A Study of Abemaciclib (LY2835219) Combined With Fulvestrant in Women With Hormone Receptor Positive HER2 Negative Breast Cancer (MONARCH 2)

MONARCH 2: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Fulvestrant With or Without Abemaciclib, a CDK4/6 Inhibitor, for Women With Hormone Receptor Positive, HER2 Negative Locally Advanced or Metastatic Breast Cancer

The main purpose of this study is to compare progression-free survival for women with hormone receptor positive (HR+), human epidermal growth factor receptor (HER2) negative advanced breast cancer receiving either abemaciclib + fulvestrant or fulvestrant alone. Participants will be randomized to abemaciclib or placebo in a 2:1 ratio. The study will last about 9 months for each participant.

For the endocrine naïve cohort, all participants will received abemaciclib + fulvestrant.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 669
• Phase: Phase 3

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Icon Cancer Centre South Brisbane
    • Southport, Queensland, Australia, 4215
      • Gold Coast University Hospital
  • South Australia
    • Kurralta Park, South Australia, Australia, 5037
      • Ashford Cancer Centre Research
  • Victoria
    • East Bentleigh, Victoria, Australia, 3165
      • Monash Cancer Centre
  • Western Australia
    • Subiaco, Western Australia, Australia, 6008
      • St. John of God Subiaco Hospital
• Belgium
  • Liège, Belgium, 4000
    • Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Antwerp University Hospital
  • Bruxelles-Capitale, Région de
    • Brussels, Bruxelles-Capitale, Région de, Belgium, 1090
      • UZ Brussel
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • UZ Leuven
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Center
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Regional Cancer Program
    • Toronto, Ontario, Canada, M3M 0B2
      • Humber River Hospital
    • Toronto, Ontario, Canada, M5B 1W8
      • Unity Health Toronto, St. Michael's Hospital
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Universitets Hospital
  • Roskilde, Denmark, 4000
    • Roskilde Sygehus
  • Capital Region
    • Copenhagen, Capital Region, Denmark, 2730
      • Herlev and Gentofte Hospital
• Finland
  • Turku, Finland, 20520
    • Turun yliopistollinen keskussairaala
  • Pirkanmaa
    • Tampere, Pirkanmaa, Finland, 33520
      • Tampereen yliopistollinen sairaala
  • Uusimaa
    • Helsinki, Uusimaa, Finland, 00029
      • Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus)
• France
  • La Chaussée-Saint-Victor, France, 41260
    • Polyclinique de Blois
  • Le Mans, France, 72000
    • Clinique Victor Hugo - Centre Jean Bernard
  • Doubs
    • Besançon, Doubs, France, 25000
      • CHU Besançon
  • Puy-de-Dôme
    • Clermont-Ferrand, Puy-de-Dôme, France, 63011
      • Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne
• Germany
  • Hamburg, Germany, 20249
    • Facharztzentrum Eppendorf
  • Baden-Wurttemberg
    • Ludwigsburg, Baden-Wurttemberg, Germany, 71640
      • Klinikum Ludwigsburg
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Universitaetsklinikum Tuebingen
  • Bavaria
    • Augsburg, Bavaria, Germany, 86150
      • Gemeinschaftspraxis hop-augsburg
    • München, Bavaria, Germany, 80336
      • Klinikum der Ludwig-Maximilians-Universitaet Muenchen
• Greece
  • Chania, Greece, 73300
    • Chania General Hospital 'Agios Georgios'
  • Achaḯa
    • Pátrai, Achaḯa, Greece, 26504
      • University Hospital of Patras
  • Attikí
    • Athens, Attikí, Greece, 11522
      • Agios Savvas Regional Cancer Hospital
  • Krítí
    • Heraklion, Krítí, Greece, 71110
      • University General Hospital of Heraklion
• Italy
  • Bologna, Italy, 40139
    • Ospedale Bellaria - Azienda USL di Bologna
  • Padua, Italy, 35128
    • Istituto Oncologico Veneto IRCCS
  • Emilia-Romagna
    • Cona, Emilia-Romagna, Italy, 44124
      • Azienda Ospedaliero Universitaria S.Anna
  • Roma
    • Rome, Roma, Italy, 00144
      • Istituto Nazionale Tumori Regina Elena
• Japan
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center
  • Kagoshima, Japan, 892-0833
    • Sagara Hospital
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute
  • Osaka, Japan, 540-0006
    • National Hospital Organization Osaka Medical Center
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 464-8681
      • Aichi Cancer Center Hospital
  • Chiba
    • Chiba, Chiba, Japan, 260-8717
      • Chiba Cancer Center
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Ehime
