A Study of Abemaciclib (LY2835219) Plus Tamoxifen or Abemaciclib Alone in Women With Metastatic Breast Cancer (Next MONARCH 1)

A Randomized, Open-Label, Phase 2 Study of Abemaciclib Plus Tamoxifen or Abemaciclib Alone, in Women With Previously Treated Hormone Receptor-Positive, HER2-Negative, Metastatic Breast Cancer

The main purpose of this study is to evaluate the safety and efficacy of abemaciclib plus tamoxifen or abemaciclib alone in women with previously treated hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), metastatic breast cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Abemaciclib; Drug: Tamoxifen; Drug: Prophylactic Loperamide

• Study Type: Interventional
• Enrollment (Actual): 234
• Phase: Phase 2

Expanded Access

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

Contacts and Locations

Study Locations

• Argentina
  • Salta, Argentina, 4400
    • Sanatorio Parque
  • Buenos Aires
    • CABA, Buenos Aires, Argentina, C1125ABD
      • CENIT Centro de Neurociencias, Investigacion y Tratamiento
  • Jujuy Province
    • San Salvador de Jujuy, Jujuy Province, Argentina, Y4600APW
      • Fundacion Ars Medica
  • Río Negro Province
    • Viedma, Río Negro Province, Argentina, R8500ACE
      • Clinica Viedma
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, S2000KZE
      • Instituto de Oncología de Rosario
  • Tucumán Province
    • San Miguel de Tucumán, Tucumán Province, Argentina, 4000
      • Centro Para la Atención Integral del Paciente Oncologico (CAIPO)
• Austria
  • Vienna, Austria, 1090
    • AKH
  • Styria
    • Graz, Styria, Austria, 8036
      • Medizinische Universitaet Graz
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Universitatsklinik Innsbruck
• Belgium
  • Charleroi, Belgium, 6000
    • Grand Hopital de Charleroi-Site Notre-Dame
  • Liège, Belgium, 4000
    • Centre Hospitalier Universitaire Sart Tilman
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • Universitair Ziekenhuis Gent
    • Sint-Niklaas, Oost-Vlaanderen, Belgium, 9100
      • Vitaz
• Brazil
  • São Paulo, Brazil, 01317-000
    • Clínica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda
  • São Paulo, Brazil, 01246000
    • Icesp - Instituto Do Câncer Do Estado de São Paulo
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Hospital São Lucas - PUCRS - ONCOLOGY
  • São Paulo
    • Barretos, São Paulo, Brazil, 14784400
      • Fundação Pio XII - Hospital de Câncer de Barretos
• Czechia
  • Prague, Czechia, 100 34
    • Fakultní Nemocnice Královské Vinohrady
  • Prague, Czechia, 150 06
    • Fakultni nemocnice v Motole
  • Prague, Czechia, 128 08
    • Fakultni Poliklinika VFN
  • Praha 4 - Krc, Czechia, 140 59
    • Thomayerova nemocnice
  • Czech Republic
    • Brno, Czech Republic, Czechia, 656 53
      • Masarykuv onkologicky ustav
• France
  • Hauts-de-France
    • Lille, Hauts-de-France, France, 59020
      • Centre Oscar Lambret
  • Provence-Alpes-Côte d'Azur Region
    • Marseille, Provence-Alpes-Côte d'Azur Region, France, 13273
      • Institut Paoli-Calmettes
• Germany
  • Hamburg, Germany, 22087
    • Kath. Marienkrankenhaus gGmbH
