Elacestrant for Breast Cancer

(ELEGANT Trial)

Recruiting at 585 trial locations

Overseen By Stemline Trials

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Stemline Therapeutics, Inc.

Must be taking: Endocrine therapy

Disqualifiers: Inflammatory breast cancer, prior malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 years

4220 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how well the new drug elacestrant (also known as Orserdu) performs compared to standard hormone treatments for individuals with a specific type of early breast cancer. The focus is on those with Estrogen Receptor-positive and HER2-negative breast cancer at high risk of recurrence. Participants will either take elacestrant or continue their current standard hormone therapy. This trial suits those who have been on hormone therapy for 2 to 5 years and face a high risk of cancer returning. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you must stop taking your current medications. However, you must have completed or discontinued any prior CDK4/6 or PARP inhibitors before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that elacestrant is generally well-tolerated. The most common side effects include nausea, tiredness, vomiting, and diarrhea. These side effects are typical for many cancer treatments and can usually be managed.

Further research indicates that elacestrant can be safely used with other cancer drugs without increasing the risk of additional side effects. This allows it to be combined with other treatments without causing extra problems.

In summary, while elacestrant does have some common side effects, current research considers it safe. This information comes from studies involving people with similar types of breast cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Elacestrant is unique because it represents a novel approach to treating breast cancer by specifically targeting the estrogen receptor. Unlike traditional endocrine therapies like aromatase inhibitors (such as anastrozole, letrozole, and exemestane) or tamoxifen, which broadly reduce estrogen effects or levels, elacestrant is a selective estrogen receptor degrader (SERD). This means it not only blocks the receptor but also leads to its degradation, potentially making it more effective against tumors that have become resistant to other endocrine therapies. Researchers are excited about elacestrant because it offers a promising new option for patients with advanced breast cancer, potentially improving outcomes for those who have limited responses to current treatments.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Research shows that elacestrant, which participants in this trial may receive, has promising results for treating certain types of breast cancer. In earlier studies, patients taking elacestrant experienced a progression-free survival (PFS) of about 5 to 7 months. PFS refers to the time during and after treatment when the cancer does not worsen. This duration was longer than with other treatments like fulvestrant, which had a PFS of only 2 months. Elacestrant also slowed cancer growth more effectively in patients with specific genetic mutations. Overall, these findings suggest that elacestrant could be an effective option for treating estrogen receptor-positive, HER2-negative breast cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Medical Director

Principal Investigator

Stemline Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for men and women with ER+, HER2- early breast cancer at high risk of recurrence. They must have completed 24 to 60 months of endocrine therapy, such as AIs or tamoxifen, possibly with a CDK4/6 inhibitor but not currently on it. Participants should not have any evidence of cancer recurrence or distant metastases.

Inclusion Criteria

I was initially considered at high risk of my cancer coming back.

My breast cancer is ER-positive, HER2-negative, and has not spread or come back.

I have been on hormone therapy for 2-5 years, possibly with a CDK4/6 inhibitor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either elacestrant or standard endocrine therapy for 5 years

5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Elacestrant

Trial Overview The study compares the effectiveness of elacestrant against standard endocrine therapies like anastrozole, letrozole, exemestane, and tamoxifen in preventing breast cancer from coming back.

How Is the Trial Designed?

Group I: Standard of Care (SoC) Endocrine Therapy Experimental Treatment 4 Interventions

Participants will receive the SoC endocrine therapy that was used prior to randomization: * AI (anastrozole 1 mg QD, letrozole 2.5 mg QD, or exemestane 25 mg QD); or * Tamoxifen 20 mg QD

Group II: Elacestrant Experimental Treatment 1 Intervention

Participants will receive 345 milligrams (mg) elacestrant once daily (QD) for 5 years.

Elacestrant is already approved in United States, European Union for the following indications:

Approved in United States as Orserdu for:

• ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer

Approved in European Union as Orserdu for:

• ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer

Who Is Running the Clinical Trial?

