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

INTERVENTION: Trade Name: Verzenios Product Name: Abemaciclib Product Code: LY2835219 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: LY2835219 Other descriptive name: Abemaciclib Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use Trade Name: Faslodex Product Name: Fulvestrant Pharmaceutical Form: Solution for injection INN or Proposed INN: Fulvestrant Other descriptive name: Fulvestrant Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 250‐ Trade Name: Fulvestrant Mylan Product Name: Fulvestrant Product Code: L02BA03 Pharmaceutical Form: Solution for injection INN or Proposed INN: Fulvestrant Other descriptive name: Fulvestrant Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 250‐ CONDITION: HR+, HER2‐, Advanced or Metastatic Breast Cancer ; MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864 Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: To compare the efficacy of fulvestrant with or without abemaciclib Primary end point(s): To compare PFS of fulvestrant with or without abemaciclib as determined by investigator assessment using RECIST 1.1 Secondary Objective: To further compare the efficacy of fulvestrant with or without abemaciclib; To further characterize the safety profile of abemaciclib in combination with fulvestrant; To compare PRO measures of fulvestrant with or without abemaciclib; To characterize the pharmacokinetics (PK) of abemaciclib in combination with fulvestrant Timepoint(s) of evaluation of this end point: first occurrence of documented disease progression per RECIST 1.1, or death from any cause in the absence of documented progressive disease. SECONDARY OUTCOME: Secondary end point(s): Efficacy endpoints: overall survival (OS), progression‐free survival (PFS) by BICR, objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), duration of response (DoR); Safety endpoint: including but not limited to TEAEs, SAEs, deaths and clinical laboratory abnormalities; Time to worsening in worst pain via the mBPISF worst pain item; Time to deterioration in physical function via the EORTC IL‐19; Concentrations of abemaciclib Timepoint(s) of evaluation of this end point: first occurrence of documented disease progression per RECIST 1.1, or death from any cause in the absence of documented progressive disease.; At the end of the trial INCLUSION CRITERIA: ‐Have a diagnosis of HR+, HER2‐ breast cancer ‐Have either advanced disease not amenable to curative surgical treatment or metastatic disease. ‐Have radiologic evidence of disease progression or recurrence either On treatment with a CDK4 & 6 inhibitor (palbociclib, ribociclib, or abemaciclib) plus AI as initial therapy for advanced disease, or plus ET administered as adjuvant therapy for early‐stage breast cancer ‐Have either measurable disease or non‐measurable but evaluable disease. ‐Have a performance status (PS) of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale (Oken et al. 1982). ‐Must be deemed appropriate for treatment with ET. ‐Have discontinued previous treatments and recovered from the acute effects of therapy to at least Grade 1, except for residual alopecia and peripheral neuropathy. ‐Have adequate organ function. ‐Males and females may participate. Male participants must agree to use hormone suppression with a