NU 23B05 for Patients with ER-Positive/HER2-Negative Advanced or Metastatic Breast Cancer

Breast cancer is not only the leading cause of cancer in women, but also the leading cause of cancer deaths in women. Estrogen receptor-positive and HER2-negative (ER+/HER2-) breast cancer is the most widespread breast cancer subtype. Endocrine therapy is the main treatment given, but due to the diverse nature of the disease, development of resistance to this treatment, when the drug treatment is not working well anymore, is very common in individuals with metastatic cancer. “Metastatic” means that the cancer has spread in the body away from the original tumor site.

There remains an unmet need for more effective therapies for individuals with ER+/HER2-, metastatic breast cancer. Over the last decade, combining targeted therapy with endocrine drugs has proven more effective than treatment with an endocrine drug alone, particularly after disease progression. Instead of general cleanup (like traditional chemotherapy that attacks all fast-growing cells, healthy or not), targeted therapies are designed to recognize and interfere with specific features or signals within the cancer cells that allow them to thrive. “Disease progression” means that the cancer has gotten worse.

With the approval of a drug called elacestrant, specifically for individuals with endocrine- resistant, ESR-mutated, ER+/HER2, metastatic breast cancer, an important question is whether the effectiveness of this drug can be made better (enhanced) by combining it with a targeted drug such as a CDK 4/6 inhibitor. CDK4/6 is a protein that is involved in cell growth. A drug that could stop or slow down (inhibitor) this activity could also affect cancer cell growth.

Because CDK4/6 inhibitors are often the first treatment used for metastatic cancer, we don't know enough about whether they still work after the cancer gets worse in people who have already taken them.

The purpose of this study is to see whether the effectiveness of the drug elacestrant can be increased by combining it with a targeted drug such as a CDK4/6 inhibitor to treat participants with ER+/HER2- or metastatic breast cancer with previous exposure to a CDK4/6 inhibitor.

The U.S. Food and Drug Administration (FDA) has approved elacestrant for postmenopausal women or adult men with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. CDK4/6 inhibitors are a class of medicines used to treat certain types of hormone receptor-positive, HER2-negative breast cancer. Abemaciclib, palbociclib and ribociclib are CDK4/6 inhibitors that have been approved by the FDA for the treatment of some metastatic breast cancers. The FDA has not yet approved the combination of elacestrant and the CDK4/6 inhibitors to be used together for treatment, which is the research purpose for this study.

In order to participate you must meet the following criteria:

• Have histologically or cytologically confirmed ER-positive and HER2- negative breast cancer and a confirmed ESR1 mutation.
• Have received 1-2 prior endocrine therapies, including a CDK4/6 inhibitor in the metastatic disease setting.

You will be excluded from the study if any of the following criteria apply to you:

• Have received prior elacestrant.
• Have had chemotherapy ≤ 28 days prior to registration, or radiotherapy ≤ 14 days prior to registration.
• Have taken steroid therapy or any other immunosuppressive therapy within 7 days of first dose prior to trial treatment.
• Have brain metastases (some exceptions may be possible).

This is a partial list of eligibility requirements. To inquire about your eligibility, please call the contact number provided. If you wish to inquire via email, please include the title of the study in your message.