Stemline Therapeutics, Inc.

Lead Sponsor

Trials

24

Recruited

6,500+

Stemline Therapeutics, Inc.

Lead Sponsor

Trials

24

Recruited

6,500+

Published Research Related to This Trial

Elacestrant (ORSERDU™) is a newly approved oral medication for treating advanced or metastatic breast cancer in postmenopausal women and adult men with specific estrogen receptor mutations, following at least one line of endocrine therapy.

The drug specifically targets estrogen receptor-positive, HER2-negative breast cancer, and its approval in the USA marks a significant milestone in its development, with ongoing regulatory assessments in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant: First Approval. Hoy, SM.[2023]

Elacestrant was approved by the FDA for treating advanced or metastatic breast cancer in postmenopausal women and adult men with specific estrogen receptor mutations, highlighting its targeted approach for patients who have not responded to prior endocrine therapy.

The summary includes important details about elacestrant's mechanism of action and safety profile, which are crucial for understanding its role in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Approval of Elacestrant as a Selective Estrogen Receptor Degrader for the Treatment of Metastatic Breast Cancer. De, SK.[2023]

In a phase III trial involving 477 patients with ER-positive/HER2-negative advanced breast cancer, elacestrant significantly improved progression-free survival (PFS) compared to standard-of-care endocrine therapy, with a hazard ratio of 0.70 for all patients and 0.55 for those with ESR1 mutations.

While elacestrant showed promising efficacy, it was associated with a higher rate of treatment-related adverse events, including nausea, and a greater percentage of patients discontinuing treatment due to side effects compared to standard therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. Bidard, FC., Kaklamani, VG., Neven, P., et al.[2023]

Elacestrant is the first oral selective estrogen receptor degrader (SERD) approved by the FDA for treating ER/PR-positive, HER2-negative metastatic breast cancer with ESR1 mutations, showing improved median progression-free survival compared to standard endocrine therapy in the EMERALD trial.

The drug acts as a mixed ER agonist/antagonist and has specific metabolic considerations, being primarily processed by CYP3A4, which can lead to drug interactions; dose adjustments are recommended for patients with moderate hepatic dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology and pharmacokinetics of elacestrant. Beumer, JH., Foldi, J.[2023]

The phase I trial assessed the safety and efficacy of elacestrant, a selective estrogen receptor degrader, specifically in patients with breast cancer.

This study represents an important step in evaluating new treatment options for breast cancer, focusing on a novel mechanism of action that targets estrogen receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Signs of Response to Elacestrant Seen in ER+ HER2- Breast Cancer. [2021]

Elacestrant, a selective estrogen receptor degrader, was found to be safe and well tolerated in a study involving 140 postmenopausal women, with doses up to 1000 mg daily not reaching the maximum tolerated dose.

The drug showed good oral bioavailability and a half-life of 27 to 47 hours, allowing for once-daily dosing, while effectively engaging estrogen receptors and demonstrating some ability to cross the blood-brain barrier.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and Pharmacodynamic Studies of Elacestrant, A Novel Oral Selective Estrogen Receptor Degrader, in Healthy Post-Menopausal Women. Conlan, MG., de Vries, EFJ., Glaudemans, A., et al.[2021]

Elacestrant (RAD1901) effectively degrades estrogen receptors and inhibits the growth of estrogen receptor-positive (ER+) breast cancer cells in both laboratory and patient-derived models, showing significant antitumor activity.

The combination of elacestrant with other therapies like palbociclib or everolimus enhances its efficacy, suggesting it could be a valuable treatment option for patients with ER+ breast cancer, including those with resistant mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant (RAD1901), a Selective Estrogen Receptor Degrader (SERD), Has Antitumor Activity in Multiple ER+ Breast Cancer Patient-derived Xenograft Models. Bihani, T., Patel, HK., Arlt, H., et al.[2018]

Elacestrant (RAD-1901) is a selective estrogen receptor degrader that was approved by the USFDA for treating ER+ HER2-positive breast cancer, demonstrating anticancer activity in both laboratory and animal models.

