What side effects are associated with this type of intervention?

The most common treatments for HER2-positive breast cancer, such as Trastuzumab Deruxtecan (DS-8201a) and Ado-Trastuzumab Emtansine (T-DM1), are associated with several side effects. Trastuzumab Deruxtecan can cause decreased neutrophil count, anemia, nausea, and interstitial lung disease, which requires monitoring for respiratory symptoms. Ado-Trastuzumab Emtansine is associated with fatigue, nausea, increased liver function tests, and in rare cases, serious cardiac and pulmonary events. Both treatments are generally well-tolerated but require careful monitoring for these potential adverse effects.

What prior FDA approvals exist?

The FDA has approved several treatments for HER2-positive breast cancer, including antibody-drug conjugates like Trastuzumab Deruxtecan (DS-8201a) and Ado-Trastuzumab Emtansine (T-DM1). Trastuzumab Deruxtecan has shown significant efficacy in patients with metastatic breast cancer who have progressed on prior HER2-directed therapies, with a notable intracranial response rate in those with brain metastases. T-DM1 is approved for patients who have progressed after treatment with trastuzumab and a taxane, demonstrating improved progression-free and overall survival compared to other therapies. Other related treatments include combinations like tucatinib, capecitabine, and trastuzumab, which have also shown improved outcomes in patients with brain metastases.

What other types of research exist?

Promising novel alternatives to DS-8201a and T-DM1 for HER2-positive breast cancer include the combination of tucatinib, capecitabine, and trastuzumab, which has shown improved PFS and OS in the HER2CLIMB trial. Another alternative is the combination of neratinib and capecitabine, which has supporting data from phase II studies. These alternatives offer additional options for patients who have progressed on prior HER2-directed therapies.

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Monoclonal Antibody

T-DXd vs T-DM1 for HER2-Positive 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 confirmed HER2-positive expression as determined according to American Society of Clinical Oncology - College of American Pathologists guidelines evaluated at a central laboratory

Has pathologically documented breast cancer that is unresectable or metastatic

Must not have

Has a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening

Has spinal cord compression or clinically active central nervous system (CNS) metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 33 months (data cut-off)

Awards & highlights

No Placebo-Only Group

Pivotal Trial

All Individual Drugs Already Approved

Summary

This trial compares two drugs, DS-8201a and T-DM1, for treating a specific type of breast cancer that hasn't responded to other treatments. These drugs work by targeting a protein on cancer cells to deliver a toxic substance that kills the cancer. T-DM1 has shown significant improvements in patients with HER2-positive breast cancer who have not responded to previous treatments.

Who is the study for?

This trial is for adults with HER2-positive, unresectable or metastatic breast cancer who have previously been treated with trastuzumab and taxane. They must have adequate organ function and agree to use effective contraception. Those with symptomatic brain metastases, a history of certain lung conditions, uncontrolled heart disease, or previous anti-HER2 ADC treatment in the metastatic setting are excluded.

What is being tested?

The study compares DS-8201a (Trastuzumab deruxtecan) against T-DM1 (Ado-trastuzumab emtansine) in terms of tumor control and overall safety for patients with advanced HER2-positive breast cancer that has not responded to initial treatments.

What are the potential side effects?

Potential side effects include reactions related to infusion, lung issues like interstitial lung disease/pneumonitis, liver toxicity which may affect organ function tests, fatigue, nausea and potential harm to an unborn child hence the need for effective contraception.

Eligibility Criteria

Inclusion Criteria

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

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My cancer is confirmed HER2-positive by specific guidelines.

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My breast cancer cannot be surgically removed or has spread.

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My most recent tumor sample is HER2 positive, or I agree to a new biopsy if needed.

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I was treated with trastuzumab and taxane for advanced cancer or it worsened within 6 months after similar treatment.

Exclusion Criteria

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

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I have or had lung inflammation that needed steroids, or it might be seen in my recent lung scans.

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I have untreated, symptomatic brain or spinal cord metastases requiring medication.

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I have serious heart problems that are not under control.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 33 months (data cut-off)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 33 months (data cut-off)

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 33 months (data cut-off) 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 Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane

Secondary study objectives

Duration of Response (DoR) Based on BICR and Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane

Overall Survival (OS) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane

Percentage of Participants With Objective Response Rate (ORR) Based on BICR and Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane

+1 more

Awards & Highlights

No Placebo-Only Group

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

Pivotal Trial

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

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Trastuzumab deruxtecan (T-DXd)Experimental Treatment1 Intervention

Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).

Group II: Ado-trastuzumab emtansine (T-DM1)Active Control1 Intervention

Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DM1 in accordance with the approved label.

0 / 7Eligibility 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 (DS-8201a) and Ado-Trastuzumab Emtansine (T-DM1) are targeted cancer therapies that combine the specificity of monoclonal antibodies with the potency of cytotoxic drugs. These ADCs target the HER2 receptor, which is overexpressed in some breast cancers. Trastuzumab Deruxtecan delivers a topoisomerase inhibitor directly to cancer cells, causing DNA damage and cell death. Ado-Trastuzumab Emtansine delivers a microtubule inhibitor, disrupting cell division. These targeted approaches minimize damage to healthy cells and improve treatment efficacy, offering significant benefits for patients with HER2-positive breast cancer by potentially improving survival rates and reducing side effects.

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