Elacestrant + Trastuzumab Deruxtecan for Breast Cancer

(ERADICATE Trial)

Not yet recruiting at 1 trial location

Overseen By Sarah Sammons, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sarah Sammons, MD

Must be taking: GnRH agonist

Must not be taking: Antibody-drug conjugates, SERD

Disqualifiers: Symptomatic brain metastases, Active tuberculosis, others

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

Compensation: Varies

Number of Visits: 16

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, elacestrant (a type of hormone therapy) and trastuzumab deruxtecan (an antibody-drug conjugate), to determine their safety and effectiveness in treating a specific type of breast cancer. It targets hormone receptor-positive, HER2-low metastatic breast cancer that hasn't responded to certain previous treatments. Individuals with this cancer type, who have experienced progression despite past use of CDK4/6 inhibitors and endocrine therapy, might be suitable candidates. Participants will receive the study drugs and undergo regular imaging and biopsies to monitor their response. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial requires a 7-day period without taking any endocrine or targeted therapy before starting the study treatment. If you're on such medications, you will need to stop them for at least a week before joining the trial.

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

Earlier studies have shown that elacestrant and trastuzumab deruxtecan are generally safe. Data from the ELEVATE study indicated that using these drugs together was mostly well-tolerated by patients with advanced breast cancer, with most side effects being mild and manageable.

Trastuzumab deruxtecan has been widely used in other cancer treatments and found effective, with manageable side effects like nausea and tiredness. Similarly, elacestrant has been tested in various contexts, focusing on safety, and patients have generally tolerated it well.

As this trial is in its early stages, the main goal is to ensure safety and determine the best dose. Researchers are closely monitoring for any side effects to protect participants. Always consult your healthcare provider to determine if this trial is suitable for you. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Elacestrant paired with Trastuzumab Deruxtecan because they bring a new approach to treating breast cancer. While standard treatments often focus on hormone blockers or chemotherapy, Elacestrant is a selective estrogen receptor degrader (SERD) that targets estrogen receptors directly, potentially offering a more precise attack on cancer cells. Trastuzumab Deruxtecan, on the other hand, is an antibody-drug conjugate, which combines targeted therapy with chemotherapy, delivering the drug directly to cancer cells with less impact on healthy cells. This combination has the potential to enhance effectiveness while reducing side effects, offering a promising new option for patients.

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

Studies have shown that elacestrant is effective for patients with HR-positive, HER2-negative advanced breast cancer, particularly those with an ESR1 mutation. In these patients, the cancer worsened after an average of 8.6 months. Trastuzumab deruxtecan has also delivered promising results, with over a third of patients experiencing tumor shrinkage. Additionally, about 75% of patients achieved some form of disease control, helping to manage cancer progression. This trial will explore the combination of elacestrant and trastuzumab deruxtecan, which could potentially enhance their effectiveness, as both have demonstrated benefits in treating advanced breast cancer. ^{1 5 6 7 8}

Who Is on the Research Team?

Sarah Sammons, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with HR+/HER2-low or HER2-ultralow metastatic breast cancer that hasn't responded to previous CDK4/6 inhibitor and endocrine therapies. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may be excluded based on factors like other medical conditions or treatments.

Inclusion Criteria

Participants must have measurable disease per RECIST 1.1 criteria

Participants must agree to use adequate contraception

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Receipt of any other investigational compound or device within 2 weeks of the first dose of treatment in this study

History of allergic reactions to compounds similar to elacestrant or T-DXd

Patients who are pregnant, breastfeeding, or planning pregnancy within specified timeframes

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase Ib Treatment

Dose-escalation to determine the recommended phase II dose of Elacestrant in combination with trastuzumab deruxtecan

21 days

Cycle 1: Days 1 through 21 with daily dosing

Phase II Treatment

Expansion to evaluate efficacy and safety at the recommended phase II dose

Up to 36 months

Imaging every 9 weeks until Cycle 9, then every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 6 months

Follow-up visits every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Elacestrant
• Trastuzumab Deruxtecan

Trial Overview The study tests the combination of Elacestrant (selective estrogen receptor degrader) and Trastuzumab Deruxtecan (antibody drug conjugate) in patients with a specific type of advanced breast cancer. It aims to assess the safety and effectiveness of this treatment regimen.

How Is the Trial Designed?

