERMs and SERDs, may compete with the binding of fluoroestradiol F18 and may reduce detection of ER-positive lesions with CERIANNA. Before administration of CERIANNA, discontinue drugs that bind to the ER, such as SERMs and SERDs, for at least 5 biological half-lives: (e.g. elacestrant for 11 days, tamoxifen for 8 weeks and fulvestrant for 28 weeks). To report SUSPECTED ADVERSE REACTIONS, contact GE HealthCare at 800 654 0118 (option 2 then option 1) or by email at GPV.drugsafety@gehealthcare.com or FDA at 800 FDA 1088 or 1 Munter-Young R, Fuentes-Alburo A, DiGregorio N, Neeser K, Gultyaev D (2024) Clinical and economic outcomes of adding [18F]FES PET/CT in estrogen receptor status identification in metastatic and recurrent breast cancer in the US. PLoS ONE 19(5): e0302486. 2 Munter-Young, Fuentes-Alburo, DiGregorio, Neeser, Gultyaev, 2024, Table 3 3 Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–49. Epub 20210204. pmid:33538338. 4 Ulaner G, Mankoff D, Clark AS, Fowler AM, Linden HM, Peterson LM, Dehdashti F, Kurland BF, Mortimer J, Mouabbi J, Hyuk Moon D, de Vries EGE (2023) Summary: Appropriate Use Criteria for Estrogen Receptor-Targeted PET Imaging with 16α-F-Fluoro-17β-Fluoroestradiol. The Journal of Nuclear Medicine 64 (3) 351-354. 5 Ulaner G, Mankoff D, Clark AS, Fowler AM, Linden HM, Peterson LM, Dehdashti F, Kurland BF, Mortimer J, Mouabbi J, Hyuk Moon D, de Vries EGE (2023) Summary: Appropriate Use Criteria for Estrogen Receptor-Targeted PET Imaging with 16α-F-Fluoro-17β-Fluoroestradiol. The Journal of Nuclear Medicine 64 (3) 351-354. View source version on businesswire.com: Contacts GE HealthCare Media Contact: Emmy Elguizaoui +1 (978) 243-7503 Emmy.Elguizaoui@gehealthcare.com Source: GE HealthCare View this news release online at:

Radiation Therapy

30 May 2024

·www.biospace.com

Guardant Health to Present Studies at 2024 ASCO Annual Meeting Highlighting Contributions of Its Blood Tests and Real-World Data to Advancing Precision Oncology and Cancer Screening