    • Matsuyama, Ehime, Japan, 791-0280
      • National Hospital Organization Shikoku Cancer Center
  • Fukuoka
    • Kurume, Fukuoka, Japan, 830-0013
      • Kurume General Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0804
      • National Hospital Organization Hokkaido Cancer Center
  • Hyōgo
    • Nishinomiya, Hyōgo, Japan, 663-8501
      • Hyogo College of Medicine
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 216-8511
      • St. Marianna University School of Medicine Hospital
  • Niigata
    • Niigata, Niigata, Japan, 951-8566
      • Niigata Cancer Center Hospital
  • Saitama
    • Ina-machi, Saitama, Japan, 362-0806
      • Saitama Prefectural Cancer Center
  • Tochigi
    • Shimotsuke, Tochigi, Japan, 329- 0498
      • Jichi Medical University Hospital
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8677
      • Tokyo Met Cancer & Infectious Diseases Center Komagome Hp
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
    • Koto, Tokyo, Japan, 135-8550
      • Japanese Foundation for Cancer Research
• Mexico
  • Estado de Baja California
    • Tijuana, Estado de Baja California, Mexico, 22010
      • Hospital Angeles
  • Guanajuato
    • León, Guanajuato, Mexico, 37178
      • Preparaciones Oncológicas S.C.
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 45647
      • Centro Oncológico Internacional (COI)
  • Mexico City
    • Mexico City, Mexico City, Mexico, 03310
      • Grupo Medico Camino Sc
    • Mexico City, Mexico City, Mexico, 14070
      • Instituto Nacional de Cancerologia
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64000
      • OCA Hospital
    • Monterrey, Nuevo León, Mexico, 64710
      • Tecnologico de Monterrey
• Poland
  • Bialystok, Poland, 15-027
    • Bialostockie Centrum Onkologii, Oddzial Onkologii Klinicznej
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-214
      • Uniwersyteckie Centrum Kliniczne
  • Łódź Voivodeship
    • Lodz, Łódź Voivodeship, Poland
      • Centrum Terapii Wspolczesnej J. M. Jasnorzewska Spolka Komandytowo-Akcyjna
• Puerto Rico
  • PR
    • Bayamón, PR, Puerto Rico, 00959
      • Puerto Rico Hematology/Oncology Group
• Romania
  • Bucharest, Romania, 010976
    • Ianuli Med Consult SRL
  • Cluj
    • Cluj-Napoca, Cluj, Romania, 400058
      • S.C. Medisprof SRL
  • Dolj
    • Craiova, Dolj, Romania, 200347
      • Centrul de Oncologie "Sfântul Nectarie"
• Russia
  • Arkhangelskaya oblast
    • Arkhangelsk, Arkhangelskaya oblast, Russia, 163045
      • Arkhangelsk Clinical Oncological Dispensary
  • Ivanovo Oblast
    • Ivanovo, Ivanovo Oblast, Russia, 153040
      • Regional Budgetary Healthcare Institution 'Ivanovo Regional Oncology Dispensary'
  • Moscow
    • Moscow, Moscow, Russia, 115478
      • Fed State Budgetary Inst "N.N. Blokhin Med Center of Oncology" MHRF
  • Russian Federation
    • Kursk, Russian Federation, Russia, 305035
      • Kursk Regional Oncology Dispensary
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russia, 197758
      • N.N.Petrov Research Institute of Oncology
    • Saint Petersburg, Sankt-Peterburg, Russia, 198255
      • Saint-Petersburg City Clinical Oncology Dispensary
• South Korea
  • Chungcheongbuk-do [Chungbuk]
    • Cheongju-si, Chungcheongbuk-do [Chungbuk], South Korea, 28644
      • Chungbuk National University Hospital
  • Incheon-gwangyeoksi [Incheon]
    • Incheon, Incheon-gwangyeoksi [Incheon], South Korea, 22332
      • Inha University Hospital
    • Namdong-gu, Incheon-gwangyeoksi [Incheon], South Korea, 21565
      • Gachon University Gil Medical Center
  • Kyǒnggi-do
    • Seongnam, Kyǒnggi-do, South Korea, 13620
      • Seoul National University Bundang Hospital
  • Seoul-teukbyeolsi [Seoul]
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 3080
      • Seoul National University Hospital
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 3722
      • Severance Hospital, Yonsei University Health System
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 5505
      • Asan Medical Center
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 6351
      • Samsung Medical Center
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 6591
      • The Catholic Univ. of Korea Seoul St. Mary's Hospital
  • Ulsan-Kwangyǒkshi
    • Ulsan, Ulsan-Kwangyǒkshi, South Korea, 44033
      • Ulsan University Hospital
• Spain
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Alicante
    • Elche, Alicante, Spain, 03202
      • Hospital General Universitario de Elche
