ASCENT-05 Trial for Triple-Negative Breast Cancer
Trial Details
Overview: The ASCENT-05 trial is comparing the effectiveness and safety of Trodelvy (chemical name: sacituzumab govitecan-hziy) in combination with Keytruda (chemical name: pembrolizumab) after surgery to either Keytruda alone or Keytruda plus Xeloda (chemical name: capecitabine) in people diagnosed with early-stage, triple-negative breast cancer that have residual disease after surgery.
Phase: Phase III; Phase III trials compare the safety and effectiveness of a new treatment to the current standard of care. Phase III trials are usually large – some involve thousands of people – and are done at many places in the United States and around the world.
Number of people to enroll: 1,514
ClinicalTrials.gov ID number: NCT05633654
Sponsor of the trial: Gilead Sciences
Collaborator: Alliance Foundation Trials, LLC
Who is the trial for?
The ASCENT-05 trial is enrolling people diagnosed with stage I, stage II, and stage III (early-stage) triple-negative breast cancer who have what doctors call residual disease after neoadjuvant chemotherapy and surgery.
Triple-negative breast cancer is cancer that has no receptors for the hormones estrogen and progesterone, as well as no receptors for the HER2 protein. This limits the medicines that can be used to treat the cancer.
Treatments given to weaken and destroy cancer cells before surgery to remove the cancer are called neoadjuvant treatments.
One way doctors judge the effectiveness of neoadjuvant chemotherapy is to look at the tissue removed during surgery to see if any actively growing cancer cells are present. If no active cancer cells are present, doctors call it a pathologic complete response or pCR.
If there are cancer cells present in the tissue removed, this cancer is called residual disease.
Why is the trial being done?
The ASCENT-05 study is designed to see if treating the residual disease with Trodelvy and Keytruda offers better disease-free survival than doctors’ choice of either Keytruda alone or Keytruda plus Xeloda.
Disease-free survival is how long a person lives without the cancer coming back (recurrence).
Currently, Trodelvy is used to treat advanced-stage, hormone receptor-positive and hormone receptor-negative, HER2-negative breast cancer that has been previously treated. This study is looking to see if Trodelvy can help treat early-stage breast cancer.
Trodelvy is an immune targeted therapy medicine. It is made up of:
sacituzumab, a type of molecule called a monoclonal antibody, that targets the Trop-2 protein on the surface of cancer cells
SN-38, a topoisomerase I inhibitor chemotherapy medicine
a compound that links the sacituzumab to the SN-38
Doctors call Trodelvy an antibody-drug conjugate. The linking compound attaches (conjugates) the monoclonal antibody sacituzumab to the SN-38 chemotherapy.
Research has shown that the Trop-2 protein is found on the surface of about 90% of breast cancers. Sacituzumab, one of the compounds that makes up Trodelvy, targets the Trop-2 protein and attaches to it. SN-38 is the topoisomerase I inhibitor chemotherapy medicine part of Trodelvy. Like other chemotherapy medicines, it interferes with a cell’s ability to replicate. SN-38 isn’t a targeted medicine, which means it can affect healthy cells as well as cancer cells.
Trodelvy was designed to deliver the SN-38 chemotherapy to cancer cells in a targeted way by attaching the SN-38 to the sacituzumab. The sacituzumab then carries the SN-38 to the triple-negative cancer cells. This way, the SN-38 is less toxic to healthy cells and more effective in treating cancer cells.
Trodelvy is given intravenously, which means the medicine is delivered directly into your bloodstream through an IV or port.
Keytruda is a type of immunotherapy known as an immune checkpoint inhibitor. To start an immune system response to a foreign invader, the immune system has to be able to tell the difference between cells or substances that are “self” (part of you) vs. “non-self” (not part of you and possibly harmful). Your body’s cells have proteins on their surfaces or inside them that help the immune system recognize them as self.
Some of these proteins that help your immune system recognize self cells are called immune checkpoints. Cancer cells sometimes find ways to use these immune checkpoint proteins as a shield to avoid being identified and attacked by the immune system.
Immune system cells called T cells roam throughout the body looking for signs of disease or infection. When T cells meet another cell, they analyze certain proteins on the cell’s surface, which helps the T cell identify the cell. If the surface proteins signal that the cell is normal and healthy, the T cell leaves it alone. If the surface proteins suggest the cell is cancerous or unhealthy in another way, the T cell starts an attack against it. Once T cells start an attack, the immune system begins to make more specialized proteins that prevent this attack from damaging normal cells and tissues in the body. These specialized proteins that keep healthy cells and tissues safe are called immune checkpoints.
Immune checkpoint inhibitors target these immune checkpoint proteins and help the immune system recognize and attack cancer cells. Immune checkpoint inhibitors essentially take the brakes off the immune system by blocking checkpoint inhibitor proteins on cancer cells or on the T cells that respond to them.
For example, PD-1 is a checkpoint protein on T cells. PD-L1 is another checkpoint protein found on many healthy cells in the body. When PD-1 binds to PD-L1, it stops T cells from killing a cell. Some cancer cells have a lot of PD-L1 on their surface, which stops T cells from killing these cells. Keytruda stops PD-1 from binding to PD-L1 and allows T cells to attack the cancer cells.
Keytruda is given as an injection in a doctor's office.
Xeloda is chemotherapy medicine that is taken orally as a pill.
In the study, people will receive either:
Trodelvy, given on day one and day eight of a continuous 21-day treatment cycle, plus Keytruda given as an injection on day one of the 21-day cycle, for eight cycles, unless the cancer grows or unacceptable side effects develop
doctors’ choice of either Keytruda alone as an injection on day one of a 21-day cycle, for eight cycles, or Keytruda as an injection on day one of a 21-day cycle plus Xeloda twice a day on days one through 14 of the 21-day cycle, for eight cycles
Specific eligibility requirements
Adults are eligible for the ASCENT-05 study if they:
have been diagnosed with early-stage, triple-negative breast cancer and have residual disease in the breast or lymph nodes after neoadjuvant chemotherapy and surgery
have received appropriate radiation therapy and have recovered from any side effects before joining the study
People are not eligible for the ASCENT-05 study if they:
have been diagnosed with stage IV/metastatic breast cancer or have been diagnosed with a previous primary breast cancer
have a BRCA mutation
have received any anti-HER2 medicine
have previously received another type of immunotherapy medicine
have been diagnosed with recurrent breast cancer after neoadjuvant chemotherapy and surgery
have received a treatment containing a topoisomerase inhibitor
Possible side effects of Trodelvy
The most common side effects caused by Trodelvy are:
Possible side effects of Keytruda
The most common side effects of Keytruda are:
Possible side effects of Xeloda
The most common side effects of Xeloda are:
irregular periods — this can include temporary cessation (usually resume after medication is completed) or permanent cessation of menstrual periods depending on your age and other factors
Study locations
The ASCENT-05 study is being conducted at 11 sites across the United States:
Huntsville, AL
Glendale, AZ
Los Angeles, CA
Redlands, CA
Atlanta, GA
Marietta, GA
Bethesda, MD
East Brunswick, NJ
Florham Park, NJ
Sioux Falls, SD
Knoxville, TN
For a complete list of sites, visit: https://clinicaltrials.gov/ct2/show/NCT05633654
For more information or to enroll
Visit the Gilead ASCENT-05 trial website.
— Last updated on September 16, 2024 at 1:00 PM