Elacestrant Combinations for Breast Cancer

(ELEVATE Trial)

Recruiting at 107 trial locations

Overseen By Stemline Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Stemline Therapeutics, Inc.

Must be taking: LHRH agonists

Must not be taking: CYP3A4 inducers, inhibitors

Disqualifiers: CNS metastases, Visceral spread, BRCA mutation, others

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

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

Compensation: Varies

Number of Visits: Unknown

435 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and assess the safety of elacestrant (Orserdu) when combined with other treatments for advanced breast cancer that is estrogen receptor positive and HER2 negative. The study will explore various drug combinations to identify the most effective and safe options. Individuals whose breast cancer has progressed despite treatment and who have at least one measurable tumor may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking certain medications before starting, such as anti-cancer therapies, strong or moderate inducers or inhibitors of a specific liver enzyme (CYP3A4), and certain herbal preparations. There is a 'washout' period (time without taking these medications) of 14 days or 5 half-lives, whichever is shorter, before the first dose of trial therapy.

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

Research has shown that elacestrant, when combined with other drugs, generally maintains a safety profile similar to other breast cancer treatments. For instance, studies combining elacestrant with drugs like everolimus and ribociclib have demonstrated that the safety aligns with known profiles of each drug, without an increased risk of side effects.

The FDA has approved elacestrant alone for treating certain types of breast cancer, supporting its safety for use in patients. It has been tested in many patients with advanced breast cancer, and its side effects are similar to those of other hormone-related therapies.

In other combinations being tested, such as elacestrant with alpelisib or palbociclib, early results indicate that these combinations are tolerable for patients, meaning patients can manage the side effects without major issues.

Although studies are ongoing, evidence suggests that elacestrant and its combinations have a manageable safety profile, indicating they are generally safe and well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about elacestrant combinations for breast cancer because they offer a novel approach compared to standard treatments like hormone therapies and CDK4/6 inhibitors. Elacestrant is a selective estrogen receptor degrader (SERD), which means it targets and breaks down estrogen receptors, potentially overcoming resistance seen with other hormone therapies. When combined with drugs like capivasertib, alpelisib, or ribociclib, these treatments could enhance effectiveness by simultaneously targeting multiple pathways involved in cancer growth. This multi-pronged strategy may provide a promising new option for patients, especially those who haven't responded well to existing therapies.

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

Research shows that elacestrant may effectively treat a type of advanced breast cancer known as ER+/HER2-. In this trial, participants will receive different combinations of elacestrant with other drugs. One arm will test elacestrant with capivasertib, which studies suggest can significantly extend the time patients live without cancer worsening compared to standard treatments. Another arm will evaluate elacestrant with everolimus, which has kept the cancer from progressing for an average of 8.3 months. The combination of elacestrant with alpelisib, tested in a separate arm, showed positive results, extending the time without cancer progression to about 11 months. Additionally, other arms will explore combinations of elacestrant with ribociclib and palbociclib, which have shown promising outcomes in managing advanced breast cancer. These combinations highlight the potential of elacestrant as a helpful treatment option. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults with ER+/HER2- advanced/metastatic breast cancer who've had up to two hormonal therapies, one with a CDK4/6 inhibitor. They must have good organ function and performance status, no severe allergies to the drugs being tested, and agree to contraception if of childbearing potential. Those with certain prior treatments or health conditions are excluded.

Inclusion Criteria

My cancer has a PIK3CA mutation.

Patient has signed the informed consent before all study specific activities are conducted.

I am fully active or can carry out light work.

Exclusion Criteria

I do not have any severe ongoing infections.

QTcF values ≥450 msec.

I have been treated with everolimus before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1b Treatment

Determine the RP2D of elacestrant in combination with other drugs, with 1-3 cohorts of 6 DLT-evaluable patients each

28 days

Multiple visits for dose-limiting toxicity evaluation

Phase 2 Treatment

Evaluate the efficacy and safety of elacestrant in combination with other drugs in patients with ER+/HER2- advanced/metastatic breast cancer

6 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

What Are the Treatments Tested in This Trial?

Interventions

• Alpelisib
• Elacestrant
• Everolimus
• Palbociclib
• Ribociclib

Trial Overview The study tests Elacestrant in combination with other cancer drugs (Alpelisib, Everolimus, Ribociclib, Palbociclib) to find the best dose and assess safety/effectiveness against metastatic breast cancer. It's an open-label trial where everyone knows what treatment they're getting.

