What is the mechanism of action of this treatment?

HER2-targeted therapies, such as Trastuzumab deruxtecan, are crucial for treating HER2-positive breast cancer. These treatments work by combining a HER2-targeting antibody with a cytotoxic drug, which is delivered directly to cancer cells, thereby inhibiting their growth and minimizing damage to normal cells. Other similar treatments include Trastuzumab, which blocks HER2 signaling, and Ado-trastuzumab emtansine, another antibody-drug conjugate. These therapies improve treatment efficacy and reduce side effects, offering significant benefits over traditional chemotherapy.

What side effects are associated with this type of intervention?

Common treatments for breast cancer, particularly those targeting HER2 like Trastuzumab deruxtecan (T-DXd) and Trastuzumab emtansine (T-DM1), have several known side effects. T-DXd is associated with decreased neutrophil count, anemia, nausea, and interstitial lung disease, which can be severe and potentially fatal. T-DM1 also causes similar side effects, including fatigue, nausea, and liver function abnormalities. Both treatments require careful monitoring for respiratory symptoms and other adverse effects. Other HER2-targeted therapies, such as trastuzumab, can lead to cardiac events, especially in older patients. Endocrine therapies like tamoxifen and aromatase inhibitors may cause bone density loss, fractures, and cardiovascular risks.

What prior FDA approvals exist?

The FDA has approved several treatments for HER2-positive breast cancer, including antibody-drug conjugates like trastuzumab emtansine (T-DM1) and fam-trastuzumab deruxtecan (T-DXd). Trastuzumab emtansine (T-DM1) is approved for patients who have progressed after trastuzumab and a taxane, showing CNS objective response rates (ORRs) between 20 and 44 percent. Fam-trastuzumab deruxtecan (T-DXd) has shown a median progression-free survival (PFS) of 16 months in heavily pretreated patients. Other related drugs include neratinib combined with capecitabine, approved for patients who have received two or more prior anti-HER2 regimens, and lapatinib plus capecitabine, an option for those progressing on trastuzumab.

What other types of research exist?

Promising alternatives to Trastuzumab deruxtecan for breast cancer patients include: 1) Trastuzumab emtansine (T-DM1), another antibody-drug conjugate targeting HER2, which has shown efficacy in HER2-positive breast cancer. 2) Dual HER2 blockade with Lapatinib plus Trastuzumab, which has demonstrated effectiveness in combination with aromatase inhibitors. 3) Abemaciclib plus Trastuzumab with or without Fulvestrant, which has shown promise in hormone receptor-positive, HER2-positive advanced breast cancer. These alternatives offer different mechanisms of action and may provide effective treatment options for patients.

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Monoclonal Antibodies

Trastuzumab Deruxtecan for Breast Cancer (DB-06 Trial)

Phase 3

Waitlist Available

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

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

Must have

No prior chemotherapy for advanced or metastatic breast cancer

Has protocol-defined adequate organ and bone marrow function

Must not have

Uncontrolled or significant cardiovascular disease or infection

Patients with spinal cord compression or clinically active central nervous system metastases

Timeline

Screening 3 weeks

Treatment Varies

Follow Up assessed up to approximately 60 months

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a new drug called trastuzumab deruxtecan for patients with advanced breast cancer that hasn't responded to other treatments. The drug works by specifically targeting and killing cancer cells. The study aims to see if this drug helps patients live longer or improves their quality of life compared to other treatments. Trastuzumab deruxtecan has shown significant clinical benefits in treating advanced breast cancer and other similar tumors.

Who is the study for?

This trial is for adults over 18 with advanced or metastatic breast cancer that has low HER2 expression and progressed after endocrine therapy. Participants must not have had prior chemotherapy for their advanced cancer, should have adequate organ function, and provide tumor samples to confirm HER2 status. Those with significant lung disease, uncontrolled heart conditions, active infections, or a history of certain lung problems are excluded.

What is being tested?

The study compares the effectiveness of Trastuzumab Deruxtecan (T-DXd) against standard chemotherapies like Capecitabine and Paclitaxel in patients with specific types of breast cancer. It aims to see which treatment is better at controlling the disease while monitoring safety and tolerability.

What are the potential side effects?