  • Baden-Wurttemberg
    • Ulm, Baden-Wurttemberg, Germany, 89081
      • Universitatsklinikum Ulm
• Italy
  • Bologna, Italy, 40139
    • Ospedale Bellaria - Azienda USL di Bologna
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Universitaria Federico II
  • Rome
    • Roma, Rome, Italy, 00161
      • Polic.Umberto I -Univ. La Sapienza
  • Verona
    • Negrar, Verona, Italy, 37024
      • Ospedale Sacro Cuore Don G. Calabria
• Mexico
  • Mexico City, Mexico, 03310
    • Grupo Medico Camino SC
  • Oaxaca City, Mexico, 68000
    • Oaxaca Site Management Organization
  • Sinaloa
    • Culiacán, Sinaloa, Mexico, 80020
      • Neurociencias Estudios Clinicos
  • Toluca
    • San Bernardino, Toluca, Mexico, 50080
      • Centro Hemato Oncologico Privado
• Russia
  • Kazan', Russia, 420029
    • Republic Oncology Dispensary of MoH of Republic Tatarstan
  • Saint Petersburg, Russia, 197758
    • St-Petersburg scientifical practical center of specialized medical care
  • Saint Petersburg, Russia, 198255
    • Saint-Petersburg City Clinical Oncology Dispensary
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Hospital Universitari Vall d'Hebron
  • Madrid, Comunidad de
    • Madrid, Madrid, Comunidad de, Spain, 28034
      • Hospital Universitario Ramon y Cajal
• Taiwan
  • New Taipei City, Taiwan, 235
    • Taipei Medical University Shuang Ho Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 10449
    • Mackay Memorial Hospital
  • Taoyuan, Taiwan, 33305
    • Chang Gung Memorial Hospital - Linkou
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 1250
    • Baskent University Dr. Turgut Noyan Research and Training Center
  • Ankara, Turkey (Türkiye), 06100
    • Hacettepe University Faculty of Medicine
  • Istanbul, Turkey (Türkiye), 34214
    • Medipol Mega University Hospital
  • Istanbul, Turkey (Türkiye), 34668
    • Marmara University Medical Faculty
  • Melikgazi
    • Kayseri, Melikgazi, Turkey (Türkiye), 38039
      • Erciyes University Faculty of Medicine
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • The University of Arizona Cancer Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Dartmouth Hitchcock Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology PLLC
  • Texas
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer and Blood Disorders
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin Clinical Research 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.
• Relapsed or progressed following endocrine therapy.
• Have received prior treatment with at least 2 chemotherapy regimens, of which at least 1 but no more than 2 have been administered in the metastatic setting.
• Have the presence of measureable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
• 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.
• Have adequate organ function.
• Have negative serum pregnancy test within 7 days prior to the first dose of study treatment and agree to use highly effective precautions to prevent pregnancy during the study and for 3 weeks following last dose of study treatment.
• Are able to swallow oral medication.