How Is the Trial Designed?

Group I: Phase 1b Arm E: Experimental Treatment 2 Interventions

Elacestrant Dihydrochloride 300 mg, 400 mg + Capivasertib 200 mg, 320 mg, 400 mg

Group II: Phase 1b Arm D: elacestrant with either palbociclib, abemaciclib, or ribociclib (no prior CDK4/6i) Experimental Treatment 4 Interventions

Elacestrant Dihydrochloride 300 mg or 400 mg + Palbociclib 100 mg,125 mg or the RP2D for the combination of elacestrant and abemaciclib is evaluated in the ongoing ELECTRA trial (ClinicalTrials.gov Identifier: NCT04791384) Elacestrant 86 mg, 172 mg, 258 mg + Ribociclib 400 mg or possibly 600 mg

Group III: Phase 1b Arm C: elacestrant with abemaciclib or ribociclib: Experimental Treatment 3 Interventions

Elacestrant Dihydrochloride 100 mg, 200 mg, 300 mg + Ribociclib 400 mg or possibly 600 mg The RP2D for the combination of elacestrant and abemaciclib is evaluated in the ongoing ELECTRA trial (ClinicalTrials.gov Identifier: NCT04791384)

Group IV: Phase 1b Arm B: elacestrant with everolimus Experimental Treatment 2 Interventions

Elacestrant Dihydrochloride 300 mg or 400 mg + Everolimus 5.0 mg, 7.5 mg or possibly 10 mg

Group V: Phase 1b Arm A: elacestrant with alpelisib Experimental Treatment 2 Interventions

Elacestrant Dihydrochloride 300 milligrams (mg) or 400 mg + Alpelisib 150 mg to 250 mg

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 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 (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 (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 (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]

In the phase III EMERALD trial, elacestrant, an oral selective estrogen receptor degrader, showed a statistically significant improvement in progression-free survival for patients with ER-positive/HER2-negative breast cancer.

This benefit was observed in patients who had already been treated with endocrine therapy and a CDK4/6 inhibitor, indicating elacestrant's potential as a valuable treatment option in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel SERD Has PFS Edge against Breast Cancer. [2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11558728/

Elacestrant plus alpelisib in an ESR1 and PIK3CA co ... An all-oral combination of elacestrant plus alpelisib was feasible, tolerable, and clinically active in an ESR1 and PIK3CA co-mutated and heavily pretreated ...

2. everyone.org everyone.org/explore/compare?id1=308&id2=550

Piqray (alpelisib) vs Orserdu (elacestrant) Patients treated with the combination had a median PFS of 11.0 months versus 5.7 months for those receiving fulvestrant plus placebo, indicating a substantial ...

3. onclive.com onclive.com/view/elacestrant-displays-potential-as-combination-backbone-in-er-breast-cancer-after-cdk4-6-inhibition

Elacestrant Displays Potential as Combination Backbone ... Elacestrant-based combinations were safe and displayed preliminary efficacy in ER-positive/HER2-negative advanced breast cancer.

4. piqray-hcp.com piqray-hcp.com/metastatic-breast-cancer/efficacy/efficacy-results

Efficacy Results | PIQRAY® (alpelisib) tablets View the results of the SOLAR-1 clinical trial for PIQRAY, including progression-free survival and overall response. See full Prescribing & Safety Info.

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

Elacestrant in ESR1-mutant, endocrine-responsive ... Accordingly, the landmark analysis showed 6- and 12-month PFS rates were doubled in the elacestrant arm (6 months: 41% versus 19%; 12 months: 27 ...

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

Post-marketing safety of elacestrant in breast cancer These data indicate that the safety profile of elacestrant in clinical trials is similar to that of other endocrine therapy drugs but with a ...

7. orserduhcp.com orserduhcp.com/safety/

Safety Profile & Adverse Reactions | ORSERDU® (elacestrant) View the safety profile and potential adverse reactions ER+/HER2-mBC patients experienced during the EMERALD study of ORSERDU®.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/217639s000lbl.pdf

ORSERDU (elacestrant) - accessdata.fda.gov The safety of ORSERDU was evaluated in 467 patients with ER+/HER2- advanced breast cancer following CDK4/6 inhibitor therapy in EMERALD, a randomized, open- ...

9. 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.

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12215442/

Evaluation of Safety of Elacestrant in Patients with Breast ... This study aims to evaluate the safety profile of elacestrant in real-world settings using data from the FDA adverse event (AE) reporting system (FAERS) ...