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Study comparing datopotamab deruxtecan with or without durvalumab to chemotherapy with pembrolizumab for patients with triple-negative breast cancer

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What is this trial about?

A plain-language summary of the goals, design and what participants do

This study involves patients with triple-negative breast cancer that has spread to other parts of the body or has come back in a way that cannot be removed by surgery. Triple-negative breast cancer is a type of breast cancer that does not have certain receptors on the cancer cells, which makes it different from other breast cancer types. The study will use several different medications. The main medication being tested is datopotamab deruxtecan, which has the code name DS-1062a. This medication may be given alone or together with another medication called durvalumab, which is also known as IMFINZI. These treatments will be compared to a combination of pembrolizumab plus one of the following chemotherapy medications chosen by the doctor: paclitaxel, nab-paclitaxel, or a combination of gemcitabine and carboplatin. All participants in the study must have cancer that tests positive for a marker called PD-L1, which is a protein found on some cancer cells. Some participants may also receive other medications such as infliximab or mycophenolate mofetil as supportive treatments.

The purpose of this study is to find out if treatment with datopotamab deruxtecan combined with durvalumab works better than the standard chemotherapy combinations with pembrolizumab in stopping the cancer from getting worse or spreading further. The study will measure how long patients live without their cancer getting worse, and will also look at how long patients live overall, how many patients respond to treatment, and how long those responses last. The study will also examine the safety of these treatments and how they affect quality of life and symptoms.

Participants will be randomly assigned to receive either datopotamab deruxtecan with or without durvalumab, or one of the chemotherapy options combined with pembrolizumab. All medications in this study are given through a vein as an infusion. During the study, participants will have regular check-ups that include scans to see how the cancer is responding to treatment. The doctors will also monitor for any side effects and collect information about how participants are feeling. Blood samples will be taken to measure the levels of medication in the body and to check how the immune system responds to the treatment. The study will continue until 2029, and participants will be followed even after they stop taking the study medication to see how they are doing.

The research process

The trial runs in 9 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Random assignment to treatment group
Upon joining the study, you will be randomly assigned to one of three treatment groups. This process is similar to flipping a coin and determines which combination of medications you will receive.
The three possible treatment groups are: datopotamab deruxtecan combined with durvalumab, datopotamab deruxtecan alone, or a chemotherapy option chosen by your doctor (either paclitaxel, paclitaxel albumin-bound, or gemcitabine plus carboplatin) combined with pembrolizumab.
Step 2
Provision of tumor tissue sample
You will need to provide a tumor tissue sample that has been preserved in a special way. This sample should be collected from your current tumor that has spread or returned.
If a recent sample is not available, an older stored sample may be used. However, if the older sample is from an earlier stage of your breast cancer, it must have been collected within 3 years before you joined the study.
The sample will be sent to a specialized laboratory to test for a protein called PD-L1. This test helps determine if you are eligible to continue in the study.
Step 3
Treatment administration - Group 1: Datopotamab deruxtecan with durvalumab
If you are assigned to this group, you will receive two medications given through a vein in your arm.
Datopotamab deruxtecan will be administered as an intravenous infusion, which means the medication is slowly delivered into your vein over a period of time. The specific dose, frequency, and duration will be determined by the study protocol.
Durvalumab will also be given as an intravenous infusion. The medication is delivered into your vein at the treatment visits.
Both medications will be given on scheduled treatment days according to the study plan. The treatment will continue until your disease progresses, you experience unacceptable side effects, or you decide to stop treatment.
Step 4
Treatment administration - Group 2: Datopotamab deruxtecan alone
If you are assigned to this group, you will receive one medication given through a vein in your arm.
Datopotamab deruxtecan will be administered as an intravenous infusion. The medication is slowly delivered into your vein over a period of time.
The medication will be given on scheduled treatment days according to the study plan. The treatment will continue until your disease progresses, you experience unacceptable side effects, or you decide to stop treatment.
Step 5
Treatment administration - Group 3: Chemotherapy with pembrolizumab
If you are assigned to this group, you will receive chemotherapy chosen by your doctor along with an additional medication.
Your doctor will select one of the following chemotherapy options based on what is most suitable for you:
Paclitaxel given as an intravenous infusion, or
Paclitaxel albumin-bound given as an intravenous infusion, or
Gemcitabine combined with carboplatin, both given as intravenous infusions.
In addition to the chemotherapy, you will receive pembrolizumab as an intravenous infusion.
All medications will be given on scheduled treatment days according to the study plan. The treatment will continue until your disease progresses, you experience unacceptable side effects, or you decide to stop treatment.
Step 6
Regular monitoring visits during treatment
Throughout the treatment period, you will attend regular visits for monitoring.
During these visits, imaging scans will be performed to assess how your tumor is responding to treatment. These scans will be reviewed by both your doctor and by independent medical experts who are not directly involved in your care.
Blood samples will be collected to monitor your organ function and bone marrow health, and to measure the levels of study medications in your blood.
Your overall health and any side effects you experience will be assessed at each visit.
You may be asked to complete questionnaires about your symptoms, including breast symptoms, arm symptoms, pain, physical functioning, and overall quality of life.
Step 7
Assessment of treatment response
The effectiveness of your treatment will be measured by tracking the time until your disease progresses or worsens.
Your doctor will use imaging scans and established criteria to determine if your tumor has shrunk, stayed the same size, or grown.
Independent medical experts will also review your scans separately to confirm the findings.
Other measures include whether your tumor responds to treatment, how long any response lasts, and your overall survival.
Step 8
Continuation of treatment
You will continue receiving your assigned treatment for as long as it is beneficial and tolerable.
Treatment will continue until one of the following occurs: your disease progresses, you experience side effects that are too severe to continue, you decide to withdraw from the study, or your doctor determines it is no longer in your best interest to continue.
Step 9
Follow-up after treatment discontinuation
If you stop receiving the study treatment, you will continue to be followed for your health status.
Information will be collected about any additional cancer treatments you receive after stopping the study treatment.
Long-term survival information will be collected throughout the study period, which is expected to continue until November 2029.

