EMBER: A Phase 1a/1b Study of LY3484356 Administered as Monotherapy and in Combination With Anticancer Therapies for Patients With ER+ Locally Advanced or Metastatic Breast Cancer and Other Select Non-Breast Cancers

⁃ 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 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 therapies in any setting.

• Part D: ER+, EEC that has progressed after platinum containing chemotherapy and no prior fulvestrant or aromatase inhibitor therapy.

• Part E: ER+ and HER2+ breast cancer with evidence of locally advanced, unresectable, or metastatic disease.

• Part E: Participants must have received induction taxane chemotherapy combined with trastuzumab + pertuzumab as first-line treatment for advanced/metastatic disease and must not have progressed on this regimen.

• Part E: Participants must not have received more than 1 HER2-directed regimen or any endocrine therapy for advanced disease or any prior CDK4/6 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