DS8201-A-U301, Phase 3, HER2-Positive Breast cancer
Research type
Research Study
Full title
A PHASE 3, MULTICENTER, RANDOMIZED, OPEN-LABEL, ACTIVE-CONTROLLED STUDY OF DS-8201A, AN ANTI-HER2-ANTIBODY DRUG CONJUGATE, VERSUS TREATMENT OF INVESTIGATOR’S CHOICE FOR HER2-POSITIVE, UNRESECTABLE AND/OR METASTATIC BREAST CANCER SUBJECTS PRETREATED WITH PRIOR STANDARD OF CARE HER2 THERAPIES, INCLUDING T-DM1
IRAS ID
251935
Contact name
Peter Schmid
Contact email
Sponsor organisation
Daiichi Sankyo, Inc
Eudract number
2018-000221-31
Clinicaltrials.gov Identifier
127553, IND
Duration of Study in the UK
3 years, 3 months, 1 days
Research summary
Breast cancer remains the most common cancer and the second leading cause of cancer mortality in women globally. In 2015, there were 2.4 million new cancer cases leading to 523,000 deaths worldwide. Approximately 20% of breast cancer cases test positive for a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. HER2-positive breast cancers tend to be more aggressive and have worse outcomes than other types of breast cancer. This study involves research of a potential new drug, DS-8201a, that is being developed for cancer treatment. It will compare the activity of DS-8201a in participants with HER2-positive, versus 2 investigator’s choice options that are currently part of guideline recommendations for this line of therapy.
The following drugs have been selected as the comparator treatments in this study:
• Trastuzumab/capecitabine or
• Lapatinib/capecitabine
The comparator drugs are approved in the United Kingdom for HER2 positive breast cancer.
Depending on which treatment group participants are in, they will take DS-8201a or the other treatment (trastuzumab/capecitabine or lapatinib/capecitabine).
The study comprises of a screening part (up to 28 days), a Treatment period and a Follow-up period.
It is expected that about 600 patients will participate in approximately 160 sites around the world. In the UK it is expected that the study will take place in 11 sites.Lay summary of study results: The study was a Phase 3, open-label, randomized trial with about 600 participants who had HER2-positive breast cancer that had spread and were previously treated with T-DM1. Participants were randomly assigned in a 2:1 ratio to receive either trastuzumab deruxtecan (T-DXd) or treatment chosen by their doctor, which included trastuzumab/capecitabine or lapatinib/capecitabine. The T-DXd dose was 5.4 mg/kg every 3 weeks, given by infusion. Participants stayed in their assigned group and did not switch treatments. The study was not blinded to participants or doctors because the treatments were different, but the main results were reviewed by experts who did not know which treatment the participants got. The study included many safety and effectiveness checks, and some changes were made during the study, including adjustments due to COVID-19. All participants signed consent forms before joining. The study ended with all participants stopping treatment, mostly because their disease got worse.
The study treated participants with HER2-positive breast cancer, a type of cancer that grows due to a protein called HER2. The treatment used was trastuzumab deruxtecan (T-DXd, DS-8201a, Enhertu®). This medicine is an antibody-drug conjugate, which means it combines an antibody that specifically targets the HER2 protein on cancer cells with a chemotherapy drug. The antibody guides the chemotherapy drug directly to the cancer cells, helping to kill them while limiting damage to normal cells.
The main question the researchers wanted to answer in this study was:
How much longer did trastuzumab deruxtecan (T-DXd) help participants live without their breast cancer getting worse compared to the usual treatments chosen by doctors?
This trial started in September 06, 2018 and ended in December 23, 2025. The study lasted for over 7 years.
The study had 608 participants from 15 countries including the US, Japan, France, Italy, Spain, Turkey, South Korea, Brazil, UK, Germany, Australia, Israel, Greece, Belgium, and Czech Republic. Most participants were women (over 99%), with only 5 men. The median age was about 54 years, with most participants between 40 and 65 years old. The participants had breast cancer that was HER2-positive and had spread or could not be removed by surgery. They had all been treated before with a specific medicine called T-DM1 and showed cancer growth after that treatment. Participants had to be adults, able to understand and agree to the study, have at least one measurable tumor, and have good enough health in terms of heart, liver, kidneys, and bone marrow. They also had to have a good performance status, meaning they could take care of themselves and were not too sick. People were not allowed in the study if they had serious heart problems, lung disease, active brain cancer symptoms, infections like HIV or hepatitis, or if they were pregnant or breastfeeding.
The study found that the medicine called T-DXd helped participants with a certain kind of breast cancer live longer without the cancer getting worse. Participants who took T-DXd lived about 18 months without the cancer growing, compared to about 7 months for those who got other treatments. Also, more participants lived longer overall with T-DXd — about 39 months compared to 27 months with other treatments. The medicine also helped shrink the cancer more often and for a longer time. Participants who took T-DXd felt better for longer, especially with less pain.
During this study, participants treated with trastuzumab deruxtecan (T-DXd) experienced some side effects. Most side effects were manageable with treatment changes or medicine. Serious side effects were more common with T-DXd than the other treatments. Some participants had to stop treatment because of side effects, mainly due to a lung problem called interstitial lung disease (ILD), which affected 35 participants.
This study helped researchers learn that trastuzumab deruxtecan (T-DXd) worked better than other treatments for patients with HER2-positive metastatic breast cancer who had been treated before with T-DM1. It showed that T-DXd helped patients live longer without the cancer getting worse and also helped them live longer overall. The study also showed that patients' quality of life was better maintained with T-DXd. Researchers learned about the safety of T-DXd and how to manage side effects like lung problems. This study plans to help doctors use T-DXd as a good treatment option and to do more studies on how it works and how to make it safer.REC name
London - London Bridge Research Ethics Committee
REC reference
18/LO/1768
Date of REC Opinion
7 Feb 2019
REC opinion
Further Information Favourable Opinion