Who can join the trial?

11 criteria

You must have triple-negative breast cancer, which is a type of breast cancer that lacks three specific receptors, confirmed by examination of tissue under a microscope
Your cancer must have come back in a way that cannot be removed by surgery, or it must have spread to other parts of your body
Your cancer must be PD-L1 positive, which means your cancer cells have a specific protein marker on their surface. This will be tested in a central laboratory using a score called CPS that must be 10 or higher
Your general health and ability to carry out daily activities must be good, rated as 0 or 1 on a scale called ECOG, meaning you are fully active or able to do light work
You must be able to provide a tissue sample from your cancer. This can be a new sample from the cancer that has spread or come back, or an older sample if it was collected within 3 years before joining the study
You must not have received chemotherapy or other cancer treatments for cancer that has spread or come back. If your cancer came back after earlier treatment, at least 6 months must have passed since you finished that treatment
You must be able to receive one of the following chemotherapy treatments: paclitaxel, nab-paclitaxel, or a combination of gemcitabine and carboplatin
Your cancer must be measurable, meaning doctors can see and measure at least one tumor on scans according to standard measurement guidelines
Your bone marrow, which makes blood cells, and your organs such as liver and kidneys must be working well enough based on blood test results
If you are able to have children, you must agree to use reliable birth control methods as specified by the study
Both men and women can participate in this study

Who cannot join the trial?

12 criteria

You have active brain metastases, which means cancer has spread to your brain and is currently growing or causing symptoms
You have received previous treatment with certain types of cancer drugs called topoisomerase I inhibitors, which are medications that work by blocking a specific enzyme that helps cancer cells divide
You have a history of non-infectious pneumonitis, which is inflammation of the lungs not caused by infection, that required treatment with steroids (anti-inflammatory medications)
You have interstitial lung disease, which is scarring or inflammation of the tissue between the air sacs in your lungs
You have severe heart problems, including recent heart attack, unstable chest pain, or heart failure that is not well controlled
You have an active infection requiring treatment with antibiotics or other medications
You have another active cancer besides breast cancer, except for certain skin cancers or early-stage cancers that have been completely removed
You have an autoimmune disease, which is a condition where your immune system attacks your own body, that requires ongoing treatment with medications that suppress your immune system
You are pregnant or breastfeeding
You have a known severe allergic reaction to any of the study medications or their ingredients
You have received a live vaccine within 30 days before starting the study treatment
You have severe problems with your liver function or kidney function based on blood test results