The review discusses Elacestrant's development, including its medicinal chemistry, mechanism of action, and safety profile based on clinical trial data, highlighting its potential as an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant: a new FDA-approved SERD for the treatment of breast cancer. Bhatia, N., Thareja, S.[2023]

Elacestrant, an oral selective estrogen receptor downregulator, was approved by the FDA in January 2023 for treating hormone receptor positive (HR+) HER2- advanced breast cancer, showing improved progression-free survival in patients with ESR1 mutations who had previously failed treatment with CDK 4/6 inhibitors and endocrine therapy.

Clinical trials indicate that elacestrant has a safety profile comparable to existing endocrine therapies and provides an effective alternative treatment option, especially for patients who have not responded to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant for ER-Positive HER2-Negative Advanced Breast Cancer. Hageman, E., Lussier, ME.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11847623/

Elacestrant in hormone receptor-positive metastatic breast ... Despite its effectiveness, fulvestrant is associated with a relatively low median progression-free survival (PFS) of just 2 months. Additionally ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.1071

Real-world (RW) elacestrant use patterns and therapeutic ... Results: 418 aBC pts were treated with elacestrant, with a median age of 62 years. Elacestrant was used across metastatic LOT (2nd: 12%, 3rd: 18 ...

3. targetedonc.com targetedonc.com/view/real-world-data-reveal-longer-pfs-with-elacestrant-in-breast-cancer

Real-World Data Reveal Longer PFS With Elacestrant in ... Wander acknowledges the lack of uniform scans, but despite these limitations, elacestrant performed well, with PFS estimates of 5 to 7 months.

4. orserduhcp.com orserduhcp.com/efficacy/

EMERALD Trial Primary Endpoint & Efficacy - orserdu Efficacy · Number of PFS events: 62 (54%) with ORSERDU vs 78 (69%) with fulvestrant or AI · A statistically significant PFS was observed in the ITT population and ...

5. esmoopen.com esmoopen.com/article/S2059-7029(24)01470-4/fulltext

Elacestrant in ESR1-mutant, endocrine-responsive ... Compared with the control arm, elacestrant therapy was associated with more grade 1-2 toxicity, including nausea (35% versus 19%) and vomiting ( ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11895172/

Post-marketing safety of elacestrant in breast cancer FDA data analysis revealed that the most commonly reported elacestrant-related AEs were nausea, fatigue, disease progression, vomiting, diarrhea ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.1079

Elacestrant combinations in patients (pts) with ER+/HER2- ... Elacestrant combinations continue to demonstrate safety consistent with the known profiles of each drug + SOC ET without increased risk of associated AEs.

8. menarini.com menarini.com/en-us/news/news-detail/menarini-group-presents-updated-data-underscoring-the-combinability-of-elacestrant-orserdu174-in-patients-with-er-her2-metastatic-breast-cancer-mbc-at-the-asco-2025-annual-meeting.html

Metastatic Breast Cancer (mBC) at the ASCO 2025 Annual ... Preliminary efficacy analysis from the elacestrant plus everolimus and ribociclib cohorts of the ELEVATE study, along with updated safety data ...

9. onclive.com onclive.com/view/elacestrant-shows-tolerability-in-combination-with-cdk4-6-pi3k-inhibitors-in-advanced-er-breast-cancer

Elacestrant Shows Tolerability in Combination With CDK4/ ... Elacestrant demonstrated tolerability with multiple targeted agents in ER-positive, HER2-negative advanced breast cancer, showing potential as ...

10. karger.com karger.com/brc/article/20/5/348/928323/Evaluation-of-Safety-of-Elacestrant-in-Patients

Evaluation of Safety of Elacestrant in Patients with Breast ... Common AEs include nausea, vomiting, musculoskeletal pain, elevated blood cholesterol, and fatigue [19]. The current safety information for ...