A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy

To join this study, you would need to be an adult (18 or older) diagnosed with breast cancer that has spread locally or to other parts of the body, and it cannot be treated with surgery or radiation aimed at curing it. Your cancer must be hormone receptor-positive and HER2-negative, and importantly, it must have a specific gene change called a 'PIK3CA mutation' that has been confirmed by a special test. You should have already received treatment with a CDK4/6 inhibitor alongside hormone therapy, and your cancer should have progressed or returned.

You also need to be generally well enough to take part, meaning you can carry out most daily activities without too much difficulty. Doctors would need to be able to measure your cancer to see if the treatment is working. If you're a woman who could still get pregnant or a man, you would need to be on hormone therapy to reduce female hormones. There are also specific health checks, like blood tests, to make sure your body's organs are working properly.

You wouldn't be able to join if you have a specific type of breast cancer called 'metaplastic breast cancer,' or if you've previously been treated for advanced cancer with certain drugs (called PI3K, AKT, or mTOR inhibitors). Also, if you have type 1 diabetes or type 2 diabetes that needs ongoing medication, or if your cancer came back more than a year after finishing certain early treatments, you might not be eligible.

If you join this study, you will be randomly assigned to receive one of two specific drug combinations (either inavolisib with fulvestrant, or alpelisib with fulvestrant). This means you won't get to choose which combination you receive. You'll have regular hospital visits for various tests, including blood tests, physical exams, and scans (like CT or MRI) to check how the treatment is working and monitor your health. These visits will be more frequent at the beginning of the study and might become less frequent over time. The study treatments will continue for as long as they are helping you and not causing unacceptable side effects. There might also be a specific part of the study where researchers check how the study drugs interact with other common medications like bupropion, omeprazole, and midazolam. The total duration of your participation could vary, as it depends on how well you respond to the treatment, but there will be follow-up appointments even after you stop taking the study drugs.