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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Neoplasm Metastasis; Breast Neoplasm
• Intervention / Treatment: Drug: Abemaciclib; Drug: Fulvestrant; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 368
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or; Phone Number: 1-317-615-4559; Email: ClinicalTrials.gov@lilly.com

Study Locations

• Argentina
  • San Juan, Argentina, 5400
    • CER San Juan
  • Buenos Air
    • Buenos Aires, Buenos Air, Argentina, C1426ABP
      • Fundación Respirar
    • Ciudad Autónoma de Buenos Aire, Buenos Air, Argentina, C1027AAP
      • Centro de Investigaciones Metabólicas (CINME)
  • Ciudad Autónoma De Buenos Aires
    • Caba, Ciudad Autónoma De Buenos Aires, Argentina, 1125
      • Fundación CENIT para la Investigación en Neurociencias
  • Córdoba
    • Río Cuarto, Córdoba, Argentina, 5800
      • Instituto Médico Río Cuarto
  • Tucumán
    • San Miguel de Tucumán, Tucumán, Argentina, 4000
      • Centro Medico San Roque
• Belgium
  • Namur, Belgium, 5000
    • CHU UCL Namur/Site Sainte Elisabeth
  • Antwerpen
    • Brasschaat, Antwerpen, Belgium, 2930
      • Algemeen Ziekenhuis klina
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Fakultni Nemocnice Hradec Kralove
  • Pardubický Kraj
    • Pardubice, Pardubický Kraj, Czechia, 53203
      • Multiscan
• Denmark
  • Hovedstaden
    • Copenhagen, Hovedstaden, Denmark, 2730
      • Herlev and Gentofte Hospital
  • Midtjylland
    • Herning, Midtjylland, Denmark, 7400
      • Regionshospitalet Herning
• France
  • Aquitaine
    • Bordeaux, Aquitaine, France, 33076
      • Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
  • Bretagne
    • Brest, Bretagne, France, 29200
      • Centre Hospitalier Régional Universitaire de Brest - Hôpital Morvan
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44277
      • Hôpital privé du Confluent SAS
  • Vendée
    • La Roche-sur-Yon, Vendée, France, 85000
      • CHD Vendee
• Greece
  • Thessaloniki, Greece, 546 45
    • Euromedica General Clinic of Thessaloniki
  • Achaḯa
    • Patras, Achaḯa, Greece, 26504
      • University Hospital of Patras
  • Attikí
    • Athens, Attikí, Greece, 115 28
      • Alexandra Hospital
  • Irakleío
    • Heraklion, Irakleío, Greece, 711 10
      • University General Hospital of Heraklion
• Hungary
  • Budapest, Hungary, 1122
    • Orszagos Onkologiai Intezet
  • Budapest, Hungary, 1062
    • Magyar Honvédség Egészségügyi Központ
  • Bács-Kiskun
    • Kecskemét, Bács-Kiskun, Hungary, 6000
      • Bacs-Kiskun Varmegyei Oktatokorhaz
  • Győr-Moson-Sopron
    • Gyor, Győr-Moson-Sopron, Hungary, 9024
      • Petz Aladár Egyetemi Oktató Kórház
• Israel
  • HaDarom
    • Be'er Sheva, HaDarom, Israel, 8400000
      • Soroka Medical Center
  • HaMerkaz
    • Petah-Tikva, HaMerkaz, Israel
      • Rabin Medical Center
    • Ramat Gan, HaMerkaz, Israel, 5265601
      • Sheba Medical Center
  • Tell Abīb
    • Tel Aviv, Tell Abīb, Israel, 6423906
      • Sourasky Medical Center
  • Yerushalayim
    • Jerusalem, Yerushalayim, Israel, 9112001
      • Hadassah Medical Center
• Italy
  • Bari, Italy, 70124
    • Instituto Tumori Giovanni Paolo II
  • Grosseto, Italy, 58100
    • Ospedale Misericordia di Grosseto
  • Milano, Italy, 20132
    • Ospedale San Raffaele
  • Viterbo, Italy, 01100
    • ASL Viterbo Ospedale Belcolle
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Friuli-Venezia Giulia
    • Udine, Friuli-Venezia Giulia, Italy, 33100
      • P.O. "S. Maria della Misericordia" Azienda Sanitaria Universitaria Friuli Centrale
• Korea, Republic of
  • Kyǒnggi-do
    • Seongnam, Kyǒnggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
  • Seoul-teukbyeolsi [Seoul]
    • Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 02841
      • Korea University Anam Hospital
  • Taegu-Kwangyǒkshi
    • Daegu, Taegu-Kwangyǒkshi, Korea, Republic of, 41404
      • Kyungpook National University Chilgok Hospital
• Mexico
  • Baja California
    • Mexicali, Baja California, Mexico, 21200
      • Centro de Investigacion en Artritis y Osteoporosis SC
    • Tijuana, Baja California, Mexico, 22010
      • COI Tijuana - Centro Oncológico Internacional
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 45647
      • Centro Oncológico Internacional (COI)
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64060
      • Centro Regiomontano de Investigacion
  • San Luis Potosí
