Active not recruitingPHASE3INTERVENTIONAL

Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer

This study is testing a new treatment called trastuzumab deruxtecan. It's for people with advanced or metastatic breast cancer where the cancer has particular features: it's 'HER2-low' and 'hormone receptor positive'. This means your cancer cells have certain markers on them. We're comparing this new drug to regular chemotherapy, chosen by your doctor. The main goal is to find out if trastuzumab deruxtecan can help people live longer without their cancer growing, or simply live longer overall. We also want to understand how it affects people's quality of life. This trial is for people whose cancer has already progressed after previous hormone treatments.

At a glance

Status

Active not recruiting

Phase

PHASE3

Sponsor

AstraZeneca

Enrolment target

866

Start

24 Jul 2020

Estimated completion

19 Jun 2026

Advanced or Metastatic Breast Cancer

Results

Results from this study

Posted April 2025

Results have been published for this study.

Primary outcome

Progression-Free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2 (HER2)-Low Population

PFS per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) assessed by BICR was defined as the time from the date of randomization until the date of PD, as defined or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions (TLs), taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 millimeter (mm) from nadir. Median PFS was calculated using Kaplan-Meier method and its confidence interval (CI) using Brookmeyer-Crowley method.

Full results on the registry

What is this study about?

This study is for people who have advanced or metastatic breast cancer. This means the cancer has spread from where it started. Specifically, we're looking for breast cancer that has two particular features: it's 'HER2-low' and 'hormone receptor positive'. These are specific types of cells within the cancer that doctors identify with special tests.

The trial is testing a new drug called trastuzumab deruxtecan. This drug is designed to attack cancer cells that have the 'HER2-low' feature. We're comparing it to common chemotherapy treatments that your doctor would typically choose. The main things we want to learn are whether this new drug is more effective (for example, if it helps people live longer without their cancer getting worse, or helps them live longer overall) and if it has different side effects compared to standard chemotherapy.

Another important part of this study is understanding how the treatments and the cancer itself affect your daily life and well-being. We call this 'quality of life'. By comparing the new drug with standard chemotherapy, we hope to find a better treatment option for people with this specific type of advanced breast cancer who have already tried other hormone-based treatments.

Key takeaways

This study is for advanced, HER2-low, hormone receptor positive breast cancer.
It tests a new drug against standard chemotherapy.
Aims to see if the new drug improves life expectancy or slows cancer growth.
Also looking at how treatments affect quality of life.
You won't choose your treatment; it's decided randomly.
Participation involves regular clinic visits and health checks.

Who may be eligible?

To join this study, you need to be at least 18 years old. Your breast cancer must be advanced or have spread to other parts of your body, and it must be confirmed as 'HER2-low' and 'hormone receptor positive'. This will be checked using a recent sample of your cancer tissue.

You should not have received chemotherapy for your advanced breast cancer before. Also, your cancer should have progressed (grown or spread) after you've had at least two different hormone treatments, or if it progressed soon after starting a hormone treatment combined with another specific drug called a CDK4/6 inhibitor. You'll also need to be in generally good health, meaning your body organs like your liver, kidneys, and bone marrow are working well.

There are some reasons why you might not be able to join. For example, if you have certain lung conditions, serious heart problems, or if your cancer has spread to your brain or spinal cord in a way that's causing problems. You also can't have been in a previous study using trastuzumab deruxtecan or be in another drug study at the same time.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

Are you 18 years old or older?
Do you have advanced or metastatic breast cancer?
Has your doctor told you your cancer is 'HER2-low' and 'hormone receptor positive'?
Has your cancer progressed after at least two hormone treatments, or quickly after a hormone and CDK4/6 inhibitor treatment?
Have you NOT had chemotherapy for advanced breast cancer yet?
Are you generally well enough for a clinical trial?

Answer every question to see your result.

What does participation involve?

Taking part in this study means you would receive either the new drug (trastuzumab deruxtecan) or one of the standard chemotherapy options, which would be chosen by your doctor. You wouldn't get to choose which treatment you receive. You'll have regular visits to the clinic for your treatment and check-ups. During these visits, doctors will perform physical examinations, take blood and urine samples, and do scans to monitor your health and how the treatment is working against your cancer.

Your doctors will also ask you questions about how you are feeling and if you are experiencing any side effects. You might also be asked to fill out questionnaires about your quality of life. The exact number of visits and the total length of your participation will depend on how you respond to the treatment, but these types of trials usually involve regular appointments over several months, with continued follow-up for your health and the cancer's progress even after treatment stops.

Potential risks and benefits

Participating in this study might offer the potential benefit of receiving a new treatment that could be more effective than current standard options, or it could give you access to standard treatment delivered with very close monitoring. However, there are also potential risks, as all medical treatments can have side effects. Some side effects might be mild, while others could be serious. All possible side effects will be fully explained to you by the study team. You have the right to withdraw from the study at any time, for any reason, without it affecting your usual medical care.

Locations (293)

Some site locations are approximate. We're improving this — please verify with the trial team before travelling.

Research Site
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Scottsdale, United States
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Springdale, United States
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Duarte, United States
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Los Angeles, United States
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Aurora, United States
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Lakewood, United States
Research Site
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Washington D.C., United States
Research Site
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Jacksonville, United States
Research Site
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Kansas City, United States
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Louisville, United States
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Bethesda, United States
Research Site
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Boston, United States

Common questions

What does 'HER2-low' and 'hormone receptor positive' mean?

These are specific features of your cancer cells that doctors look for in tests. 'HER2-low' means your cancer cells have a small amount of a protein called HER2, and 'hormone receptor positive' means they use hormones to grow.

What is trastuzumab deruxtecan?

It's a new type of drug being tested. It's designed to target and kill cancer cells that have the 'HER2-low' feature.

Will I get the new drug or chemotherapy?

In this study, you will randomly receive either the new drug (trastuzumab deruxtecan) or a standard chemotherapy chosen by your doctor. You won't get to pick which one.

Why is this study important?

It helps us find out if the new drug works better than existing treatments for this specific type of breast cancer, in terms of affecting cancer growth, how long people live, and their quality of life.

Can I leave the study if I want to?

Yes, you can choose to leave the study at any time, for any reason. Your decision won't affect the medical care you receive.