For breast cancer researchers, one of the biggest goals of a clinical trial is to address the unmet needs of people living with advanced breast cancer. Advanced breast cancer is difficult to cure or control with treatment. The cancer may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body, i.e., bones, lungs, brain, or liver. Patients with advanced breast cancer need more treatment options.
For patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer, the initial standard of care treatment is a combination of a drug called a CDK4/6 inhibitor (drugs that seek to stop cancer cells from multiplying), and a hormone therapy (drugs that seek to keep the cells from getting the estrogen they need to grow). We’ve learned from clinical trials that these drugs may delay the growth of breast cancer, but eventually these treatments may stop being effective for some people.
“Regardless of the success of these drugs, inevitably resistance occurs for most patients,” says Erika Hamilton, M.D. “There is a large need for additional endocrine treatments in this second line space and beyond.” Dr. Hamilton is a medical oncologist, and Director of Breast Cancer Research and Executive Chair of the Breast Cancer Research Executive Committee at Sarah Cannon Research Institute Oncology Partners.
Vepdegestrant and the VERITAC-2 Clinical Trial
Dr. Hamilton is one of the lead study doctors for the VERITAC-2 clinical trial. VERITAC-2 is a phase 3 clinical trial evaluating vepdegestrant (ARV-471). Vepdegestrant is part of an emerging class of drugs called PROTAC protein degraders, that are designed to make use of the body’s natural disposal system to break down proteins that cause different diseases. Vepdegestrant is a PROTAC® protein degrader designed to specifically target and degrade the estrogen receptor (ER). Vepdegestrant is being co-developed by Arvinas and Pfizer.
VERITAC-2 is exploring if the investigational medication, vepdegestrant may work better and is safer than an approved therapy, fulvestrant, in patients with ER+/HER2- advanced breast cancer whose disease has worsened after treatment with a CDK4/6 inhibitor and endocrine therapy. Fulvestrant (a Selective Estrogen Receptor Degrader) is an approved therapy often used in second line for ER+ advanced breast cancer.
VERITAC-2 is a randomized, open label trial. This means participants will be randomly assigned to the study treatments but will know which treatment they are receiving. This study has two distinct treatment groups (also called treatment arms). One group receives a dose of fulvestrant given as an injection, while the other group receives vepdegestrant which is a tablet taken by mouth. There are no placebos (medications that do not contain active ingredients) in this study.
As Dr. Hamilton explains, what makes this potential new treatment option unique is how it is targets certain parts of cancer cells called estrogen receptors.
“Vepdegestrant degrades the estrogen receptor in a new way,” Dr. Hamilton says. “In the phase I clinical trials, this compound showed clinical activity among patients whose cancer has already progressed on CDK4/6 inhibitors, as well as other treatments.”
A Potential Treatment Option
In February of 2024, the FDA granted Fast-Track designation to Arvinas, Inc. and Pfizer for the development of vepdegestrant. Through the process of a fast track, the FDA determines if a potential new treatment fulfills a critical or unmet need for a serious condition. This has the potential to get new options to patients faster.
If successful, investigators hope that the VERITAC-2 clinical trial will lead to a potential treatment option for patients with ER+/HER2- advanced breast cancer, especially considering there are unmet needs with currently available therapies. For instance, one of the currently approved standards of care therapy, fulvestrant is given as an injection which can cause discomfort at the injection site. The chance to take a tablet by mouth may be appealing to many patients. Many clinical trials are studying potential therapies that patients can take orally (as a pill or tablet) for this reason.
Of course, innovative clinical trials like VERITAC-2 would not be possible without the tireless work of researchers and the dedication of the volunteers who participate. As Dr. Hamilton observes, joining clinical trials may give some patients additional options.
“I think the most important thing for patients to realize is how exciting clinical trials can be in this ER+ breast cancer space. Our field is changing so rapidly, and by enrolling in clinical trials, patients may gain access to potential innovative therapies that are currently being studied for safety and efficacy.”
Vepdegestrant is not currently approved for use, and the VERITAC-2 clinical trial is still enrolling at the time this blog is published.
Learn more about the VERITAC-2 trial.
Visit our clinical trials page to learn more about clinical trials and read about our other featured clinical trials.
Did you know? Komen has invested more than $250 million in 590 research grants and nearly 70 clinical trials focused on MBC.
Arvinas is a sponsor for the Spotlight on Clinical Trials series. Arvinas and Pfizer are the sponsors of VERITAC-2.