Group I: Phase 2: Elacestrant + Trastuzumab Deruxtecan Experimental Treatment 2 Interventions

37 participants will complete the following: * Baseline visit -Cycle 1 (21 day cycle) * Days 1 through 21: Predetermined dose of Elacestrant 1x daily. * Day 1: Predetermined dose of Trastuzumab Deruxtecan 1x daily. -Cycle 2 through End of Treatment (21 day cycle): * Imaging every 9 weeks until Cycle 9, then every 12 weeks * Day 1: tumor biopsy * Days 1 through 21: Predetermined dose of Elacestrant 1x daily. * Day 1: Predetermined dose of Trastuzumab Deruxtecan 1x daily. * End of Treatment visit with imaging * Follow up visits every 6 months

Group II: Phase 1b: Elacestrant + Trastuzumab Deruxtecan Experimental Treatment 2 Interventions

Up to 28 participants will be enrolled to determine the recommended phase 2 dosage of Elacestrant and will complete the following: * Baseline visit * Cycle 1 (21 day cycle) * Days 1 through 21: Predetermined dose of Elacestrant 1x daily. * Day 1: Predetermined dose of Trastuzumab Deruxtecan 1x daily. * Cycle 2 through End of Treatment (21 day cycle): * Imaging every 9 weeks until Cycle 9, then every 12 weeks * Day 1: tumor biopsy * Days 1 through 21: Predetermined dose of Elacestrant 1x daily. * Day 1: Predetermined dose of Trastuzumab Deruxtecan 1x daily. * End of Treatment visit with imaging * Follow up visits every 6 months * If 3 or less out of 12 participants experience a dose-limiting toxicity (DLT), the recommended Phase II dose of Elacestrant will be that dose level. If there are 4 or more DLTs, Elacestrant dosage will de-escalate and 12 more participants will be enrolled.

Who Is Running the Clinical Trial?

Sarah Sammons, MD

Lead Sponsor

Trials

3

Recruited

110+

Stemline Therapeutics, Inc.

Industry Sponsor

Trials

24

Recruited

6,500+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07198724

ERADICATE: A Phase Ib/​II Study of Elacestrant Plus ... The goal of this study is to evaluate the safety and efficacy of elacestrant in combination with trastuzumab deruxtecan (T-DXd) in participants with hormone ...

2. onclive.com onclive.com/view/elacestrant-and-trastuzumab-deruxtecan-approvals-prompt-sequencing-considerations-in-hr-breast-cancer

Elacestrant and Trastuzumab Deruxtecan Approvals ... One was the recent approval of elacestrant for patients with HR-positive, HER2-negative advanced breast cancer who harbor an ESR1 mutation.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12594972/

Real-world outcomes of trastuzumab deruxtecan in HR ... The median lines of therapy were 3 (range 1–7). The objective response rate (ORR) was 35.9%, and the disease control rate was 75%. Median real- ...

4. esmoopen.com esmoopen.com/article/S2059-7029(25)00838-5/pdf

A meta-analysis Conclusions: Trastuzumab deruxtecan represents a promising advancement in breast cancer treatment, demonstrating enhanced efficacy. However, its safety profile ...

5. ascopost.com ascopost.com/issues/july-25-2023/two-studies-highlight-benefits-in-quality-of-life-and-symptom-management-with-novel-treatments-of-advanced-breast-cancer/

Two Studies Highlight Benefits in Quality of Life and ... In patients who had received prior treatment with CDK4/6 inhibitors and had ESR1 mutations, the median progression-free survival was 8.6 months ...

6. onclive.com onclive.com/view/elacestrant-combinations-in-er-her2--locally-advanced-or-metastatic-breast-cancer-efficacy-and-safety-updates-from-the-phase-1b-2-elevate-study

Elacestrant Combinations in ER+/HER2- Locally Advanced ... Presented by Dr. Hope S. Rugo, this slide deck presents updated phase 1b/2 safety and efficacy results from the ELEVATE trial of elacestrant ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11893322/

Safety and efficacy of combined trastuzumab-deruxtecan and ... This retrospective multicenter study included 54 patients treated concurrently with T-DXd and RT for HER2+ and HER2 low MBC between February ...

8. dailyreporter.esmo.org dailyreporter.esmo.org/esmo-breast-cancer-2023/esmo-breast-congress-2023/extended-safety-information-and-pros-data-support-key-trial-results-in-metastatic-breast-cancer

PROs data from key trial results in metastatic breast cancer, Data presentations from DESTINY-Breast04, DESTINY-Breast02 and EMERALD trials confirm the value of trastuzumab deruxtecan and elacestrant.