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Hospital Universitari Vall d'Hebron
  • Lleida [Lérida]
    • Lleida, Lleida [Lérida], Spain, 25198
      • Hospital Universitario Arnau de Vilanova de Lleida
  • Madrid, Comunidad de
    • Madrid, Madrid, Comunidad de, Spain, 28041
      • Hospital Universitario 12 de octubre
  • Murcia, Región de
    • Murcia, Murcia, Región de, Spain, 30008
      • Hospital General Universitario Morales Meseguer
  • València
    • Valencia, València, Spain, 46010
      • Hospital Quironsalud Valencia
• Switzerland
  • Geneva, Switzerland, 1211
    • HUG-Hôpitaux Universitaires de Genève
  • Canton of Basel-City
    • Basel, Canton of Basel-City, Switzerland, 4031
      • Universitätsspital Basel
  • Canton of Bern
    • Thun, Canton of Bern, Switzerland, 3600
      • Spital Thun
• Taiwan
  • Kaohsiung City, Taiwan, 81362
    • Kaohsiung Veterans General Hospital
  • Kaohsiung City, Taiwan, 80756
    • Kaohsiung Medical University Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taoyuan District, Taiwan, 333
    • Chang Gung Medical Foundation-Linkou Branch
  • Kaohsiung
    • Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan, 83301
      • Chang Gung Memorial Hospital at Kaohsiung
• United States
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • St. Bernards Medical Center
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology Group
  • California
    • La Jolla, California, United States, 92037-0845
      • University of California - San Diego
    • Riverside, California, United States, 92505
      • Kaiser Permanente
    • San Francisco, California, United States, 94115
      • Univ of California San Francisco
    • Stanford, California, United States, 94305
      • Stanford University Clinic
  • Florida
    • Atlantis, Florida, United States, 33462
      • Palm Beach Cancer Institue
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists - South
    • Palm Beach Gardens, Florida, United States, 33410
      • Palm Beach Cancer Institue
    • St. Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists - North
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center, Richard M. Shulze Family Foundation Outpatient Center
    • Wellington, Florida, United States, 33414
      • Palm Beach Cancer Institue
    • West Palm Beach, Florida, United States, 33401
      • Palm Beach Cancer Institue
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer & Blood Center, LLC
    • Rome, Georgia, United States, 30165
      • Harbin Clinic
  • Illinois
    • Quincy, Illinois, United States, 62301
      • Quincy Medical Group
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • Pharmasite Research, Inc.
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Lansing, Michigan, United States, 48910
      • Breslin Cancer Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology/Hematology PA
  • Missouri
    • City of Saint Peters, Missouri, United States, 63376
      • Washington University Medical School
    • Creve Coeur, Missouri, United States, 63141
      • Washington University Medical School
    • Joplin, Missouri, United States, 64804
      • Freeman Cancer Institute
    • Kansas City, Missouri, United States, 64111
      • St Lukes Hospital
    • St Louis, Missouri, United States, 63110
      • Washington University Medical School
    • St Louis, Missouri, United States, 63129
      • Washington University Medical School
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-0001
      • Dartmouth-Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10029
      • ICAHN School of Medicine at Mount Sinai
    • Rochester, New York, United States, 14621
      • Rochester General Hospital
    • Rochester, New York, United States, 14625
      • Rochester General Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Novant Health, Oncology Research Institute
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74146
      • Oklahoma Cancer Specialists & Research Institute, LLC
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Research/USD
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • The Boston Baskin Cancer Group
    • Nashville, Tennessee, United States, 37203
      • SMO Sarah Cannon Research Inst.
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • Oncology Consultants P.A.
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists
  • Washington
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Walla Walla, Washington, United States, 99362
      • St Mary Regional Cancer Center

