What side effects are associated with this type of intervention?

Common treatments for HER2-positive breast cancer, such as Trastuzumab deruxtecan (T-DXd), Trastuzumab emtansine (T-DM1), trastuzumab, pertuzumab, and lapatinib, have several known side effects. T-DXd can cause decreased neutrophil count, anemia, nausea, and interstitial lung disease, which requires monitoring for respiratory symptoms. T-DM1 shares similar side effects, including thrombocytopenia and elevated liver enzymes. Trastuzumab and pertuzumab are generally well-tolerated but can lead to cardiac dysfunction, necessitating regular heart function monitoring. Lapatinib may cause diarrhea, rash, and hepatotoxicity. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several antibody-drug conjugates (ADCs) targeting HER2 for the treatment of breast cancer. Trastuzumab emtansine (T-DM1) is one such ADC, approved for patients who have progressed after treatment with trastuzumab and a taxane. T-DM1 has shown efficacy in patients with treated, stable brain metastases, with CNS objective response rates (ORRs) between 20 and 44 percent. Another ADC, Trastuzumab deruxtecan (T-DXd), has been approved for patients with HER2-positive metastatic breast cancer who have progressed on prior anti-HER2-based regimens. T-DXd has demonstrated a median progression-free survival (PFS) of 16 months in heavily pretreated patients, though it is associated with risks such as interstitial lung disease.

What other types of research exist?

Promising alternatives to Trastuzumab deruxtecan for HER2-positive breast cancer patients include: 1) Tucatinib in combination with Trastuzumab and Capecitabine, which has shown efficacy in treating brain metastases. 2) Trastuzumab emtansine (T-DM1), another antibody-drug conjugate targeting HER2, which has demonstrated effectiveness in various studies. 3) Dual HER2 blockade with Lapatinib plus Trastuzumab, particularly in combination with an aromatase inhibitor for hormone receptor-positive cases. These alternatives offer different mechanisms of action and potential benefits for patients with advanced or metastatic HER2-positive breast cancer.

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Antibody-Drug Conjugate

T-DXd for HER2 Positive Breast Cancer (DESTINY-B12 Trial)

Phase 3

Waitlist Available

Led By Nadia Harbeck, MD, PhD

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

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

Must have

Eastern Cooperative Oncology Group performance status 0-1

Participants with BMs must be neurologically stable

Must not have

Participants with a medical history of myocardial infarction within 6 months before screening, symptomatic congestive heart failure (New York Heart Association Class II to IV)

Known or suspected leptomeningeal disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from screening until pd (up to 2.5 years)

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a new cancer drug called Trastuzumab deruxtecan in patients with advanced HER2-positive breast cancer that has not responded to other treatments. The drug targets cancer cells with a specific marker and delivers a powerful drug to kill them. The study includes patients with and without brain metastasis to see how well the drug works and how safe it is. Trastuzumab deruxtecan is a new type of treatment that has shown impressive results in patients who have already received many other treatments.

Who is the study for?

This trial is for people with advanced or metastatic HER2 positive breast cancer who have had disease progression after prior anti-HER2 therapies and no more than two treatments in the metastatic setting. It includes those with or without brain metastasis (BMs), provided BMs are stable, untreated but not needing immediate therapy, or previously treated. Participants must be physically capable (ECOG 0-1), have a heart ejection fraction ≥50%, and women of childbearing potential must test negative for pregnancy.

What is being tested?

The study tests Trastuzumab Deruxtecan (T-DXd) on participants to evaluate its effectiveness and safety. The trial is open-label, meaning everyone knows which treatment they're getting, and it's conducted at multiple centers internationally. Patients included may have measurable lesions suitable for repeated assessments or non-measurable bone-only diseases assessable by scans.

What are the potential side effects?

While specific side effects of T-DXd aren't listed here, common ones from similar treatments include fatigue, nausea, hair loss (alopecia), blood cell count changes increasing infection risk, heart problems like reduced ejection fraction leading to heart failure symptoms, potential liver issues indicated by hepatitis exclusion criteria, possible lung inflammation/pneumonitis requiring steroids treatment.

Eligibility Criteria

Inclusion Criteria

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

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You are in good enough health to carry out daily activities without limitations (Eastern Cooperative Oncology Group performance status 0-1).

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If you have brain metastases, you must be neurologically stable.

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You have been diagnosed with advanced or metastatic breast cancer and have been confirmed to have HER2-positive cancer.

Exclusion Criteria

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

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You had a heart attack or have significant heart failure symptoms within the past 6 months.

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You have a known or suspected disease affecting the covering of the brain and spinal cord.

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You have already taken tucatinib before.

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You have ongoing severe nausea and vomiting, long-term stomach or bowel problems, or a history of major bowel surgery that might affect how your body processes T-DXd.

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You have spinal cord compression.

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You have an infection that is not being controlled by regular antibiotics, antiviral or antifungal medications.

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You have had radiation treatment to a certain area of your body within a specific time frame before starting the study.

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You got a live vaccine within 30 days before starting the T-DXd treatment.

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You still have side effects from your previous cancer treatment that have not gotten better.

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You have serious ongoing health issues related to your lungs, or autoimmune, connective tissue, or inflammatory disorders.

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You have had lung problems in the past that needed steroids, currently have lung problems, or might have lung problems that can't be ruled out by imaging tests.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from screening until pd (up to 2.5 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from screening until pd (up to 2.5 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from screening until pd (up to 2.5 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

Objective Response Rate (ORR) in Participants without BM at Baseline (Cohort 1)

Progression-free Survival (PFS) in Participants with BM at Baseline (Cohort 2)

Secondary study objectives

Central Nervous System Duration of Response in Participants with BM at Baseline (Cohort 2)

Defecation

Central Nervous System Progression-free Survival in Participants with BM at Baseline (Cohort 2)

+18 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.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Trastuzumab DeruxtecanExperimental Treatment1 Intervention

Participants with or without BM at baseline will receive intravenous (IV) T-DXd, 5.4 mg/kg, every 3 weeks (21-day cycle) until Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) defined radiological progression outside central nervous system, unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Trastuzumab Deruxtecan

2021

Completed Phase 2

~100

0 / 15Eligibility 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

HER2-targeted therapies, such as Trastuzumab deruxtecan, work by binding to the HER2 protein on the surface of cancer cells, inhibiting their growth and survival. Trastuzumab deruxtecan is an antibody-drug conjugate that combines the specificity of trastuzumab (an anti-HER2 antibody) with a cytotoxic drug, delivering targeted chemotherapy directly to cancer cells. This dual mechanism enhances efficacy while minimizing systemic toxicity. These treatments are vital for managing HER2-positive breast cancer, offering improved outcomes and tailored therapeutic options for patients.

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