monarcHER: A Phase 2, Randomized, Multicenter, 3-Arm, Open-Label Study to Compare the Efficacy of Abemaciclib Plus Trastuzumab With or Without Fulvestrant to Standard-of-Care Chemotherapy of Physician's Choice Plus Trastuzumab in Women With HR+, HER2+ Locally Advanced or Metastatic Breast Cancer

• diagnosis of HR+, HER2+ breast cancer (BC)

• unresectable locally advanced recurrent BC or metastatic BC

• adequate tumor tissue available prior to randomization

• measurable and/or non-measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

• previously received:

‣ at least 2 HER2-directed therapies for advanced disease

⁃ participant must have received trastuzumab emtansine (T-DM1) in any disease setting

• must have received a taxane in any disease setting

• may have received any endocrine therapy (excluding fulvestrant)

• have postmenopausal status due to surgical / natural menopause or chemical ovarian suppression

• performance status (PS) of 0 to 1 on the Eastern Cooperative Oncology Group scale

• left ventricular ejection fraction (LVEF) of 50% or higher at baseline

• adequate organ function

• negative serum pregnancy test at baseline (within 14 days prior to randomization) and agree to use medically approved precautions to prevent pregnancy during the study and for 12 weeks following the last dose of abemaciclib if menopause induced by gonadotropin-releasing hormone (GnRH) agonist or radiation

• discontinued previous localized radiotherapy for palliative purposes or for lytic lesions at risk of fracture at least 2 weeks prior to randomization and recovered from the acute effects of therapy

• discontinued all previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, and endocrine therapy), except trastuzumab, for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy

• are able to swallow capsules