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- breast cancer

• Have locally advanced disease not amenable to curative treatment by surgery or metastatic disease. In addition, participants must fulfill 1 of the following criteria:

  • relapsed with radiologic evidence of progression while receiving neoadjuvant or adjuvant endocrine therapy, with no subsequent endocrine therapy received following progression
  • relapsed with radiologic evidence of progression within 1 year from completion of adjuvant endocrine therapy, with no subsequent endocrine therapy received following progression
  • relapsed with radiologic evidence of progression more than 1 year from completion of adjuvant endocrine therapy and then subsequently relapsed with radiologic evidence of progression after receiving treatment with either an antiestrogen or an aromatase inhibitor as first-line endocrine therapy for metastatic disease. Participants may not have received more than 1 line of endocrine therapy or any prior chemotherapy for metastatic disease
  • presented de novo with metastatic disease and then relapsed with radiologic evidence of progression after receiving treatment with either an antiestrogen or an aromatase inhibitor as first line endocrine therapy for metastatic disease. Participants may not have received more than 1 line of endocrine therapy or any prior chemotherapy for metastatic disease
  • for the endocrine naïve cohort: Must not have received prior endocrine therapy in current or prior disease setting
• Have postmenopausal status due to either surgical/natural menopause or ovarian suppression (initiated at least 28 days prior to Day 1 of Cycle 1) with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin
• Have a negative serum pregnancy test at baseline (within 14 days prior to randomization) and agree to use medically approved precautions to prevent pregnancy during the study and for 12 weeks following the last dose of abemaciclib if postmenopausal status is due to ovarian suppression with a GnRH agonist
• Have either measurable disease or nonmeasurable bone only disease
• Have a performance status ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale
• Have discontinued previous therapies for cancer (including specifically, aromatase inhibitors, anti-estrogens, chemotherapy, radiotherapy, and immunotherapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (until the toxicity resolves to either baseline or at least Grade 1) except for residual alopecia or peripheral neuropathy

Exclusion Criteria

• Are currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study
• Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis visceral crisis is not the mere presence of visceral metastases but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of the disease
• Have clinical evidence or history of central nervous system metastasis
• Have received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, everolimus, or any CDK4/6 inhibitor. For the endocrine naïve cohort: In addition, have received treatment with any prior endocrine therapy
• Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days prior to randomization of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively
• Have received recent (within 28 days prior to randomization) yellow fever vaccination
• Have had major surgery within 14 days prior to randomization of study drug to allow for post-operative healing of the surgical wound and site(s)
• Have a personal history within the last 12 months of any of the following conditions: syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest
• Have inflammatory breast cancer or a history of any other cancer (except nonmelanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years
• Have received an autologous or allogeneic stem-cell transplant
• Have active bacterial or fungal infection, or detectable viral infection
• Have initiated bisphosphonates or approved Receptor activator of nuclear factor kappa-B (RANK) ligand targeted agents <7 days prior to randomization

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: Abemaciclib + Fulvestrant; Abemaciclib 150 milligram (mg) administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.	Drug: Abemaciclib; Administered Orally; Other Names: LY2835219; Drug: Fulvestrant; Administered IM
Placebo Comparator: Placebo + Fulvestrant; Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.	Drug: Placebo; Administered Orally; Drug: Fulvestrant; Administered IM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.	From Date of Randomization until Disease Progression or Death Due to Any Cause (Up To 31 Months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.	From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months)
Duration of Response (DOR)	DOR was the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR were defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.	From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 31 Months)
Percentage of Participants Achieving CR, PR or Stable Disease (SD) (Disease Control Rate [DCR])	Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.	From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months)
Percentage of Participants With CR, PR or SD With a Duration of At Least 6 Months (Clinical Benefit Rate [CBR])	Clinical benefit rate defined as percentage of participants with best overall response of CR, PR, or SD with a duration of at least 6 months.CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions.PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. Percentage of participants=(participants with CR+PR+SD with a duration of at least 6 months /number of participants enrolled) *100.PD was at least a 20% increase in sum of the diameters of target lesions,with reference being the smallest sum on study and an absolute increase of at least 5 mm or unequivocal progression of non-target lesions,or 1 or more new lesions.	From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months)
Change From Baseline in Pain and Symptom Burden Assessment Using the Modified Brief Pain Inventory-Short Form (mBPI-sf)	A self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). The overall change is based on the estimated main treatment effect. Least square (LS) Mean value was controlled for Treatment, visit, Treatment*Visit and baseline.	Baseline, End of Study (Up To 31 Months)
Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of Abemaciclib, Its Metabolites M2 and M20	Area Under the Plasma Concentration versus Time Curve from Time Zero to Infinity (AUC[0-∞]) was evaluated for Abemaciclib and Metabolites M2 and M20.	Cycle 1 Day 1 2-4 hours (h) post dose, Cycle 1 Day 15 4 and 7h post dose, Cycle 2 Day 1 pre dose and 3h post dose, Cycle 3 Day1 pre dose
Change From Baseline in Health Status Using the EuroQol 5-Dimension 5 Level (EQ-5D 5L)	European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. The EQ-5D-5L is assessed using a visual analog scale (VAS) that ranged from 0 to 100mm, where 0 is the worst health you can imagine and 100 is the best health you can imagine. A higher score indicates better health state. LS Mean value was controlled for Treatment, visit, Treatment*Visit and baseline.	Baseline, End of Study (Up To 31 Months)
Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)	EORTC QLQ-C30 v3.0 was 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, scores range from 0 to 110 with higher scores representing a better level of functioning. For symptoms scales, scores range from 0 to 100 with higher scores representing a greater degree of symptoms. LS Mean value of changing from baseline to short follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment*Visit and baseline.	Baseline, Short Term Follow Up (Up To 31 Months)
Change From Baseline to Short Term Follow up in Quality of Life Using the EORTC QLQ-BR23 (Breast) Questionnaire	EORTC-QLQ-BR23 measured multi-item functional scales for body image, sexual functioning and future perspective and measured single item symptoms scales which assessed systemic therapy side effects, breast symptoms and arm symptoms. For functional scales, scores ranged from 0 to 100 where higher scores represented a better level of functioning. For symptoms scales, scores ranged from 0 to 100 where higher scores represented a greater degree of symptoms. LS Mean value of changing from baseline to short follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment*Visit and baseline.	Baseline, Short Term Follow Up (Up To 31 Months)
Overall Survival (OS)	OS defined as the time from the date of randomization to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive. The final analysis of the OS outcome was conducted after 440 OS events had been observed.	From Date of Randomization until Death Due to Any Cause (Up To 72 Months)