Trastuzumab Deruxtecan can cause side effects such as fatigue, nausea, hair loss, decreased blood cell counts increasing infection risk, potential heart damage or interstitial lung disease. Standard chemotherapies may also lead to similar side effects including nerve damage from Paclitaxel.

Eligibility Criteria

Inclusion Criteria

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

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I haven't had chemotherapy for advanced breast cancer.

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My organs and bone marrow are functioning well.

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My breast cancer is advanced or has spread, and tests show specific HER2 levels.

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I am 18 years old or older.

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My condition worsened after treatment within a specific timeframe.

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I have enough tumor samples for HER2 testing.

Exclusion Criteria

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

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I do not have serious heart disease or infections.

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I have spinal cord compression or active brain metastases.

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I cannot receive standard chemotherapy treatments.

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I have no serious lung illnesses besides my cancer.

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I have or had lung inflammation that needed steroids.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ assessed up to approximately 60 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~assessed up to approximately 60 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and assessed up to approximately 60 months 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) - in HR+, HER2-low populaton

Secondary study objectives

Duration of response (DoR) - in HR+, HER-2 low populaton

Duration of response (DoR) - in the ITT population

Health-related quality of life - EORTC QLQ-BR45

+12 more

Side effects data

From 2024 Phase 2 trial • 79 Patients • NCT04014075

65%

Nausea

44%

Vomiting

42%

Fatigue

38%

Anaemia

37%

Diarrhoea

35%

Weight Decreased

33%

Decreased Appetite

29%

Constipation

24%

Alopecia

18%

Platelet Count Decreased

16%

Hypokalaemia

16%

Neutrophil Count Decreased

16%

Aspartate Aminotransferase Increased

15%

Asthenia

14%

Abdominal Pain

11%

Cough

11%

Pyrexia

11%

White Blood Cell Count Decreased

11%

Blood Alkaline Phosphatase Increased

10%

Epistaxis

10%

Hypoalbuminaemia

10%

Neutropenia

10%

Gastrooesophageal Reflux Disease

10%

Alanine Aminotransferase Increased

Dyspnoea

Back Pain

Headache

Hypotension

Hyponatraemia

Dizziness

Pneumonitis

Ascites

Urinary Retention

Abdominal Pain Upper

Dysphagia

Covid-19

Insomnia

Thrombocytopenia

Weight Increased

Blood Bilirubin Increased

Interstitial Lung Disease

Acute Kidney Injury

Device Related Infection

Hypophosphataemia

Depression

Flatulence

Mucosal Inflammation

Blood Creatinine Increased

Urinary Tract Infection

Oedema Peripheral

Pneumonia

Disease Progression

Malignant Neoplasm Progression

Hyperpyrexia

Colitis

Haematemesis

Wound Infection

Bacterial Sepsis

Staphylococcal Infection

Covid-19 Pneumonia

Intestinal Obstruction

Animal Bite

Enteritis

Basal Ganglia Infarction

Cerebrovascular Accident

Generalised Tonic-Clonic Seizure

Pulmonary Embolism

Lymphangiosis Carcinomatosa

Tumour Haemorrhage

Bile Duct Stenosis

Hepatotoxicity

Hydronephrosis

Urinary Tract Obstruction

Exposure To Communicable Disease

Device Occlusion

Catheter Site Infection

100%

80%

60%

40%

20%

Study treatment Arm

Trastuzumab Deruxtecan

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

2Treatment groups

Experimental Treatment

Active Control

Group I: Trastuzumab deruxtecanExperimental Treatment1 Intervention

Trastuzumab deruxtecan (T-DXd; DS-8201a) arm

Group II: Standard of CareActive Control3 Interventions

Investigator's choice standard of care chemotherapy (capecitabine, paclitaxel, nab-paclitaxel) arm

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Trastuzumab deruxtecan

2021

Completed Phase 2

~730

0 / 11Eligibility 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, are crucial for treating HER2-positive breast cancer. These treatments work by combining a HER2-targeting antibody with a cytotoxic drug, which is delivered directly to cancer cells, thereby inhibiting their growth and minimizing damage to normal cells. Other similar treatments include Trastuzumab, which blocks HER2 signaling, and Ado-trastuzumab emtansine, another antibody-drug conjugate. These therapies improve treatment efficacy and reduce side effects, offering significant benefits over traditional chemotherapy.