A Phase II Study Evaluating the Efficacy and Safety of Inavolisib Plus Ribociclib Plus Fulvestrant Versus Placebo Plus Ribociclib Plus Fulvestrant in Participants With Advanced Breast Cancer

To join this study, people must have breast cancer that has spread to other parts of the body or is locally advanced and can't be removed by surgery or treated with radiation. Their cancer must also be hormone receptor-positive and 'HER2-negative', meaning it doesn't have too much of a protein called HER2. Crucially, the cancer must have not responded to or have grown worse during or within 12 months of finishing previous hormone therapy, like an aromatase inhibitor or tamoxifen. They also can't have received any other treatments for their advanced cancer yet.

Another important requirement is a specific genetic test on the cancer tissue. The cancer must NOT have a particular change called a 'PIK3CA mutation' BUT it must show a loss of a specific part of chromosome 8 (called 'chr8p loss'). The cancer also needs to be measurable, meaning doctors can see and track its size. People with certain types of breast cancer, like metaplastic breast cancer, cannot join.

There are also some health conditions that would prevent someone from joining. For example, people shouldn't have had radiation therapy in the two weeks before starting the study. Individuals with type 1 diabetes or type 2 diabetes that needs ongoing systemic treatment, or certain untreated brain metastases, would not be able to participate. The study is open to both men and women, aged 18 or older.

If you decide to take part in this study, you would be randomly assigned to one of two groups. One group will receive the new medicine inavolisib along with ribociclib and fulvestrant. The other group will receive a dummy pill (placebo) instead of inavolisib, plus ribociclib and fulvestrant. You won't know which group you are in.

You would have regular visits to the hospital or clinic for check-ups, blood tests, scans (like CT or MRI scans) to see how the cancer is responding, and to receive your treatment. Fulvestrant is given as an injection, while inavolisib and ribociclib are usually taken as pills. The length of the treatment will vary depending on how you respond and whether you experience any side effects. You will be closely monitored throughout the study. After treatment finishes, there will be follow-up appointments to track your health. The total duration of your participation could be several months or even longer, depending on your individual response to the treatment.