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

Study Overview
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Brief Summary
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The main purpose of this study is to measure how well abemaciclib works in participants with early breast cancer who are taking hormone therapy after surgery. Participants must have breast cancer that is hormone receptor positive (HR+) and human epidermal receptor 2 positive (HER2+). Your participation could last up to 10 years depending on how you and your tumor respond.

Official Title
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eMonarcHER: A Randomized, Double Blind, Placebo-Controlled Phase 3 Study of Abemaciclib Plus Standard Adjuvant Endocrine Therapy in Participants With High-Risk, Node-Positive, HR+, HER2+ Early Breast Cancer Who Have Completed Adjuvant HER2-Targeted Therapy

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Drug: Abemaciclib
* Drug: Standard Adjuvant ET
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abemaciclib Plus (+) Endocrine Therapy (ET)<br>Abemaciclib administered orally and standard adjuvant ET (physician's choice) administered according to package label. | Drug: Abemaciclib<br>* Administered orally.<br>* Other names: LY2835219;Drug: Standard Adjuvant ET<br>* Administered according to label instructions.<br>|
| Active Comparator: Placebo + ET<br>Placebo administered orally and standard adjuvant ET (physician's choice) administered according to package label. | Drug: Standard Adjuvant ET<br>* Administered according to label instructions.<br>Drug: Placebo<br>* Administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive Disease Free Survival (IDFS) | IDFS as defined by the STEEP System | Randomization to Recurrence or Death from Any Cause (up to 10 Years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS | Randomization to Death from Any Cause (up to 10 Years) | 
| Distant Relapse-Free Survival (DRFS) | DRFS | Randomization to Distant Recurrence or Death from Any Cause (up to 10 Years) | 
| Percentage of Participants with Central Nervous System (CNS) Metastases as First Site of Disease Recurrence | Percentage of Participants with CNS Metastases as First Site of Disease Recurrence | Randomization to Distant Recurrence or Death from Any Cause (up to 10 Years) | 
| Change from Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scale Score | EORTC QLQ-C30 is a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, cognitive, emotional, and social), global health status, and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms. | Cycle 1 up to end of Year 4 | 
| Change from Baseline in the EuroQOL 5 Dimension 5 Level (EQ-5D 5L) Index Score | The EQ-5D is a self-administered questionnaire that participants complete to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a scale from 1 to 5 (no problem, slight problems, moderate problems, severe problems, and extreme problems/unable to, respectively). These combinations of attributes were converted into a weighted Health State Index score; the possible values for the Health State Index score range from less than 0 (0 equals health state of dead; severe problems in all 5 dimensions) to 1.0 (full health; no problem in any dimension). Higher score indicates better health state. | Cycle 1 up to end of Year 4 | 
| Pharmacokinetics (PK): Mean Steady State Concentrations of Abemaciclib | PK: Mean Steady State Concentrations of Abemaciclib | Day 1 of Cycles 1-3 (Cycle = 28 days) |