A Study of Abemaciclib (LY2835219) in Women With HR+, HER2+ Locally Advanced or Metastatic Breast Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 1 April 2024
• Main ID: NCT02675231
• Date of registration: 03/02/2016
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: A Study of Abemaciclib (LY2835219) in Women With HR+, HER2+ Locally Advanced or Metastatic Breast Cancer monarcHER
• Scientific title: monarcHER: A Phase 2, Randomized, Multicenter, 3-Arm, Open-Label Study to Compare the Efficacy of Abemaciclib Plus Trastuzumab With or Without Fulvestrant to Standard-of-Care Chemotherapy of Physician's Choice Plus Trastuzumab in Women With HR+, HER2+ Locally Advanced or Metastatic Breast Cancer
• Date of first enrolment: May 23, 2016
• Target sample size: 237
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02675231
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, France, Germany, Greece, Italy, Korea, Republic of, Mexico, Spain, United Kingdom, United States

Contacts

• Name: 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)
• Affiliation: Eli Lilly and Company

Key inclusion & exclusion criteria

Inclusion Criteria:

- diagnosis of HR+, HER2+ breast cancer (BC)

- unresectable locally advanced recurrent BC or metastatic BC

- adequate tumor tissue available prior to randomization

- measurable and/or non-measurable disease according to Response Evaluation Criteria in
Solid Tumors (RECIST) version 1.1

- previously received:

- at least 2 HER2-directed therapies for advanced disease

- participant must have received trastuzumab emtansine (T-DM1) in any disease
setting

- must have received a taxane in any disease setting

- may have received any endocrine therapy (excluding fulvestrant)

- have postmenopausal status due to surgical / natural menopause or chemical ovarian
suppression

- performance status (PS) of 0 to 1 on the Eastern Cooperative Oncology Group scale

- left ventricular ejection fraction (LVEF) of 50% or higher at baseline

- adequate organ function

- 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 menopause induced by
gonadotropin-releasing hormone (GnRH) agonist or radiation

- discontinued previous localized radiotherapy for palliative purposes or for lytic
lesions at risk of fracture at least 2 weeks prior to randomization and recovered from
the acute effects of therapy

- discontinued all previous therapies for cancer (including chemotherapy, radiotherapy,
immunotherapy, and endocrine therapy), except trastuzumab, 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

- are able to swallow capsules

Exclusion Criteria:

- have visceral crisis

- known central nervous system (CNS) metastases that are untreated, symptomatic, or
require steroids to control symptoms

- had major surgery within 14 days prior to randomization

- received prior treatment with any cyclin-dependent kinase (CDK) 4 and CDK 6 inhibitor

- received treatment with a drug that has not received regulatory approval for any
indication within 14 or 21 days of randomization for a nonmyelosuppressive or
myelosuppressive agent, respectively

- have serious preexisting medical conditions that, in the judgment of the investigator,
would preclude participation in this study

- history within the last 6 months of symptomatic congestive heart failure, myocardial
infarction, or unstable angina

- history within the last 12 months of any of the following conditions: syncope of
cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden
cardiac arrest

- history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of
the cervix), unless in complete remission with no therapy for a minimum of 3 years

- active bacterial, fungal infection, or detectable viral infection

- have received any recent (within 28 days prior to randomization) live virus
vaccination

- hypersensitivity to trastuzumab, murine proteins, fulvestrant, or to any of the
excipients



Age minimum: 18 Years
Age maximum: N/A
Gender: Female

Health Condition(s) or Problem(s) studied

HER-2 Positive Breast Cancer

Hormone Receptor Positive Breast Cancer

Intervention(s)

Drug: Fulvestrant

Drug: Standard of Care Single Agent Chemotherapy

Drug: Abemaciclib

Drug: Trastuzumab

Primary Outcome(s)

Progression Free Survival (PFS) [Time Frame: Baseline to Progressive Disease or Death from Any Cause (Up To 36 Months)]

Secondary Outcome(s)

Overall Survival (OS) [Time Frame: Baseline to Death from Any Cause (Estimated up to 48 Months)]

Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR) [Time Frame: Baseline to Objective Disease Progression (Up To 36 Months)]

Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) [Time Frame: Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months)]

Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR) [Time Frame: Baseline to Objective Disease Progression (Up To 36 Months)]

Duration of Response (DoR) [Time Frame: Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause (Up To 36 Months)]

Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib and Its Metabolites (M2 and M20) [Time Frame: Cycle(C)1 Day(D)1,C1D15, C2D1, C2D8, C3D1,C3D15, C4D1, C5D1:pre-dose; C1D1, C2D1, C3D1, C4D1, C5D1:post-dose]

Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score [Time Frame: Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months)]

Percentage of Participants With Best Overall Response of CR, PR, or SD With Duration of SD for at Least 6 Months: Clinical Benefit Rate (CBR) [Time Frame: Date of CR, PR or SD to 6 Months Post CR, PR or SD (Up To 36 Months)]

Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) [Time Frame: Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months)]

Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) [Time Frame: Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months)]

Secondary ID(s)

I3Y-MC-JPBZ

15804

2015-003400-24

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 26/05/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02675231