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

General Publications

• Goetz MP, Okera M, Wildiers H, Campone M, Grischke EM, Manso L, Andre VAM, Chouaki N, San Antonio B, Toi M, Sledge GW Jr. Safety and efficacy of abemaciclib plus endocrine therapy in older patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: an age-specific subgroup analysis of MONARCH 2 and 3 trials. Breast Cancer Res Treat. 2021 Apr;186(2):417-428. doi: 10.1007/s10549-020-06029-y. Epub 2021 Jan 3.
• Neven P, Rugo HS, Tolaney SM, Iwata H, Toi M, Goetz MP, Kaufman PA, Lu Y, Haddad N, Hurt KC, Sledge GW Jr. Abemaciclib plus fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in premenopausal women: subgroup analysis from the MONARCH 2 trial. Breast Cancer Res. 2021 Aug 23;23(1):87. doi: 10.1186/s13058-021-01463-2.
• Inoue K, Masuda N, Iwata H, Takahashi M, Ito Y, Miyoshi Y, Nakayama T, Mukai H, van der Walt JS, Mori J, Sakaguchi S, Kawaguchi T, Tanizawa Y, Llombart-Cussac A, Sledge GW Jr, Toi M. Japanese subpopulation analysis of MONARCH 2: phase 3 study of abemaciclib plus fulvestrant for treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer that progressed on endocrine therapy. Breast Cancer. 2021 Sep;28(5):1038-1050. doi: 10.1007/s12282-021-01239-8. Epub 2021 Apr 1.
• Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Conte P, Lu Y, Barriga S, Hurt K, Frenzel M, Johnston S, Llombart-Cussac A. The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor-Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy-MONARCH 2: A Randomized Clinical Trial. JAMA Oncol. 2020 Jan 1;6(1):116-124. doi: 10.1001/jamaoncol.2019.4782.
• Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Frenzel M, Lin Y, Barriga S, Smith IC, Bourayou N, Llombart-Cussac A. MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. J Clin Oncol. 2017 Sep 1;35(25):2875-2884. doi: 10.1200/JCO.2017.73.7585. Epub 2017 Jun 3.

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2014
• Primary Completion (Actual): February 14, 2017
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: April 4, 2014
• First Submitted That Met QC Criteria: April 4, 2014
• First Posted (Estimated): April 8, 2014

Study Record Updates

• Last Update Posted (Estimated): October 21, 2025
• Last Update Submitted That Met QC Criteria: October 17, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: MONARCH 2
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Fulvestrant; abemaciclib
• Other Study ID Numbers: 15362; I3Y-MC-JPBL (Other Identifier: Eli Lilly and Company); 2013-004728-13 (EudraCT 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