What is the mechanism of action of this treatment?

Breast cancer treatments often target specific pathways to inhibit cancer growth. Estrogen receptor degraders (ERDs) like ARV-471 work by binding to estrogen receptors on cancer cells, leading to their degradation and preventing estrogen from promoting cancer cell growth. mTOR inhibitors like everolimus block the mTOR pathway, which is crucial for cell growth and proliferation. By inhibiting this pathway, everolimus can reduce cancer cell growth and survival. These mechanisms are vital for breast cancer patients as they offer targeted approaches to slow down or stop the progression of hormone receptor-positive breast cancer, potentially improving outcomes and reducing the risk of resistance to other therapies.

What side effects are associated with this type of intervention?

Common treatments for breast cancer, such as estrogen receptor degraders and mTOR inhibitors, have several known side effects. Estrogen receptor degraders like tamoxifen can cause fatigue, hot flashes, and an increased risk of blood clots. mTOR inhibitors like everolimus are associated with side effects including fatigue, stomatitis (mouth sores), rash, anorexia, diarrhea, and hypercholesterolemia. These treatments can also lead to more serious adverse events such as hepatic cyst infections and increased risk of infections due to immunosuppression.

What prior FDA approvals exist?

The FDA has approved several treatments for breast cancer that target hormone receptors and mTOR pathways. Everolimus, an mTOR inhibitor, is approved for use in combination with exemestane for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer after failure of treatment with letrozole or anastrozole. Additionally, estrogen receptor degraders like fulvestrant have been approved for hormone receptor-positive metastatic breast cancer. These treatments aim to inhibit cancer cell growth by targeting specific pathways involved in cell proliferation and survival.

What other types of research exist?

Promising novel alternatives for breast cancer treatment in 2024 include: 1) CDK 4/6 inhibitors such as abemaciclib, which have shown efficacy in combination with endocrine and anti-HER2 therapy. 2) PARP inhibitors for patients with BRCA mutations, which target DNA repair mechanisms. 3) Immune checkpoint inhibitors like pembrolizumab for tumors with high microsatellite instability or mismatch repair deficiency. 4) Antibody-drug conjugates and other targeted therapies that are currently under investigation.

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Hormone Therapy

ARV-471 + Everolimus for Advanced Breast Cancer (TACTIVE-E Trial)

Phase 1

Waitlist Available

Research Sponsored by Arvinas Estrogen Receptor, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Women must be postmenopausal, or pre-/peri-menopausal women must be on ovarian suppression

Histologically or cytologically confirmed ER+ and HER2-advanced breast cancer (metastatic, recurrent, or unresectable)

Must not have

Any of the following in the previous 6 months: congenital long QT syndrome, Torsade de Pointes, sustained ventricular tachyarrhythmia and ventricular fibrillation, left anterior hemiblock, ongoing cardiac arrythmias/dysrhythmias, atrial fibrillation

Prior treatment targeting mTOR (e.g. everolimus)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new drug combination (ARV-471 and everolimus) for patients with advanced or metastatic ER+/HER2- breast cancer who have already tried other treatments. The drugs work together to slow down cancer growth by targeting estrogen receptors and blocking a growth pathway. Everolimus is used in combination with other treatments for advanced hormone-receptor-positive, HER2-negative breast cancer.

Who is the study for?

This trial is for postmenopausal women or those on ovarian suppression with advanced ER+/HER2- breast cancer. Participants must have tried and not responded well to certain therapies, including a CDK 4/6 inhibitor and endocrine therapy, but not treatments targeting mTOR like everolimus. They should be in good physical condition (ECOG status of 0 or 1) and agree to use a special mouthwash to prevent sores from the medication.

What is being tested?

The study tests ARV-471 combined with Everolimus in patients who've had up to three lines of previous cancer treatment. It's an early-phase trial aiming to see how safe this combination is and how it affects their type of breast cancer that has spread or cannot be surgically removed.

What are the potential side effects?

Possible side effects include mouth sores which are attempted to be prevented by dexamethasone mouthwash, increased risk of infections due to immune system impact, potential lung issues such as pneumonitis, blood pressure changes requiring medication control, and possibly other heart-related complications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am a woman who is either postmenopausal or taking medication to suppress my ovaries.

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My breast cancer is ER+ and HER2-, and cannot be removed by surgery.

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I am fully active or can carry out light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have not had serious heart rhythm problems in the last 6 months.

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I have been treated with drugs targeting mTOR.

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I haven't taken any cancer drugs or been in a study within the last 4 weeks.

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I have had lung problems caused by medication before.

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I haven't had radiation therapy in the last 4 weeks or to more than 25% of my bone marrow.

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I have previously been treated with ARV-471.

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I do not have any active, uncontrolled infections including HIV/AIDS or hepatitis.

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My high blood pressure is not controlled by medication.

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I have not had major surgery within the last 4 weeks.

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I have brain metastases not treated or need high doses of steroids.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Everolimus

Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-471 in combination with everolimus

Number of participants with adverse events as a measure of safety and tolerability of ARV-471 in combination with everolimus

Secondary study objectives

Clinical benefit rate (CBR) in participants.

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: ARV-471 and EverolimusExperimental Treatment1 Intervention

ARV-471 oral tablets in combination with everolimus administered daily in 28 day cycles

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Breast cancer treatments often target specific pathways to inhibit cancer growth. Estrogen receptor degraders (ERDs) like ARV-471 work by binding to estrogen receptors on cancer cells, leading to their degradation and preventing estrogen from promoting cancer cell growth. mTOR inhibitors like everolimus block the mTOR pathway, which is crucial for cell growth and proliferation. By inhibiting this pathway, everolimus can reduce cancer cell growth and survival. These mechanisms are vital for breast cancer patients as they offer targeted approaches to slow down or stop the progression of hormone receptor-positive breast cancer, potentially improving outcomes and reducing the risk of resistance to other therapies.