Despite important advances in breast cancer treatment, the disease can still find ways to outsmart even the best therapies. People living with HER2-positive metastatic breast cancer (HER2+ MBC) often respond well to treatments at first, with tumors shrinking or slowing down, but the effectiveness of these drugs doesn’t always last. Through the EmpowHER-303 clinical trial (NCT06435429), researchers are shining a spotlight on a potential new treatment option, zanidatamab, a potent bispecific drug, or drug that can attach to two different targets at the same time, for the treatment of patients with HER2+ MBC.
Over time, cancer cells can grow again, even during treatment. For those patients with HER2+ MBC whose cancer progresses on trastuzumab deruxtecan (T-DXd), none of the currently approved treatment options were tested in clinical trials in patients who had previously received T-DXd treatment. The EmpowHER-303 clinical trial is exploring a potential new treatment option for patients with HER2+ MBC compared to this regimen.
“This particular trial is investigating a potential new treatment option called zanidatamab, for patients whose cancer has progressed on trastuzumab deruxtecan,” says Sara Tolaney, M.D., M.P.H. Dr. Tolaney is Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, and a Principal Investigator and Steering Committee member of the EmpowHER-303 trial.
Zanidatamab and the EmpowHER-303 Clinical Trial
EmpowHER-303 is a phase 3, open-label study evaluating the effectiveness and safety of zanidatamab in combination with chemotherapy compared to trastuzumab plus chemotherapy in patients with HER2+ MBC.
The main goal of the EmpowHER-303 study is to determine whether zanidatamab offers improved outcomes in terms of progression-free survival and overall survival compared to trastuzumab plus physician’s choice chemotherapy and may provide a new treatment option for patients.
“This trial is taking patients who have progressed on at least two HER2-directed therapies, one of which must have been T-DXd, if they were a candidate for T-DXd,” Dr. Tolaney explains. “Then they are randomized to receive chemotherapy of physicians’ choice with trastuzumab or chemotherapy of physicians choice with zanidatamab.”
Participants of the EmpowHER-303 study must be 18 or older and have had disease progression or trouble tolerating prior treatment with T-DXd. The trial is being conducted across approximately 170 sites worldwide, aiming to enroll approximately 550 participants. As Dr. Tolaney notes, one of the key goals of this study is to recruit participants across the globe that reflect the diversity of the breast cancer community. “I think that’s really important because we really want to understand how potential new drugs work in all patients that come from different backgrounds, not just race or ethnicity, but also different socioeconomic backgrounds,” she explains. “And we want to make sure all patients have access to treatment, so having good global representation is critical.”
Breaking Down the Science
While targeted treatments help many patients at first, cancers may eventually stop responding to these treatments. For example, trastuzumab works by attaching to one specific spot on the HER2 receptor — a protein that helps cancer cells grow and divide. This blocks some of the growth signals, slowing the cancer down.
Zanidatamab attaches to two different parts of the HER2 receptor instead of just one. This double binding may make it harder for cancer cells to keep growing. This could help the immune system better recognize these cells and destroy them.
“Zanidatamab binds to two different places on HER2, and by doing this, it causes differences in how it shuts down HER2 signaling,” Dr. Tolaney explains. “It not only shuts down the signal from HER2 because it’s binding to two different places, but it also causes this clustering of the HER2 receptor on the cell surface, which then can shut down the signaling more potently.”
A Need for More Tolerable Treatment Options
Treatment resistance is just one piece of the puzzle, and researchers are also seeking more tolerable treatment options. People living with MBC in particular need effective treatments with manageable side effects. The side effects of zanidatamab, similar to other treatments, include fatigue, diarrhea, flu-like symptoms and a low risk of heart toxicity. While zanidatamab may cause side effects, the patient’s care team can provide certain treatments that may help with these effects.
The EmpowHER-303 study continues to investigate the possibilities of this potential new drug and how it might benefit those living with HER2+ MBC who are seeking additional treatment options.
“It’s exciting because we can see that drug development is really improving with our technologies and we are figuring out new ways to shut down a potent signal that drives cancer growth,” Dr. Tolaney says.
Learn more about the EmpowHER-303 clinical trial.
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Did you know? Komen has invested more than $250 million in 590 research grants and nearly 70 clinical trials focused on MBC.
