What is the mechanism of action of this treatment?

Antibody-drug conjugates (ADCs) like Trastuzumab Deruxtecan target the HER2 receptor on breast cancer cells, combining the specificity of monoclonal antibodies with the cytotoxic potency of chemotherapy. These drugs bind to HER2, delivering a cytotoxic agent directly to the tumor, which enhances treatment efficacy and minimizes damage to healthy cells. This targeted approach is crucial for breast cancer patients as it improves outcomes and reduces systemic side effects. Other treatments, such as trastuzumab and pertuzumab, also target HER2, blocking its signaling pathways and inhibiting tumor growth. Understanding these mechanisms allows for personalized treatment plans, optimizing efficacy and side effect management.

What side effects are associated with this type of intervention?

Common treatments for HER2-positive breast cancer, such as Trastuzumab Deruxtecan and Trastuzumab Emtansine, are associated with several side effects. The most frequently reported side effects include decreased neutrophil count, anemia, nausea, fatigue, and diarrhea. Severe side effects can include interstitial lung disease, which has been fatal in some cases, and cardiotoxicity, such as a drop in left ventricular ejection fraction. Patients undergoing these treatments should be closely monitored for respiratory symptoms and cardiac function.

What prior FDA approvals exist?

The FDA has approved several treatments for HER2-positive breast cancer, including antibody-drug conjugates like Trastuzumab Deruxtecan (T-DXd) and Ado-trastuzumab emtansine (T-DM1). Trastuzumab Deruxtecan is approved for patients with HER2-positive metastatic breast cancer who have received prior anti-HER2-based regimens. Ado-trastuzumab emtansine is another approved option for patients who have progressed after treatment with trastuzumab and a taxane. These treatments are part of a broader category of HER2-targeted therapies that have shown efficacy in managing advanced breast cancer.

What other types of research exist?

Promising alternatives to Trastuzumab Deruxtecan for HER2-positive breast cancer include: <ol> <li>Tucatinib-Trastuzumab-Capecitabine regimen, which has shown efficacy in treating leptomeningeal metastasis in HER2-positive breast cancer.</li> <li></li> </ol> Trastuzumab Emtansine (T-DM1), which has demonstrated effectiveness in patients with brain metastases and is a well-established treatment option. 3. Lapatinib plus Capecitabine, which has been used in various combinations and has shown positive outcomes in metastatic settings. 4. Abemaciclib plus Trastuzumab with or without Fulvestrant, which has shown promise in hormone receptor-positive, HER2-positive advanced breast cancer.

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Monoclonal Antibodies

Trastuzumab Deruxtecan for Metastatic Breast Cancer

Phase 3

Waitlist Available

Research Sponsored by Daiichi Sankyo

Eligibility Criteria Checklist

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

Must have

Has low-HER2 expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested)

Has adequate archival tumor samples available or is willing to provide fresh biopsies prior to randomization for assessment of HER2 status and post-treatment status

Must not have

Has previously been treated with any anti-HER2 therapy, including an antibody drug conjugate

Has spinal cord compression or clinically active central nervous system metastases

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from screening and every 6 weeks up to withdrawal of subject consent, progressive disease (pd), or unacceptable toxicity, up to approximately 3 years

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial will compare trastuzumab deruxtecan to other treatments for patients with HER2-low breast cancer that cannot be removed by surgery and has spread. The treatment targets and kills cancer cells by delivering chemotherapy directly to them. Trastuzumab deruxtecan has shown effectiveness in patients with HER2-low breast cancer, resulting in longer periods without the disease getting worse and longer life expectancy compared to other chemotherapy treatments.

Who is the study for?

This trial is for adults with HER2-low breast cancer that's inoperable or has spread, and who have tried endocrine therapy without success. They should have had 1-2 prior chemotherapy treatments in the metastatic setting, be able to provide tumor samples, and not have high-HER2 cancer or a history of certain lung conditions.

What is being tested?

The study compares DS-8201a (Trastuzumab Deruxtecan) with standard treatments chosen by physicians such as Eribulin, Paclitaxel, Gemcitabine, Capecitabine or Nab-paclitaxel. Participants will receive either the new drug or one of these existing drugs based on their doctor's choice.

What are the potential side effects?

Possible side effects include allergic reactions to medication components, fatigue, nausea and vomiting from chemotherapy drugs. Trastuzumab Deruxtecan may cause issues like hair loss and low blood cell counts leading to increased infection risk.

Eligibility Criteria

Inclusion Criteria

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

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My cancer has low levels of HER2.

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I can provide samples of my tumor for testing before treatment starts.

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My cancer has grown or spread on my latest scans.

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My breast cancer cannot be surgically removed or has spread.

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I am legally considered an adult in my country.

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My condition worsened despite hormone therapy.

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My heart, liver, kidneys, bone marrow, and blood clotting functions are all within normal ranges.

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My cancer was never previously tested positive for HER2.

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I've had 1-2 rounds of chemotherapy for my cancer after it came back or spread.

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My cancer is either hormone receptor positive or negative.

Exclusion Criteria

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

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I have been treated with a HER2-targeting therapy before.

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I have spinal cord compression or active brain metastases.

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My breast cancer has high levels of HER2.

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I have serious heart problems that are not under control.

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I cannot receive any standard treatments my doctor would normally choose.

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I have or had lung inflammation that needed steroids, or it's suspected but not confirmed by scans.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from screening and every 6 weeks up to withdrawal of subject consent, progressive disease (pd), or unacceptable toxicity, up to approximately 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from screening and every 6 weeks up to withdrawal of subject consent, progressive disease (pd), or unacceptable toxicity, up to approximately 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and from screening and every 6 weeks up to withdrawal of subject consent, progressive disease (pd), or unacceptable toxicity, up to approximately 3 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer

Secondary study objectives

Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients)

Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer

Duration of Response in Participants With HER2-low Breast Cancer (All Patients)

+6 more

Other study objectives

All-Cause Mortality

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Trastuzumab deruxtecanExperimental Treatment1 Intervention

HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to DS8201a

Group II: Physician's ChoiceActive Control5 Interventions

HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to Physician's choice from the following options: * Capecitabine * Eribulin * Gemcitabine * Paclitaxel * Nab-paclitaxel

0 / 16Eligibility 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

Antibody-drug conjugates (ADCs) like Trastuzumab Deruxtecan target the HER2 receptor on breast cancer cells, combining the specificity of monoclonal antibodies with the cytotoxic potency of chemotherapy. These drugs bind to HER2, delivering a cytotoxic agent directly to the tumor, which enhances treatment efficacy and minimizes damage to healthy cells. This targeted approach is crucial for breast cancer patients as it improves outcomes and reduces systemic side effects. Other treatments, such as trastuzumab and pertuzumab, also target HER2, blocking its signaling pathways and inhibiting tumor growth. Understanding these mechanisms allows for personalized treatment plans, optimizing efficacy and side effect management.

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