    • San Luis Potosi, San Luis Potosí, Mexico, 78209
      • Oncologico Potosino, S.C.
• Poland
  • Mazowieckie
    • Otwock, Mazowieckie, Poland, 05-400
      • Europejskie Centrum Zdrowia - Oddzial Onkologii
• Spain
  • Badajoz, Spain, 06006
    • Hospital Infanta Cristina
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Maranon
  • Toledo, Spain, 45007
    • Hospital Universitario de Toledo
  • A Coruña [La Coruña]
    • A Coruña, A Coruña [La Coruña], Spain, 15006
      • CHUAC-Hospital Teresa Herrera
  • Balears [Baleares]
    • Palma, Balears [Baleares], Spain, 07120
      • Hospital Universitari Son Espases
  • Catalunya [Cataluña]
    • Barcelona, Catalunya [Cataluña], Spain, 08036
      • Hospital Clinic de Barcelona
  • Murcia, Región De
    • El Palmar, Murcia, Región De, Spain, 30120
      • Hospital Clinico Universitario Virgen de la Arrixaca
  • Málaga
    • Malaga, Málaga, Spain, 29011
      • H.R.U Málaga - Hospital Materno-infantil
  • Navarra
    • Pamplona, Navarra, Spain, 31009
      • Complejo Hospitalario de Navarra
  • Tarragona [Tarragona]
    • Reus, Tarragona [Tarragona], Spain, 43204
      • Hospital Universitari Sant Joan de Reus
  • Valenciana, Comunitat
    • Valencia, Valenciana, Comunitat, Spain, 46017
      • Hospital Universitario Doctor Peset
• Sweden
  • Stockholms
    • Stockholm, Stockholms, Sweden, 171 76
      • Karolinska Universitetssjukhuset Solna
  • Örebro Län [se-18]
    • Örebro, Örebro Län [se-18], Sweden, 701 85
      • Universitetssjukhuset Örebro
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Kaohsiung Medical University Hospital
  • New Taipei City, Taiwan, 231
    • Taipei Tzu Chi General Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation-Linkou Branch
  • Tainan
    • Tainan City, Tainan, Taiwan, 71004
      • Chi Mei Medical Center
• Turkey
  • Adana, Turkey, 01370
    • Adana City Hospital
  • Ankara, Turkey, 06520
    • Memorial Ankara Hastanesi
  • Ankara, Turkey, 06010
    • Gulhane Egitim Arastirma Hastanesi
  • Diyarbakir, Turkey, 21200
    • Dicle Üniversitesi
  • Edirne, Turkey, 22030
    • Trakya University
  • Istanbul, Turkey, 34722
    • TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi
  • Malatya, Turkey, 44280
    • İnönü Üniversitesi Turgut Özal Tıp Merkezi Eğitim ve Araştırma Hastanesi
  • Konya
    • Meram, Konya, Turkey, 42080
      • Necmettin Erbakan Meram Medical Fac.
  • İzmir
    • Karsiyaka, İzmir, Turkey, 009035575
      • Izmir Medical Park Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • St. Joseph's Hospital and Medical Center
  • California
    • Fullerton, California, United States, 92835
      • Providence Medical Foundation
    • Los Alamitos, California, United States, 90720
      • Cancer and Blood Specialty Clinic
    • Los Angeles, California, United States, 90033
      • Keck School of Medicine of USC
    • Los Angeles, California, United States, 90024
      • TRIO-US (Translational Research in Oncology-US)
    • Santa Monica, California, United States, 90404
      • UCLA Hematology/Oncology - Parkside
    • Sylmar, California, United States, 91342
      • Olive View-UCLA Medical Center
    • Torrance, California, United States, 90505
      • Torrance Memorial Physician Network / Cancer Care
    • Whittier, California, United States, 90602
      • PIH Health Hematology Medical Oncology
  • Colorado
    • Denver, Colorado, United States, 80220
      • Rocky Mountain Cancer Center - Hale Parkway
  • Florida
    • Fort Myers, Florida, United States, 33901-8101
      • Florida Cancer Specialists SOUTH/Sarah Cannon Research Institute/SCRI
    • Hollywood, Florida, United States, 33024
      • Millennium Oncology - Hollywood
    • Miami, Florida, United States, 33136
      • University of Miami Hospital and Clinics, Sylvester Cancer Center
    • Pensacola, Florida, United States, 32503
      • Woodlands Medical Specialists, PA
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists SOUTH/Sarah Cannon Research Institute/SCRI
    • West Palm Beach, Florida, United States, 33401
      • Florida Cancer Specialists EAST/Sarah Cannon Research Institute/SCRI
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center
    • Macon, Georgia, United States, 31201
      • Central Georgia Cancer Care
  • Hawaii
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
  • Illinois
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hospital