Studies demonstrate benefits of liquid biopsy and real-world data in targeted therapy selection and therapeutic outcomes in advanced breast cancer Interim data from PICI’s RADIOHEAD study using Guardant Infinity™ platform show correlation between epigenomic biomarkers and patient response to immunotherapy treatment across more than 13 cancer types PALO ALTO, Calif.--(BUSINESS WIRE)-- Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, today announced the company and its research collaborators will present data from 16 studies highlighting the role of Guardant blood tests and real-world data in advancing precision oncology and cancer screening at the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting, May 31-June 4 in Chicago. Featured presentations will share data supporting the utility of therapy response monitoring with circulating tumor DNA (ctDNA) using Guardant Infinity and the use of the GuardantINFORM™ clinical-genomic database to characterize drivers and resistance mechanisms and their association with real-world outcomes in a variety of solid tumor types. Additional studies will present data supporting the application of genomic and epigenomic biomarkers in areas such as minimal residual disease detection and cohort characterization. “The robust data we present at ASCO will further demonstrate the important scientific and clinical developments in cancer care that are possible using liquid biopsy,” said Helmy Eltoukhy, Guardant Health chairman and co-CEO. “Several studies will highlight the tremendous potential of epigenomic analysis using our Guardant Infinity platform to quantify tumor fraction and characterize therapy resistance mechanisms in order to improve treatment response across multiple cancer types.” Featured presentations include: An oral presentation of a study using the Guardant360® liquid biopsy and exploring racial differences in genomic profiles and targeted treatment use in ER+ HER2- metastatic breast cancer (Abstract 1017, Monday, June 3, 11:30 am – 1:00 pm, Hall D1) Interim data readout from the collaboration between Guardant Health and the Parker Institute for Cancer Immunotherapy (PICI) to identify genomic and epigenomic biomarkers using Guardant Infinity for quantification of tumor fraction and association with outcomes from the RADIOHEAD real-world advanced pan-cancer cohort (Abstract 2570, Saturday, June 1, 9:00 am – 12:00 pm, Hall A) Complete list of Guardant Health and collaborator presentations at ASCO Abstract Title (Hall A unless otherwise noted) Product Saturday, June 1 | 9:00 am – 12:00 pm 2570 Use of a tissue-free epigenomic circulating tumor DNA (ctDNA) assay for quantification of tumor fraction (TF) and association with outcomes from RADIOHEAD real-world advanced pan-cancer cohort Guardant Infinity 3041 Association of KRAS G12D vs. G12V circulating tumor DNA variant allele fraction and real-world overall survival in metastatic non-small cell lung and colorectal cancers Guardant Infinity Saturday, June 1 | 1:30 pm – 4:30 pm LBA3557 A randomized study evaluating tailoring of advanced/metastatic colorectal cancer (mCRC) therapy using circulating tumor DNA (ctDNA): TACT-D Guardant360 CDx 3519 Candidate molecular alterations associated with potential resistance in KRAS G12D gastrointestinal cancers Guardant360 & Guardant360/CDx 3602 Characteristics of patients (pts) with disease relapse despite absence of molecular residual disease (MRD) after resection of colorectal oligometastases (CRM): implications from PRECISION study Guardant360 & Guardant Reveal™ 3545 Characterization of mutational signatures demonstrating adaptive mutability post anti-EGFR therapy in a real-world metastatic colorectal cancer cohort GuardantINFORM Sunday, June 2 | 9:00 am – 12:00 pm 1037 Molecular profiling of serial liquid biopsy specimens utilizing cell free DNA (cfDNA) and circulating tumor cells (CTCs) in TBCRC041: A phase II study of alisertib in endocrine resistant metastatic breast cancer (MBC) Guardant Infinity 1043 Evaluating metrics of circulating tumor DNA response and progression using a high sensitivity tumor-agnostic assay in metastatic HR+/HER2- breast cancer receiving endocrine therapy and a CDK4/6-inhibitor Guardant Infinity 1071 Real-world (RW) elacestrant use patterns and therapeutic outcomes in patients (pts) with hormone receptor-positive (HR+)/HER2-negative advanced breast cancer (aBC) GuardantINFORM 5069 Dynamic androgen receptor alterations (ARa) ctDNA profiles and clinical outcomes in metastatic prostate cancer (mPC) GuardantINFORM Monday, June 3 | 9:00 am – 12:00 pm | Hall A 5592 Serial circulating tumor DNA (ctDNA) sequencing to monitor response and define acquired resistance to letrozole/abemaciclib in endometrial cancer (EC) Guardant Infinity Monday, June 3 | 11:30 am – 1:00 pm | Hall D1 1017 Rapid Oral Abstract Session: Racial differences in genomic profiles and targeted treatment use in ER+ HER2- metastatic breast cancer Guardant360 Online only e13097 Co-occurrence of ESR1 and PIK3CA mutations in HR+/HER2- metastatic breast cancer: Incidence and outcomes with targeted therapy Guardant360 & Guardant360 CDx e12566 Molecular profiling in ABC: Is complementary testing with tissue and plasma necessary and clinically relevant? Guardant360 e13702 Utilization of circulating tumor DNA (ctDNA) testing by race and ethnicity in more than 135,000 patients GuardantINFORM e20088 Use of cell-free tumor DNA in early detection of lung cancer Shield™ (next generation) The full abstracts for Guardant Health and a list of all abstracts being presented at the meeting can be found at the ASCO website. For more information and updates from the meeting, follow Guardant Health on LinkedIn and X (Twitter) or visit ASCO booth #28115. About Guardant Health Guardant Health is a leading precision oncology company focused on guarding wellness and giving every person more time free from cancer. Founded in 2012, Guardant is transforming patient care by providing critical insights into what drives disease through its advanced blood and tissue tests, real-world data and AI analytics. Guardant tests help improve outcomes across all stages of care, including screening to find cancer early, monitoring for recurrence in early-stage cancer, and helping doctors select the best treatment for patients with advanced cancer. For more information, visit guardanthealth.com and follow the company on LinkedIn, X (Twitter) and Facebook. Forward-Looking Statements This press release contains forward-looking statements within the meaning of federal securities laws, including statements regarding the potential utilities, values, benefits and advantages of Guardant Health’s liquid biopsy tests or assays, which involve risks and uncertainties that could cause the actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are based on current expectations, forecasts and assumptions, and actual outcomes and results could differ materially from these statements due to a number of factors. These and additional risks and uncertainties that could affect Guardant Health’s financial and operating results and cause actual results to differ materially from those indicated by the forward-looking statements made in this press release include those discussed under the captions “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operation” and elsewhere in its Annual Report on Form 10-K for the year ended December 31, 2023, and in its other reports filed with or furnished to the Securities and Exchange Commission thereafter. The forward-looking statements in this press release are based on information available to Guardant Health as of the date hereof, and Guardant Health disclaims any obligation to update any forward-looking statements provided to reflect any change in its expectations or any change in events, conditions, or circumstances on which any such statement is based, except as required by law. These forward-looking statements should not be relied upon as representing Guardant Health’s views as of any date subsequent to the date of this press release.

