A Study of Abemaciclib (LY2835219) In Participants With Previously Treated Breast Cancer That Has Spread (MONARCH 1)

A Phase 2 Study of LY2835219 for Patients With Previously Treated Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer

The main purpose of this study is to evaluate whether the study drug known as abemaciclib is effective in treating participants with breast cancer who have already tried other drug treatments.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Abemaciclib

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Belgium
  • Brussel, Belgium, 1000
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Charleroi, Belgium, 6000
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Leuven, Belgium, 3000
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Liège, Belgium, 4000
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• France
  • Dijon, France, 21034
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Paris, France, 75248
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Spain
  • Barcelona, Spain, 08035
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Madrid, Spain, 28007
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Valencia, Spain, 46015
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• United States
  • Arizona
    • Sedona, Arizona, United States, 86336
      • Northern Arizona Hematology & Oncology Associates
    • Tucson, Arizona, United States, 85715
      • Arizona Clinical Research Center
    • Tucson, Arizona, United States, 85704
      • HOPE Hematology Oncology Physicians and Extenders
  • California
    • San Francisco, California, United States, 94115
      • Univ of California San Francisco
    • Santa Barbara, California, United States, 93105
      • Sansum Medical Research Foundation
  • Colorado
    • Denver, Colorado, United States, 80220
      • Rocky Mountain Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Florida
    • Fort Myers, Florida, United States, 33916
      • Florida Cancer Specialists
    • Miami, Florida, United States, 33176
      • Advanced Medical Specialties
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Maryland Oncology Hematology, P.A.
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology/Hematology PA
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care Inc
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute SCRI
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Oncology Cancer Center
    • Bedford, Texas, United States, 76022
      • Texas Oncology - Bedford
    • Dallas, Texas, United States, 75246
      • Texas Oncology-Baylor Charles A. Sammons Cancer Center
    • Dallas, Texas, United States, 75231
      • Presbyterian Hospital Dallas
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer and Blood Disorders
    • Houston, Texas, United States, 77024
      • Texas Oncology-Memorial City
    • Plano, Texas, United States, 75093
      • Texas Oncology-Plano West
    • Sherman, Texas, United States, 75090-0504
      • Texas Oncology-Sherman
    • The Woodlands, Texas, United States, 77380
      • US Oncology
    • Tyler, Texas, United States, 75702
      • Tyler Cancer Center
  • Washington
    • Vancouver, Washington, United States, 98684
      • Northwest Cancer Specialists PC

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria.

• Have a diagnosis of Hormone Receptor Positive (HR+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) breast cancer.
• Recurrent, locally advanced, unresectable or metastatic breast cancer with disease progression following anti-estrogen therapy.

• Prior treatment with at least 2 chemotherapy regimens:

  • At least 1 of these regimens must have been administered in the metastatic setting.
  • At least 1 of these regimens must have contained a taxane.
  • No more than 2 prior chemotherapy regimens in the metastatic setting.
• Have a performance status (PS) of 0 to 1 on the Eastern Cooperative Oncology Group scale.
• Have discontinued all previous therapies for cancer.
• Have the presence of measureable disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.1.

Exclusion Criteria:

• Have either a history of central nervous system (CNS) metastasis or evidence of CNS metastasis on the magnetic resonance image of brain obtained at baseline.
• Received prior therapy with another cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor.
• Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug.
• Have had major surgery within 14 days of the initial dose of study drug.
• Have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abemaciclib; 200 milligrams (mg) abemaciclib given orally once every 12 hours for 28 days (1 cycle). Participants may continue to receive treatment until discontinuation criteria are met.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With 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.	From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 14 Months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS defined as the time from first dose date 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.	From Date of First Dose until Death Due to Any Cause (Up To 27 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.	From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 14 Months)
Progression Free Survival (PFS)	PFS defined as the time from the first day of therapy to the first evidence of disease progression as defined by 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 first dose, 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 First Dose until Disease Progression or Death Due to Any Cause (Up To 27 Months)
Percentage of Participants With CR, PR or 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.	From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 14 Months)
Percentage of Participants With Tumor Response of Stable Disease (SD) for at Least 6 Months, Partial Response (PR) or Complete Response (CR) (Clinical Benefit Rate)	Clinical benefit rate defined as percentage of patients with best overall response of CR, PR, or SD with a duration of at least 6 months. CR, PR, or SD were defined 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. Percentage of participants = (participants with CR+PR+SD with a duration of at least 6 months /number of participants enrolled) *100.	From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 14 Months)
Number of Participants With Categorical Change From Baseline in Brief Pain Inventory Short Form (mBPI-sf) - Worst Pain Score	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).	Cycle 6 Day 1
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) for Abemaciclib and Metabolites M2 and M20	Area Under the Concentration versus Time Curve from Time Zero to Infinity (AUC[0-∞]) was evaluated for Abemaciclib and Metabolites M2 and M20	Cycle 1 Day 1 pre dose, Cycle 1 Day 15 4 hours (h) and 7 h post dose, Cycle 2 Day 1 pre dose and 3 h post dose, Cycle 3 Day1 pre dose
Number of Participants With Categorical Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Global Health Status Score	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, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms.	Cycle 6 Day 1

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Dickler MN, Tolaney SM, Rugo HS, Cortes J, Dieras V, Patt D, Wildiers H, Hudis CA, O'Shaughnessy J, Zamora E, Yardley DA, Frenzel M, Koustenis A, Baselga J. MONARCH 1, A Phase II Study of Abemaciclib, a CDK4 and CDK6 Inhibitor, as a Single Agent, in Patients with Refractory HR+/HER2- Metastatic Breast Cancer. Clin Cancer Res. 2017 Sep 1;23(17):5218-5224. doi: 10.1158/1078-0432.CCR-17-0754. Epub 2017 May 22. Erratum In: Clin Cancer Res. 2018 Nov 1;24(21):5485.

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2014
• Primary Completion (Actual): April 30, 2016
• Study Completion (Actual): October 22, 2018

Study Registration Dates

• First Submitted: March 31, 2014
• First Submitted That Met QC Criteria: March 31, 2014
• First Posted (Estimate): April 3, 2014

Study Record Updates

• Last Update Posted (Actual): January 21, 2020
• Last Update Submitted That Met QC Criteria: January 10, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Endocrine Therapy, Taxane, MONARCH 1
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 15419; I3Y-MC-JPBN (Other Identifier: Eli Lilly and Company); 2013-005548-27 (Other Identifier: 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