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Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

Responsive
Institut De Cancerologie De Lorraine
Vandoeuvre Les Nancy, France
Responsive
Istituto Europeo Di Oncologia S.r.l.
Milan, Italy
Responsive
Istituto Oncologico Veneto
Padua, Italy

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Investigated drugs

Datopotamab Deruxtecan
is a targeted cancer medication that works by delivering chemotherapy directly to cancer cells. It is designed to attach to specific proteins on the surface of cancer cells and release a cell-killing medicine inside them.
Durvalumab
is an immunotherapy medication that helps your immune system fight cancer. It works by blocking a protein that prevents immune cells from attacking cancer cells, allowing your body's natural defenses to better recognize and destroy cancer.
Paclitaxel
is a chemotherapy medication that stops cancer cells from dividing and growing. It works by interfering with the structures inside cells that help them divide.
Nab-paclitaxel
is a form of chemotherapy similar to paclitaxel but attached to small protein particles. This formulation may help the medication reach cancer cells more effectively and can have different side effects than regular paclitaxel.
Gemcitabine
is a chemotherapy medication that interferes with the building blocks cancer cells need to grow and multiply. It helps slow down or stop the growth of cancer cells.
Carboplatin
is a chemotherapy medication that damages the genetic material inside cancer cells, preventing them from growing and dividing. It is often used in combination with other cancer medications.

Pembrolizumab

What is already known about the treatment

Datopotamab Deruxtecan
Datopotamab Deruxtecan, also known as Dato-DXd, is an investigational cancer medication currently being studied in clinical trials for the treatment of triple-negative breast cancer. It is administered intravenously, meaning it is given directly into a vein through an injection or infusion. This medication belongs to a class of drugs called antibody-drug conjugates, which work by combining a targeted antibody that finds cancer cells with a powerful chemotherapy drug that kills them; specifically, it attaches to a protein called TROP2 found on the surface of many cancer cells and delivers the chemotherapy directly into these cells, minimizing damage to healthy tissue. In this clinical trial, it is being tested alone or in combination with another immunotherapy drug called durvalumab to see if it works better than standard chemotherapy treatments for patients with advanced triple-negative breast cancer that cannot be removed by surgery.
Durvalumab
Durvalumab is an immunotherapy medication that is already approved for certain types of cancer and is being studied in combination with datopotamab deruxtecan for triple-negative breast cancer. It is given intravenously through an injection into a vein, typically administered in a hospital or clinic setting. This medication works by blocking a protein called PD-L1 on cancer cells, which normally helps tumors hide from the immune system; by blocking this protein, durvalumab allows the body's own immune system to recognize and attack cancer cells more effectively. It belongs to a class of drugs known as immune checkpoint inhibitors, which have revolutionized cancer treatment by helping the immune system fight cancer.
Pembrolizumab
Pembrolizumab is an established immunotherapy drug that is already approved for various cancers, including some types of breast cancer, and serves as part of the comparison treatment in this clinical trial. It is administered intravenously, meaning it is given through an injection directly into a vein, usually in a medical facility. This medication works by blocking a protein called PD-1 on immune cells, which prevents cancer cells from turning off the immune response; by blocking this protein, pembrolizumab helps the body's immune system recognize and destroy cancer cells more effectively. It belongs to the immune checkpoint inhibitor class of medications and is being used in combination with standard chemotherapy drugs as the control treatment to compare against the experimental therapy.

Investigated diseases

Triple-negative Breast Cancer – Triple-negative breast cancer is a type of breast cancer where the cancer cells test negative for three specific receptors: estrogen receptors, progesterone receptors, and HER2 protein. This means the cancer does not respond to hormonal therapy or drugs that target HER2 protein. The disease can occur in breast tissue and may spread to nearby lymph nodes or other parts of the body. When the cancer spreads beyond the breast to distant organs, it is called metastatic breast cancer. Locally recurrent inoperable triple-negative breast cancer refers to cancer that has come back in the breast area or nearby tissues and cannot be removed by surgery. This type of breast cancer tends to grow and spread more quickly than other forms of breast cancer.