A Study to Test Inavolisib Treatments in Participants With Early-Stage, PIK3CA-Mutated Breast Cancer

1. Why is this study needed?

Early-stage breast cancer is a cancer that forms in the cells of the breast but has not spread to other body parts. ER-positive cancer is a type of cancer that is influenced by oestrogen hormones. In the cells of this cancer, there are proteins called oestrogen receptors (ER) that interact with the hormone oestrogen. When oestrogen binds to these receptors, it can signal the cancer cells to grow. ER-positive breast cancer is often treated with hormone-blockers. Sometimes, the cancer cells change in a way that makes them harder to treat, which is why new treatments are being studied.

This study is testing inavolisib with standard treatments in early-stage breast cancer (ribociclib and letrozole) before surgery. The combinations are being developed to treat early-stage breast cancer that is ER-positive and has a change called a ‘PIK3CA-mutation’.

The combinations are experimental medicines. This means health authorities (like the U.S. Food and Drug Administration and European Medicines Agency) have not approved inavolisib combinations for early-stage, PIK3CA-mutated breast cancer.

This study is looking at how safe combinations of inavolisib and standard treatments are. It also looks at how well they work in people with early-stage, PIK3CA-mutated ER-positive breast cancer.

2. Who can take part in the study?

Women of at least 18 years of age with PIK3CA-mutated, early stage (Stage II-III), ER-positive breast cancer can take part in the study if their breast cancer does not have extra proteins called ‘HER2-receptors’ (which makes it ‘HER2-negative’ breast cancer).

Women may not be able to take part in this study if they need breast cancer surgery immediately, if they have already had breast cancer treatment, or if they have certain health conditions like diabetes, liver disease or lung disease. Women who are pregnant, or currently breastfeeding cannot take part in the study.

3. How does this study work?

Women will be screened to check if they are able to participate in the study. The screening period will take place up to 1 month before the start of treatment. Women who join this study will be placed in 1 of 3 groups (called ‘arms’) randomly and be given either:

• Arm A: inavolisib with ribociclib and letrozole for about 6 months
• Arm B: inavolisib with letrozole for about 1 month
• Arm C: ribociclib with letrozole for about 1 month 

After 1 month of treatment, women in Arms B and C will then be given the same treatment as Arm A (inavolisib with ribociclib and letrozole) for about 5 months.

The medicines in this study are taken as tablets (to be swallowed). Inavolisib and letrozole are taken once a day. Ribociclib will be taken daily for 21 days followed by 7 days off. Women who can get pregnant need to take medicine to stop ovulation (called an ‘LHRH agonist’). This will be for at least 14 days before starting the study medicines and during the study.

During the study, a small sample of breast cancer will be taken for testing (called a biopsy). After about 6 months of treatment, surgery will be done to remove any remaining breast cancer. If a participant cannot have surgery, another biopsy will be taken.

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 the first 3 months of this study, the doctor will see participants every 1 to 2 weeks to see if there are any unwanted effects and to see how well the treatment is working. From Month 4 of treatment, participants will see the study doctor each month. They will also have a phone call to check on their wellbeing between visits. Participants will have a follow-up visit about 1 month after their last dose of study treatment, during which the study doctor will check on the participant’s wellbeing. The total time of participation in the study will be about 8 months. It could last up to 11 months if the participant has a high level of sugar in the blood or is still recovering from surgery. 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 how safe the medicines are, are the number and seriousness of unwanted effects associated with a particular treatment or medicine.

Other key results measured in the study include:

• The number of participants with no detectable cancer left after treatment
• The number of participants with a reduction of their cancer after treatment
• Changes in Ki-67 - a marker tested in cancer cells used to see how fast cancer cells are growing
• How do unwanted effects from treatment affect participants’ daily lives and how this changes during the study
• Changes in the seriousness of unwanted effects and how they affect participants

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 inavolisib, ribociclib and letrozole
Participants may have unwanted effects of the medicines 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.

Participants will be told about the known unwanted effects and possible unwanted effects based on human and laboratory studies or knowledge of similar medicines. Known unwanted effects of inavolisib include wanting to throw up, throwing up, loose watery stools, rash, sore or swollen mouth or lips, and a high level of sugar in the blood. Known unwanted effects of ribociclib include feeling tired or weak, wanting to throw up, loose watery stools, fever, cough, changes in blood test results that check how well the liver is working, a low number of white blood cells in the body, and hair loss. Known unwanted effects of letrozole include sweating more than usual, pain in joints, hot flushes and feeling tired or weak.

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