Exclusion Criteria:

• Have clinical evidence or history of central nervous system metastasis.
• Have a personal history of any of the following conditions: syncope of either unexplained or cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest.
• Have active bacterial or fungal infection (that is, requiring intravenous antibiotics at the time of initiating study treatment) and/or detectable viral infection.
• Have received treatment with a prior cyclin-dependent kinase (CDK4) and CDK 6 inhibitor.
• Have a preexisting chronic condition resulting in persistent diarrhea.
• Have a history of any other cancer (except nonmelanoma skin cancer or carcinoma in-situ of the cervix or breast), unless in complete remission with no therapy for a minimum of 3 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abemaciclib + Tamoxifen; Abemaciclib given orally every 12 hours (Q12H) in combination with tamoxifen given orally every day. Participants may continue to receive treatment until discontinuation criteria are met.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219; Drug: Tamoxifen; Administered orally
Experimental: Abemaciclib; Abemaciclib given orally Q12H. Participants may continue to receive treatment until discontinuation criteria are met.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219
Experimental: Abemaciclib + Prophylactic Loperamide; Abemaciclib given orally Q12H in combination with prophylactic loperamide given orally. Participants may continue to receive treatment until discontinuation criteria are met.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219; Drug: Prophylactic Loperamide; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Progression-free survival time was measured from the date of randomization to the date of investigator-determined objective progression as defined by RECIST v1.1, or death from any cause, whichever occurred first. Progressive disease (PD) is defined as 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. Participants who have neither progressed nor died were censored at the day of their last radiographic tumor assessment (if available) or date of randomization if no post baseline radiographic assessment is available.	Baseline to Objective Disease Progression or Death from Any Cause (Up to 21 Months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR)	Objective response rate was defined as the percentage of participants with CR or PR according to RECIST v1.1. CR was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the LD (longest diameter) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.	Baseline to Objective Disease Progression (Up to 21 Months)
Duration of Response (DoR)	DoR is defined as the time from the date of first evidence of a CR or PR to the date of objective progression or death from any cause, whichever is earlier as defined by Recist v1.1. CR was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR was 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.	Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 21 Months)
Overall Survival (OS)		Baseline to Death from Any Cause (Approximately 36 Months)
Pharmacokinetics (PK): Mean Single Dose Concentration of Abemaciclib and Its Metabolites	Mean single dose concentrations of Abemaciclib and its metabolites (M2 & M20) are reported.	Cycle (C) 1 Day (D) 1 post dose
Pharmacokinetics (PK): Steady State Concentration of Abemaciclib and Its Metabolites	Mean steady state concentrations of Abemaciclib and its metabolites (M2 & M20) are reported. C=Cycle D= Day	Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1 post dose
PK: Mean Single Dose Concentration of Tamoxifen and Endoxifen	Mean single dose concentrations of Tamoxifen and its metabolite (Endoxifen) were reported.	Cycle 1 Day 1 post dose
PK: Multiple Dose Concentration of Tamoxifen and Endoxifen	Mean multiple dose concentrations of Tamoxifen and its metabolite (Endoxifen) were reported.	Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1 post dose
Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)	The EORTC QLQ-C30 self-reported general cancer instrument consists of 30 items covered by 1 of 3 dimensions: Global health status/quality of life (2 items) with scores ranging from 1 (Very Poor) to 7 (Excellent).; Functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), each item scores ranging from 1 (not at all) to 4 (very much); Symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, or financial impact), each item scores ranging from 1 (not at all) to 4 (very much). Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function/QOL or higher levels of symptom burden.	Baseline, 21 Months
Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf)	mBPI-sf is an 11-item instrument used as a multiple-item measure of cancer pain intensity. In addition to pain intensity (4 items), the mBPI-sf is designed for participants to record the presence of pain in general, pain relief, and pain interference with function (general activity, mood, ability to walk, ability to perform normal work, relations with others, sleep, enjoyment of life). Responses for the mBPI-sf items are captured through the use of 11-point numeric rating scales anchored at 0 (no pain or does not interfere) and 10 (pain as bad as you can imagine or completely interferes). The mBPI-sf recall period is 24 hours and typical completion time for this instrument is less than 5 minutes.	Baseline, 21 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

• Hamilton E, Cortes J, Ozyilkan O, Chen SC, Petrakova K, Manikhas A, Jerusalem G, Hegg R, Huober J, Zhang W, Chen Y, Martin M. nextMONARCH Phase 2 randomized clinical trial: overall survival analysis of abemaciclib monotherapy or in combination with tamoxifen in patients with endocrine-refractory HR + , HER2- metastatic breast cancer. Breast Cancer Res Treat. 2022 Aug;195(1):55-64. doi: 10.1007/s10549-022-06662-9. Epub 2022 Jul 12.

Helpful Links

• A Study of Abemaciclib (LY2835219) Plus Tamoxifen or Abemaciclib Alone in Women With Metastatic Breast Cancer (nextMONARCH 1)

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2016
• Primary Completion (Actual): June 15, 2018
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 19, 2016
• First Submitted That Met QC Criteria: April 19, 2016
• First Posted (Estimated): April 21, 2016

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: January 19, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Benzene Derivatives; Stilbenes; Benzylidene Compounds; Tamoxifen; abemaciclib
• Other Study ID Numbers: 16339; I3Y-MC-JPCG (Other Identifier: Eli Lilly and Company); 2016-000288-18 (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 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