Inclusion Criteria:

All Study Parts

• Participants must be willing to provide adequate archival tissue sample.
• Participants must be willing to use highly effective birth control.
• Participants must have adequate organ function.
• Participants must be able to swallow capsules.

Dose escalation - participants must have one of the following:

• Parts A and B: ER+ HER2- breast cancer with evidence of locally advanced unresectable or metastatic disease who have had the following:
  • Part A: may have had up to 1 prior regimen of any kind for in the advanced/metastatic setting and no prior cyclin-dependent kinase 4/6 (CDK4/6) inhibitor therapy;
  • Part B: may have had up to 2 prior regimens, no more than 1 of which may be endocrine therapy in the advanced/metastatic setting, and must have received a prior CDK4/6 inhibitor.
• Cohort E4: No prior everolimus.
• Cohort E5: No prior alpelisib and must have a known and activating phosphatidylinositol 3-kinase catalytic α (PIK3Cα) mutation as determined by local testing.
• Part C: ER+, human epidermal growth factor receptor 2 positive (HER2+) breast cancer with evidence of locally advanced unresectable or metastatic disease who have had at least 2 HER2-directed regimens in any setting.
• Part D: ER+, EEC that has progressed after platinum containing chemotherapy and no prior fulvestrant or aromatase inhibitor therapy.
• Participants with ER+/HER2- breast cancer enrolled in this study must have had evidence of clinical benefit while on endocrine therapy for at least 24 months in the adjuvant setting or at least 6 months in the advanced/metastatic setting or have untreated de novo metastatic breast cancer.

Exclusion Criteria:

• Participants must not have certain infections such as hepatitis or tuberculosis or HIV that are not well controlled.
• Participants must not have another serious medical condition.
• Participants must not have cancer of the central nervous system that is unstable.
• Participants must not be pregnant or breastfeeding.

Eligibility last updated 11/15/21. Questions regarding updates should be directed to the study team contact.