A Study of Abemaciclib (LY2835219) Plus Hormone Therapy in Participants With Early Breast Cancer (eMonarcHER)

Inclusion Criteria:

• Have confirmed HR+, HER2+ early invasive breast cancer without evidence of disease recurrence or distant metastases
• Have undergone definitive surgery of the primary breast tumor(s)
• Have tumor tissue from breast (preferred) or lymph node
• Have received a minimum of four cycles of chemotherapy in either the neoadjuvant or adjuvant setting per standard of care
• Have completed approximately nine to 20 months of standard HER2-targeted therapy (neoadjuvant/adjuvant combined duration)

• Have received one of the following eligible HER2-targeted adjuvant regimens AND be randomized within 12 weeks of completing the regimen:

  • For participants treated with neoadjuvant therapy and HER2-targeted therapy: A minimum of 4 cycles of T-DM1 in the adjuvant setting. NOTE: Participants may have received up to approximately 6 cycles of adjuvant trastuzumab prior to initiation of T-DM1. Additionally, participants may have switched to trastuzumab-based therapy (monotherapy or in combination with other HER2-targeted therapies) after 4 cycles of T-DM1
  • For participants who had definitive surgery prior to systemic therapy, a minimum of 4 cycles of adjuvant pertuzumab with trastuzumab.

• Have high risk disease, defined by one of the following criteria:

  • Those who received neoadjuvant chemotherapy along with HER2-targeted treatment must have:

    • residual disease in at least one axillary lymph node, or
    • a residual tumor ≥ 5 cm, or
    • a residual tumor of any size that has direct extension to the chest wall and/or skin (ulceration or skin nodules).

  • Those who had definitive surgery prior to systemic therapy and completed adjuvant chemotherapy along with HER2-targeted therapies (trastuzumab and pertuzumab) must have

    • tumor involvement in ≥4 ipsilateral axillary lymph nodes, or
    • tumor involvement in 1 to 3 ipsilateral axillary lymph node(s) and histological Grade 3, or
    • primary invasive tumor size of ≥ 5 cm on pathological evaluation.

Exclusion Criteria:

• Have breast cancer with any of the following features:

  • Disease recurrence or distant metastatic disease (including contralateral axillary lymph nodes)
  • Pathological complete response from any prior early breast cancer treatments. Participants are required to have residual primary tumor and/or lymph node disease at the time of definitive surgery as indicated in inclusion criteria.
  • Inflammatory breast cancer

• Have other medical conditions including:

  • Previous breast cancer (Exceptions: Ipsilateral ductal carcinoma in situ [DCIS] treated by locoregional therapy alone ≥5 years ago; contralateral DCIS treated by locoregional therapy at any time)
  • Other cancer being treated and/or not in complete remission within the last 5 years (Exceptions: Appropriately treated non-melanomatous skin cancer or carcinoma in situ of cervix, bladder, or colon)
  • Females who are pregnant or lactating
  • History of venous thromboembolism
  • Other serious medical conditions

• Have previously received treatment with:

  • Any cyclin-dependent kinase (CDK)4 and CDK6 inhibitor
  • Prior adjuvant treatment with immunotherapy, tucatinib, neratinib, any investigational HER2 directed therapy, or T-DXd (DS8201) for treatment of breast cancer
  • Endocrine therapy (ET) (i.e., tamoxifen, raloxifene or aromatase inhibitor) for breast cancer prevention (without diagnosis of breast cancer)
  • Additional chemotherapy, anti-cancer ET, or HER2-targeted therapy beyond standard of care at study enrollment