Abemaciclib (LY2835219) Plus Fulvestrant Compared to Placebo Plus Fulvestrant in Previously Treated Breast Cancer

Study Overview
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Brief Summary
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This study will evaluate the effect of adding abemaciclib to fulvestrant for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer that progressed or recurred after previous treatment with a type of drug known as a CDK4/6 inhibitor and endocrine therapy. Participation could last up to 5 years, depending on how you and your tumor respond.

Official Title
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postMONARCH: A Randomized, Double Blind, Placebo-Controlled, Phase 3 Study to Compare the Efficacy of Abemaciclib Plus Fulvestrant to Placebo Plus Fulvestrant in Participants With HR+, HER2-, Advanced or Metastatic Breast Cancer Following Progression on a CDK4 & 6 Inhibitor and Endocrine Therapy

Conditions
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Breast Neoplasm, Neoplasm Metastasis

Intervention / Treatment
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* Drug: Abemaciclib
* Drug: Fulvestrant
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of HR+, HER2- locally advanced or metastatic breast cancer Have radiologic evidence of disease progression or recurrence either On treatment with a CDK4/6 inhibitor with aromatase inhibitor (AI) as initial therapy for advanced disease, or On/after treatment with a CDK4/6 inhibitor plus endocrine therapy (ET) administered as adjuvant therapy for early stage breast cancer Must be deemed appropriate for treatment with ET If female, have a postmenopausal status by natural or surgical means or by ovarian function suppression Have Response Evaluable Criteria in Solid Tumors (RECIST) evaluable disease (measurable disease and/or nonmeasurable disease) Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale (Oken et al. 1982) Have adequate renal, hematologic, and hepatic organ function Must be able to swallow capsules/tablets Exclusion Criteria: Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis Have symptomatic or untreated central nervous system metastasis Have received any systemic therapy between disease recurrence/progression and study screening Have received more than 1 line of therapy for advanced or metastatic disease. Have received prior chemotherapy for metastatic breast cancer (MBC) Have received prior treatment with fulvestrant, any investigational estrogen receptor (ER)-directed therapy (including selective ER degraders [SERDs] and non-SERDs), any phosphatidylinositol 3-kinase (PI3K)-, mammalian target of rapamycin (mTOR)-, or protein kinase B (AKT)-inhibitor

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: Arm A: Abemaciclib plus Fulvestrant<br>Abemaciclib administered orally in combination with fulvestrant administered intramuscularly (IM). | Drug: Abemaciclib<br>* Administered orally.<br>Drug: Fulvestrant<br>* Administered IM.<br>|
| Active Comparator: Arm B: Placebo plus Fulvestrant<br>Placebo administered orally in combination with fulvestrant administered IM. | Drug: Fulvestrant<br>* Administered IM.<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 |
| --- | --- | --- |
| Progression-Free Survival (PFS) | Investigator assessment | Randomization to the date of first documented progression of disease or death from any cause (estimated as up to 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS | Randomization until death from any cause (estimated as up to 5 years) | 
| PFS | Blinded independent review | Randomization to the date of first documented progression of disease or death from any cause(estimated as up to 3 years) | 
| Objective Response Rate (ORR): Percentage of Participants Who Achieve a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) | ORR | Randomization until measured progressive disease (estimated as up to 1 year) | 
| Clinical Benefit Rate (CBR): Percentage of Participants Who Achieve a Best Overall Response of CR, PR or Stable Disease for Greater than or Equal to (≥) 24 Weeks | CBR | Randomization until measured progressive disease (estimated as up to 1 year) | 
| Disease Control Rate (DCR): Percentage of Participants with a Best Overall Response of CR, PR, and stable disease (SD) | DCR: Percentage of Participants with a Best Overall Response of CR, PR, and SD | Randomization until measured progressive disease (estimated as up to 1 year) | 
| Duration of Response (DoR) | DoR | Date of CR or PR to date of disease progression or death due to any cause (estimated up to 3 years) | 
| Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) Worst Pain Score | The mBPI-sf Worst pain is a single self-reported item that measures the severity of pain based on the worst pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). | Randomization through Follow-up (estimated as up to 3 years) | 
| Time to Deterioration in Physical Function | Physical Function scale includes five items (trouble with strenuous activities; trouble with long walk; trouble with short walk; need to stay in bed or chair; need help with eating, dressing, washing, toilet) in the European Organization for Research and Treatment of Cancer Item Library 19 (EORTC-19). Response options range from 0 (not all) to 4 (very much.) Higher composite scale scores indicate higher function. | Randomization through Follow-up (estimated as up to 3 years) | 
| Pharmacokinetics (PK): Mean Steady State Concentrations of Abemaciclib | PK: Mean Steady State Concentrations of Abemaciclib | Day 1 of Cycle 3 (Cycle = 28 days) |