Phase 1b Combo w/ Ribociclib and Alpelisib

Open to people ages 18 years and up

• Female or male aged >18 years.
• Willing and able to participate and comply with all study requirements
• Histologically- or cytologically-confirmed advanced or MBC
• HR+/HER2- disease, as determined in the most recently obtained archival tumor tissue sample from a metastatic site, using locally accepted criteria by the local pathology report
• Evaluable disease (measurable and non-measurable): Measurable disease, ie, at least 1 measurable lesion as per RECIST 1.1 (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation).-Subject must have received at least 6 months of a prior continuous endocrine therapy for locally advanced or metastatic breast cancer
• Life expectancy ≥6 months, as judged by the investigator
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Has received no more than 2 prior hormonal regimens for advanced or metastatic disease. Prior hormonal regimens in combination with CDK4/6 inhibitors are allowed.
• Has received no more than 1 prior chemotherapy for locally advanced or metastatic breast cancer.

• Prior or concurrent malignancy whose natural history or treatment may interfere with the safety or efficacy assessment of the investigational regimen
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality
• History of cerebral vascular disease within 6 months prior to the first administration of study drug dose
• History of a pulmonary embolism, or deep venous thrombosis within the last 6 months, or subject has an increased risk of thrombosis as determined by the investigator
• History of pneumonitis or interstitial lung disease
• Leptomeningeal disease or spinal cord compression
• Medical history or ongoing gastrointestinal disorders that could affect absorption of oral therapeutics
• Known human immunodeficiency virus infection
• Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis (eg, hepatitis B or hepatitis C virus), current alcohol abuse, or cirrhosis