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Hematology Oncology Clinic- Baton Rouge/Sarah Cannon Research Institute/SCRI
    • Lake Charles, Louisiana, United States, 70601
      • Clinical Trials of SWLA
  • Maine
    • Lewiston, Maine, United States, 04240
      • Central Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Mfsmc-Hjwci
    • Clinton, Maryland, United States, 20735
      • Maryland Oncology Hematology, P.A. - Clinton
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Danvers, Massachusetts, United States, 01923
      • MGH Northshore Cancer Center
    • Fairhaven, Massachusetts, United States, 02719
      • Southcoast Centers for Cancer Care
    • Foxboro, Massachusetts, United States, 02035
      • Dana-Farber Cancer Institute - Foxborough
    • Methuen, Massachusetts, United States, 01844
      • Dana Farber Cancer Center Merrimack Valley
    • Milford, Massachusetts, United States, 01757
      • Dana Farber Cancer Institute
    • Newton, Massachusetts, United States, 02462
      • Mass General Cancer Center
    • South Weymouth, Massachusetts, United States, 02190
      • Dana Farber Cancer Institute
    • Worcester, Massachusetts, United States, 01606
      • Reliant Medical Group
  • Montana
    • Billings, Montana, United States, 59102
      • St. Vincent Frontier Cancer Center
  • New Hampshire
    • Londonderry, New Hampshire, United States, 03053
      • Dana Farber Cancer Center Londonderry
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Comprehensive Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Lifespan Cancer Institute
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Tennessee Oncology-Chattanooga /Sarah Cannon Research Institute/SCRI
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute/SCRI
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology-Nashville/Sarah Cannon Research Institute/SCRI
  • Texas
    • Bedford, Texas, United States, 76022
      • Texas Oncology - Bedford
    • Denton, Texas, United States, 76201
      • Texas Oncology - Denton
    • El Paso, Texas, United States, 79902
      • Texas Oncology, P.A.
    • McKinney, Texas, United States, 75071
      • Texas Oncology - McKinney
    • McKinney, Texas, United States, 75071
      • Woodlands Medical Specialists, PA
    • Mesquite, Texas, United States, 75150
      • Woodlands Medical Specialists, PA
    • Plano, Texas, United States, 75093
      • Texas Oncology-Plano West
    • Plano, Texas, United States, 75075-7787
      • Texas Oncology - Plano East
    • San Antonio, Texas, United States, 78229
      • Mays Cancer Center
    • The Woodlands, Texas, United States, 77380
      • US Oncology
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Tyler Cancer Center
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • Saint George, Utah, United States, 84790
      • Intermountain Healthcare - St. George
  • Vermont
    • Burlington, Vermont, United States, 05401
      • The University of Vermont Medical Center Inc.
  • Virginia
    • Winchester, Virginia, United States, 22601
      • Shenandoah Oncology, P.C.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Abemaciclib plus Fulvestrant; Abemaciclib administered orally in combination with fulvestrant administered intramuscularly (IM).	Drug: Abemaciclib; Administered orally.; Drug: Fulvestrant; Administered IM.
Active Comparator: Arm B: Placebo plus Fulvestrant; Placebo administered orally in combination with fulvestrant administered IM.	Drug: Fulvestrant; Administered IM.; Drug: Placebo; Administered orally.

What is the study measuring?

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
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)
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)
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2022
• Primary Completion (Actual): February 8, 2024
• Study Completion (Estimated): February 16, 2026

Study Registration Dates

• First Submitted: December 22, 2021
• First Submitted That Met QC Criteria: December 22, 2021
• First Posted (Actual): December 27, 2021

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms by Site; Breast Diseases; Neoplastic Processes; Neoplasms; Breast Neoplasms; Neoplasm Metastasis; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant
• Other Study ID Numbers: 18238; I3Y-MC-JPEF (Other Identifier: Eli Lilly and Company); 2021-002301-10 (EudraCT Number); 2023-506771-10-00 (Other Identifier: EU Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No