ASCOImmunotherapyPhase 2

23 May 2024

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Menarini Group Presents Updated Data from ELECTRA and ELEVATE Combination Studies of Elacestrant (ORSERDU®) in Patients with ER+, HER2- Metastatic Breast Cancer (mBC) at the ASCO 2024 Annual Meeting

The ELECTRA and ELEVATE studies were designed to overcome different resistance mechanisms and improve patient outcomes with oral-oral combination options. Updated results from the ELECTRA study, evaluating elacestrant in combination with abemaciclib regardless of metastatic site, show a safety pro with previous results. Recommended phase 2 dose for this combination is presented. Updated analysis from the ELEVATE study demonstrates that all evaluable elacestrant plus targeted therapy combination arms are consistent with the known safety profiles of everolimus, alpelisib, ribociclib and palbociclib plus standard of care endocrine therapy. Recommended phase 2 dose for the combination of elacestrant and everolimus is presented. FLORENCE, Italy & NEW YORK--(BUSINESS WIRE)-- 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 updated results from phase 1b/2 ELECTRA and ELEVATE clinical studies evaluating elacestrant (ORSERDU®) in combination with other treatments. Both the ELECTRA and ELEVATE studies were designed to overcome different resistance mechanisms observed in estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (mBC) and improve patient outcomes through novel oral-oral combination treatment options. Data will be presented at the 2024 American Society of Clinical Oncology (ASCO), on June 2 from 9 a.m. to 12 p.m. CT. This press release features multimedia. View the full release here: The ELECTRA study is evaluating elacestrant in combination with abemaciclib in patients with ER+, HER2- metastatic breast cancer with brain metastases; however, the phase 1b portion of this study was conducted in all metastatic sites, including brain metastases. The updated phase 1b results continue to show a satisfactory safety profile, consistent with prior findings, and promising activity in patients with ER+, HER2- advanced or mBC regardless of metastatic site. Based on the results of this portion of the study, the recommended phase 2 dose (RP2D) will be reported as part of the data presentation. Currently, the phase 2 portion of ELECTRA is ongoing at the RP2D to further characterize the efficacy and safety in patients with ER+, HER2- metastatic breast cancer with brain metastases, since both elacestrant and abemaciclib cross the blood-brain barrier. “It is encouraging to see that, even in the early stages of the trial, the combination of elacestrant plus abemaciclib indicates a tolerable and manageable safety pro the patients in the clinical trial,” said Erika Hamilton, MD, Director of Breast Cancer Research and Executive Chair of the Breast Cancer Research Executive Committee for Sarah Cannon Research Institute. “The study continues to demonstrate elacestrant’s potential in combination with other therapies and we look forward to analyzing more data from this combination for this patient population in need of new options.” The ELEVATE study is evaluating elacestrant in combination with CDK4/6 inhibitors (palbociclib, abemaciclib and ribociclib) and with inhibitors of the PI3K/AKT/mTOR pathway (everolimus, alpelisib and capivasertib). The updated Phase 1b results show that the combinations evaluated are consistent with the known safety profiles of each targeted therapy plus standard of care endocrine therapy. Based on the results of this portion of the study, the RP2D will be reported for elacestrant in combination with everolimus. Additional cohorts, including elacestrant plus capivasertib, are currently under evaluation to further characterize the safety, assess efficacy and determine the RP2D for each combination arm. Phase 2 for the combination of elacestrant and abemaciclib in ER+, HER2- metastatic breast cancer, irrespective of the metastatic site, is already ongoing. “As we evaluate the various combinations of elacestrant plus CDK4/6 and PI3K/AKT/mTOR inhibitors, we continue to see consistent and manageable safety findings across all arms of the trial, and so far, elacestrant does not appear to add any incremental toxicity to the combination regimens in which it is being studied,” 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. “These data build on our understanding of elacestrant’s role in metastatic breast cancer and reinforce its potential as an endocrine therapy backbone in combination regimens.” “Since its approval in 2023, ORSERDU has had a meaningful impact as an endocrine therapy for people who are living with ER+, HER2- metastatic breast cancer harboring ESR1 mutations,” said Elcin Barker Ergun, CEO of the Menarini Group. “The data we are presenting at ASCO highlight elacestrant’s potential to further enhance patient outcomes when combined with other compounds.” About The Elacestrant Clinical Development Program Elacestrant is also being investigated in several company-sponsored clinical trials in metastatic breast cancer disease, alone or in combination with other therapies. 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. 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 pro 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. View source version on businesswire.com: Contacts Media The Menarini Group Valeria Speroni Cardi Email: pressoffice@menarini.com Stemline Therapeutics, Inc. Cheya Pope Email: media@menarinistemline.com Source: The Menarini Group View this news release online at:

Phase 2Drug ApprovalASCOPhase 1Phase 3

100 Deals associated with Elacestrant

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KEGG	Wiki	ATC	Drug Bank
D11671	Elacestrant	-	DB06374

R&D Status

Approved

10 top approved records.

