Key inclusion criteria for both phases:

1.  Adult females (pre-/peri-/ and post-menopausal), and adult males.
2. A confirmed diagnosis of HR+/ HER2- breast cancer
3. Eligible for fulvestrant therapy and at least one of the following: palbociclib, ribociclib, or abemaciclib, as per local investigator assessment. Previous tolerance to specific CDK4/6 inhibitors and dose levels required.
4. Adequate organ and bone marrow functions.
5. Consent to provide a mandatory FFPE tumor sample.

Key inclusion criteria only for phase III:

1. Previous treatment with an ET (tamoxifen, AI, or oral SERD) as a single agent or in combination, with radiological evidence of breast cancer recurrence or progression while on, or within 12 months of, completing a (neo)adjuvant ET regimen.
2. Provision of mandatory blood samples at screening for central testing using an investigational ctDNA test to be stratified based on PIK3CA/AKT1/PTEN status.
3. Be eligible for fulvestrant and at least one out of palbociclib or ribociclib (depending on the available CDK4/6i options at time of enrolment), as per local investigator assessment.

Key exclusion criteria for both phases:

1. History of another primary malignancy except for malignancy treated with curative intent with no known active disease more than 2 years before the first dose of study intervention and of low potential risk for recurrence.
2. Radiotherapy within 2 weeks prior to study treatment initiation.
3. Major surgery or significant traumatic injury within 4 weeks of the first dose of study treatment.

Key exclusion criteria for the phase III only:

1. Any prior treatment with, AKT, PI3K or mTOR inhibitors.
2. Prior treatment with CDK4/6 inhibitors in the metastatic setting (prior CDK4/6 inhibitors permitted in the adjuvant setting provided there was a CDK4/6i treatment free interval of at least 12 months).
3. More than 1 line of chemotherapy for metastatic disease

Detailed eligibility will be discussed when reaching out to the study team.