A trial to learn if camizestrant is safe and works better than the currently available treatments in people with ER+/HER2- early-stage breast cancer.

Trial Background

Current standard treatment for ER+/HER2- early-stage breast cancer includes surgery to remove the cancer, followed by endocrine therapy (ET). Some people also have chemotherapy, radiation therapy, or both. Abemaciclib is another anti-cancer drug that can be added to ET in patients at higher risk of their cancer coming back. But ET with or without abemaciclib may not work well enough for everyone in the long term and the cancer can return. The trial drug, camizestrant, is designed to work by blocking the effects of estrogen. Researchers think that treatment with camizestrant could work better than standard ET for preventing ER+/HER2- early-stage breast cancer from coming back.

Trial Design

This is a phase 3, randomized, and open-label trial. Phase 3 means that the trial treatment is being compared to a standard treatment in a large number of participants. Randomized means a computer program will randomly choose which treatment each participant will take. Open-label means each participant, as well as their doctors and trial staff, will know what treatment they are taking. Participants will receive trial treatment for 7 years and have follow-up visits for up to 3 more years. Participants will stop trial treatment sooner if their breast cancer comes back, a trial doctor decides the treatment is no longer helpful, they have an intolerable adverse event, they need to start a new cancer treatment, they do not want to continue participating, they become pregnant, or for other reasons.

Trial Population

This trial will include about 5,500 participants with ER+/HER2- early-stage breast cancer. Participants must have had surgery to remove their cancer and no more than 12 weeks of standard ET. Participants will have breast cancer with an “intermediate-high” or “high” risk of coming back.

Treatments and Procedures

All participants will take standard ET or camizestrant. Some of the participants will also take abemaciclib, if the trial doctors think it will help them.

All pre- and peri-menopausal female participants and male participants not receiving tamoxifen, will also be treated with an LHRH agonist. This is an injection that blocks the production of sex hormones by the ovaries and testicles, and may help the trial treatment work better. During the trial, the doctors will monitor the participants’ health by:

• Testing the participants’ blood
• Performing physical exams
• Checking the participants’ vital signs
• Getting scans when appropriate
• Asking the participants to fill out questionnaires about their health
• Testing the participants’ heart function using an electrocardiogram (ECG)

Ethical Considerations

All participants will help researchers learn more about camizestrant. The possible benefit for taking camizestrant is that it could work better than standard ET in preventing the cancer from coming back. But, it is also possible that camizestrant might not work as well as standard ET.

The most common risks when taking camizestrant are:

• Slowing of the heart rate
• Intermittent visual effects

There are other less common risks for camizestrant as well as risks related to standard ET, abemaciclib, and the procedures done in this trial. The trial doctor or staff will have more information on these risks, and the risks are also described on the drug labels.

The tests, procedures, and actions from the participants are needed to make sure the trial results are accurate.