A study to look at how well giredestrant works in people with estrogen receptor-positive human epidermal growth factor receptor 2 negative (ER+/HER2−) early breast cancer who may not put up with or do well on aromatase inhibitor drugs

1. Why is this study needed?

Early breast cancer is a condition where cancer cells grow in the breast but have not spread far beyond it. It is often linked to hormones like estrogen, which can fuel the growth of certain types of breast cancer. In this case, the cancer is estrogen receptor-positive (ER+). Also, it does not have a protein called human epidermal growth factor receptor 2 (HER2−). This can make cancer harder to treat. Treatments often include medicines that block hormones. However, some patients experience unwanted effects that make these treatments hard to put up with or do well on. This means the medicine is hard to endure or put up with. Not being able to put up with or take the medicine consistently can increase the risk of the cancer returning.

The goal of this study is to look at an oral treatment that may be more tolerable for patients.

This study is testing a medicine called giredestrant. It is being developed to treat ER+/HER2− early breast cancer.

Giredestrant is an experimental medicine. This means health authorities (like the U.S. Food and Drug Administration) have not approved giredestrant for the treatment of ER+/HER2− early breast cancer.

This study aims to explore how switching to giredestrant can help people with ER+/HER2− early breast cancer who could not put up with or do well on medicines called aromatase inhibitors. Giredestrant will be given daily for up to 4.5 years.

2. Who can take part in the study?

Women with early-stage breast cancer that is ER+/HER2− can take part in the study. They must be aged 18 years or older and postmenopausal (no periods for at least 12 months). Participants must have previously used aromatase inhibitors for at least 6 months. Three months of this treatment must be immediately before screening. Participants must also experience intolerable unwanted effects from this medicine. Lastly, they must meet other health and treatment-related criteria.

People with any of the following may not be able to take part in this study:

• Are taking certain medications
• Recent use of certain cancer treatments
• Have heart or liver problems
• Have certain infections
• Cannot swallow pills
• Are pregnant or currently breastfeeding

3. How does this study work?

People will be screened to check if they are able to take part in the study. The screening period will take place up to 36 days before the start of study treatment. After screening, people who meet all study criteria will have a 7-day treatment-free period.

Everyone who joins this study will be given giredestrant daily for up to 4.5 years.

This is an open-label study. This means everyone involved, including the participant and the study doctor, will know the study treatment the participant has been given.

During this study, the study doctor will see participants about once a month for the first 3 months. After the third month, the study doctor will see participants every 3 months for the rest of the treatment. The study doctor will see how well giredestrant is working. They will also check for any unwanted effects participants may have. During treatment, participants will have up to 23 clinic visits. After the first year of the study, the study doctor visits may be in person or through virtual telemedicine visits. This will be decided by the study doctor. Telemedicine visits are done remotely by telephone or video calls. Participants will have follow-up visits at least once a year for up to 2 years after completing giredestrant. Total time of participation in the study will be about 6.5 years. Participants have the right to stop study treatment and leave the study at any time, if they wish to do so.

4. What are the main results measured in this study?

The main result measured in this study is the number of participants who stop taking giredestrant. The number of participants who stop taking giredestrant for any reason at 12 months will be recorded. The number of unwanted effects reported during the study and how severe they are will also be recorded.

Other key results measured in the study include how giredestrant affects specific symptoms like joint pain, hot flashes, vaginal dryness, and sexual problems; the overall discomfort caused by the giredestrant at 6 and 12 months; and any changes in the participants' physical and daily functioning, and overall quality of life at 6 and 12 months.

5. Are there any risks or benefits in taking part in this study?

Taking part in the study may or may not make participants feel better. But the information collected in the study can help other people with similar health conditions in the future.

It may not be fully known at the time of the study how safe and how well the study treatment works. The study involves some risks to the participant. But these risks are generally not greater than those related to routine medical care or the natural progression of the health condition. People interested in taking part will be informed about the risks and benefits, as well as any additional procedures or tests they may need to undergo. All details of the study will be described in an informed consent document. This includes information about possible effects and other treatment options.

Risks associated with the study drug 
Participants may have unwanted effects of the drug used in this study. These unwanted effects can be mild to severe, even life-threatening. They can vary from person to person. During this study, participants will have regular check-ups to see if there are any unwanted effects.

Giredestrant
Participants will be told about the known unwanted effects of giredestrant. This includes possible unwanted effects based on human and laboratory studies or knowledge of similar medicines. Known unwanted effects include joint pain or stiffness, diarrhea, tiredness, muscle or bone pain, nausea, possible liver damage, and hot flashes.