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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
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
HER2-negative breast cancer	Phase 3	IE	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


NCT05386108 (ELECTRA, ASCO2024) Manual	Phase 1/2	ER-positive/HER2-negative Breast Cancer Second line HER2 Negative \| ER Positive \| ESR1 Mutation	26	Elacestrant + Abemaciclib	xrilicfuhv(jshjltyyxq) = qiuoousdgx tnbdsjmmrm (sxtovlijzz ) View more	Positive	24 May 2024
NCT05563220 (ELEVATE, ASCO2024)	Phase 1/2	ER-positive/HER2-negative Breast Cancer ESR1-mut	-	Elacestrant + Ribociclib	aiqacpehan(zwtzrvneum) = 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 cqyqgfiscs (sgxizftjzp ) View more	Positive	24 May 2024
EMERALD study (ASCO2024)	Not Applicable	Hormone receptor positive HER2 negative breast cancer ESR1-mutant	418	Elacestrant	qzkcdqpojb(hggizlacvv) = uzolngetue mwjpakdwgu (dabmqsjrra, 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	xwprlhcofv(jujwrcrdfr) = sifufygrhy yadekhupjl (ubrnvjaoly )	-	05 Apr 2024
NCT03778931 (EMERALD, CTgov)	Phase 3	ER-positive/HER2-negative Breast Cancer	478	Elacestrant (Elacestrant)	rnttoyrovb(sjqgbruebv) = xpuzaqikte wtwbweaahp (jzcizykbin, zbspkhxtsd - rewenahlvq) View more	-	05 Dec 2023
				Standard of Care (Standard of Care (SoC))	rnttoyrovb(sjqgbruebv) = vbyqiyzdma wtwbweaahp (jzcizykbin, adbbsfnbti - yzbkrjsezs) 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)	nnrnwlschr(bhbzepxgkf) = qrracbmipm yioigikomh (oqyezerkwg ) View more	Positive	31 May 2023
				Standard of care (ESR1 non-detected)	nnrnwlschr(bhbzepxgkf) = lbxbszuwws yioigikomh (oqyezerkwg ) View more
NCT03778931 (EMERALD, ESMO_BC2023)	Phase 3	Metastatic breast cancer ER+ \| HER2− \| CDK4/6i ... View more	478	Elacestrant	dtdrxrpaor(txskptpnjj) = numerically better outcomes ktnqvxtjnp (pdpzyafihv ) View more	Positive	11 May 2023
				Standard of care endocrine therapy
NCT03778931 (EMERALD, AACR2023) Manual	Phase 3	Hormone receptor positive breast cancer HR positive	-	elacestrant	vqgiilazzz(aeqrzhcldx) = Post-hoc analysis of the EMERALD clinical trial confirms that elacestrant is effective in patient populations previously treated with fulvestrant-containing regimens, irrespective of ESR1 mutation status reknjbvkly (vmsmljxrwo )	Positive	14 Apr 2023
NCT03778931 (EMERALD, FDA) Manual	Phase 3	ER-positive/HER2-negative/ ESR1-mutated breast cancer Second line ER+ \| HER2- \| ESR1 mutations	228	ORSERDU 345 mg	spsyzylqnt(cantamqqvj) = wjjnjdgzko jsnwczfcms (naimouibpj, 2.2 - 7.3) View more	Superior	27 Jan 2023
				Fulvestrant or an Aromatase Inhibitor	spsyzylqnt(cantamqqvj) = hftgzbfuid jsnwczfcms (naimouibpj, 1.9 - 2.1) View more
NCT03778931 (EMERALD, ASCO2022) Manual	Phase 3	ER-positive/HER2-negative Breast Cancer Second line ER Positive \| HER2 Negative	477	elacestrant (patients without prior chemotherapy)	ccdtdndlms(bajujxhxet) = ddxeeoeiua owjrdimtfc (jtwlbteish ) View more	Positive	02 Jun 2022
				investigator’s choice of fulvestrant or aromatase inhibitor (patients without prior chemotherapy)	ccdtdndlms(bajujxhxet) = dvkkxdhfke owjrdimtfc (jtwlbteish ) View more

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