Phase: Phase III
ClinicalTrials.gov ID number: NCT03734029
Sponsors of the trial: Daiichi Sankyo, Inc., and AstraZeneca
Who is the trial for?
The DESTINY-Breast04 trial is a phase III trial for people diagnosed with metastatic breast cancer with low HER2 levels or other stages of breast cancer with low HER2 levels that can’t be removed with surgery. For the purposes of this study, breast cancer with low HER2 levels means the cancer has a score of 2+ or 1+ on an immunohistochemistry (IHC) HER2 test or a negative fluorescence in situ hybridization (FISH) HER2 test. Breast cancer with these IHC or FISH scores would usually be considered HER2-negative breast cancer. Still, earlier studies have shown that the medicine being studied may help treat breast cancers with extremely low HER2 levels, which is why this larger study is being done.
The cancer also must have been previously treated with one or two chemotherapy regimens for people to be eligible for this study.
Doctors call cancer that can’t be completely removed with surgery unresectable. Metastatic breast cancer is breast cancer that has spread to parts of the body away from the breast, such as the bones or liver.
Why the trial is being done
The trial is looking to see whether fam-trastuzumab-deruxtecan-nxki offers better progression-free survival than your doctor’s choice of four chemotherapy medicines:
- Halaven (chemical name: eribulin)
- Gemzar (chemical name: gemcitabine)
- Taxol (chemical name: paclitaxel)
- Abraxane (chemical name: albumin-bound or nab-paclitaxel)
when treating metastatic breast cancer with low HER2 levels or other stages of disease with low HER2 levels that can’t be removed with surgery and has been previously treated with one or two chemotherapy regimens.
Progression-free survival is how long a person lives without the cancer growing.
Under the brand name Enhertu, fam-trastuzumab-deruxtecan-nxki is approved in the United States to treat metastatic HER2-positive breast cancer that has been treated with two or more anti-HER2 therapies or other stages of HER2-positive disease that can’t be removed with surgery.
The DESTINY-Breast04 trial is using the medicine to treat a different type of breast cancer than Enhertu is approved for, so when talking about the trial, the medicine is called by its chemical name: fam-trastuzumab-deruxtecan-nxki.
Fam-trastuzumab-deruxtecan-nxki is an antibody-drug conjugate made up of three parts:
- fam-trastuzumab: an anti-HER2 medicine that has the same basic structure as Herceptin (chemical name: trastuzumab)
- a topoisomerase I inhibitor chemotherapy medicine called DXd; topoisomerase I inhibitors work by interfering with the cancer cells’ ability to replicate; this type of chemotherapy is not typically used to treat HER2-positive breast cancer, so researchers believe it is less likely that the cancer will develop resistance to it
- a compound that links the fam-trastuzumab molecule to the topoisomerase I inhibitor molecule
The combination of the topoisomerase I inhibitor and the linking compound is called deruxtecan. The linking compound attaches (conjugates) the fam-trastuzumab to the topoisomerase I inhibitor chemotherapy.
Fam-trastuzumab-deruxtecan-nxki was designed to deliver the topoisomerase I inhibitor chemotherapy medicine to cancer cells in a targeted way by attaching the topoisomerase I inhibitor to the fam-trastuzumab. The fam-trastuzumab then carries the topoisomerase I inhibitor to the HER2-positive cancers cells. This way, the topoisomerase I inhibitor is less toxic to healthy cells and more effective in treating cancer cells.
Fam-trastuzumab-deruxtecan-nxki is given intravenously, which means the medicine is delivered directly into your bloodstream through an IV or a port.
Specific eligibility requirements
People are eligible for the DESTINY-Breast04 trial if:
- they are a legal adult in their country and have been diagnosed with metastatic breast cancer with low HER2 levels or other stages of disease with low HER2 levels that can’t be removed with surgery; for the purposes of this study, breast cancer with low HER2 levels means the cancer has a score of 2+ or 1+ on an IHC test or a negative FISH HER2 test
- the cancer has been previously been treated with one or two chemotherapy regimens
- the cancer is also hormone-receptor-positive and has grown while being treated with hormonal therapy or would no longer benefit from hormonal therapy
People are not eligible for the DESTINY-Breast04 trial if they:
- can’t be treated with Halaven, Gemzar, Taxol, or Abraxane
- have been diagnosed with breast cancer considered to have high levels of HER2 (IHC test score of 3)
- have been previously treated with any anti-HER2 therapy
- have a medical history of interstitial lung disease or pneumonia or are suspected to have interstitial lung disease or pneumonia; interstitial lung disease is a general term for disorders that cause inflammation and scarring in the lungs
- have brain metastases
- have spinal cord compression
Potential side effects of the treatment being studied
In earlier studies, the most commons side effects of fam-trastuzumab-deruxtecan-nxki were:
- low white blood cell counts
- hair loss
- low platelet counts
- decreased appetite
Fam-trastuzumab-deruxtecan-nxki also may cause serious side effects, including:
- Interstitial lung disease: Interstitial lung disease is a general term for disorders that cause inflammation and scarring in the lungs. The scarring makes lung tissue stiff, which makes it difficult to breathe. You will be closely monitored for signs of interstitial lung disease while being treated with fam-trastuzumab-deruxtecan-nxki. You must tell your doctor right away if you experience shortness of breath or have a dry cough.
- Heart problems: Fam-trastuzumab-deruxtecan-nxki may cause serious heart problems, including some that don’t have symptoms, such as reduced heart function, and some that do have symptoms, such as congestive heart failure. Symptoms to watch for include swelling of the ankles or legs, shortness of breath, cough, or weight gain of more than 5 pounds in less than 24 hours.
- Neutropenia: Neutrophils are a type of white blood cell. Neutropenia means you have low levels of neutrophils in your blood. When neutropenia is severe, even the normal bacteria in your mouth and digestive tract can cause serious illness.
Your doctor will monitor you for any serious side effects while you’re being treated with fam-trastuzumab-deruxtecan-nxki and may reduce your dose, delay your treatment or completely stop treatment if you do have serious side effects.
The DESTINY-Breast04 trial is being conducted at multiple sites in the United States and around the world. For a complete list of sites, visit https://clinicaltrials.gov/ct2/show/NCT03734029.
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