A study to look at how well giredestrant works in people with Stage 1, Grade 1 endometrial cancer, how safe giredestrant is and how the body processes it

1. Why is this study needed?

Endometrial cancer is a type of cancer that starts in the lining of the uterus, which is called the endometrium. If the cancer is only in the uterus, it is called Stage 1. When the cancer cells look more like normal cells and grow slowly, it is called Grade 1. Stage 1, Grade 1 endometrial cancer is usually low-risk. Treatment usually includes surgery to remove the uterus (hysterectomy). But some women may choose hormone medicine instead if they want to have children later or are not suitable for surgery. There is a need for better hormone treatments for people with endometrial cancer.

This study is testing a medicine called giredestrant. It is being developed to treat Stage 1, Grade 1 endometrial cancer.

Giredestrant is an experimental medicine. This means health authorities (like the U.S. Food and Drug Administration and European Medicines Agency) have not approved giredestrant for the treatment of endometrial cancer.

This study aims to test how safe giredestrant is, how well it works, and to understand what happens to giredestrant once it is in the body.

2. Who can take part in the study?

Women who are 18 years or older can take part in the study if they have Stage 1, Grade 1 endometrial cancer. Participants must be willing to receive the study treatment for 6 months before making a decision about surgery. They must also be willing to have small samples of tissue (biopsies) collected from the endometrium for testing throughout the study.

People may not be able to take part in this study if they have previously been treated for endometrial cancer, or have had certain cancer treatments within a specific timeframe before the study. Other reasons may include having conditions that affect the digestive system or liver, certain infections, or not being able to swallow pills.

People who are pregnant, or currently breastfeeding cannot take part in the study.

3. How does this study work?

People will be screened to check if they are able to participate in the study. The screening period will take place from 28 days before the start of treatment.

Everyone who joins this study will be given giredestrant as a pill (to be swallowed) once every day over 6 months, in 28-day treatment periods (called treatment ‘cycles’) until they have completed 6 treatment cycles. After 6 treatment cycles, the participant and the study doctor will decide on the next steps. They can either continue with the study treatment for up to 18 more treatment cycles or switch to a standard treatment (such as surgery or taking medication outside of the study).

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 at the start of each treatment cycle. They will see how well the treatment is working and any unwanted effects participants may have. These hospital visits will include taking a small sample of endometrial cells (called a ‘biopsy’) at the start of the study, and again at months 3 and 6. Participants will have follow-up visits after 1 month of completing the study treatment and then every 6 months. During these visits, the study doctor will check on the participant’s well being. Total time of participation in the study will be about 8 months to more than 2 years (26 months). 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 results measured in the study to assess if the medicine has worked are

• The number of participants who have a decrease in cancer cells or an increase in normal cells lining the uterus (known as ‘regression’) in a biopsy of their endometrium taken at month 6 compared with the start of the trial
• The number and seriousness of any unwanted effects

Other key results measured in the study include

• How many participants have no cancer or abnormal cell growth in their biopsy at month 6?
• How much time is there between when the cancer starts to get better and when it gets worse?
• How much time is there between starting the study treatment and when the cancer starts to get better?
• How much time is there between starting the study treatment and the participant’s cancer getting worse?

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 options of treatment.

Risks associated with the study medicine

Participants may have unwanted effects of the medicine used in this study. These unwanted effects can be mild to severe, even life-threatening, and 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, and possible unwanted effects based on human and laboratory studies or knowledge of similar medicines. Known unwanted effects include pain in joints, loose, watery [and more frequent] stools, feeling tired or weak, muscle or bone pain, wanting to throw up, and high levels of certain substances in blood (liver enzymes).

Giredestrant will be given as a pill (given by mouth). Participants will be told about any known unwanted effects of swallowing pills.

The study medicine may be harmful to an unborn baby. Women must take precautions to avoid exposing an unborn baby to the study treatment.