A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer

NCT ID: NCT02763566

Last Updated: 2026-02-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 463 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-05
• Study Completion Date: 2028-03-31

Brief Summary

The main purpose of this study is to evaluate the efficacy of the study drug abemaciclib in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) locoregionally recurrent or metastatic breast cancer.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)

Abemaciclib given orally every 12 hours (Q12H) plus anastrozole or letrozole given orally every 24 hours (Q24H) on days 1 to 28 of a 28 day cycle. Participants receiving benefit may continue until disease progression.

Group Type: EXPERIMENTAL

Abemaciclib

Intervention Type: DRUG

Administered orally

Anastrozole

Intervention Type: DRUG

Administered orally

Letrozole

Intervention Type: DRUG

Administered orally

Placebo + NSAI

Placebo given orally Q12H plus anastrozole or letrozole given orally Q24H on days 1 to 28 of a 28 day cycle. Participants receiving benefit may continue until disease progression.

Group Type: EXPERIMENTAL

Anastrozole

Intervention Type: DRUG

Administered orally

Letrozole

Intervention Type: DRUG

Administered orally

Placebo

Intervention Type: DRUG

Administered orally

Abemaciclib + Fulvestrant

Abemaciclib given orally Q12H on days 1 to 28 of a 28 day cycle plus fulvestrant intramuscularly (IM) on days 1 and 15 of cycle 1, then on day 1 of cycle 2 and beyond. Participants receiving benefit may continue until disease progression.

Group Type: EXPERIMENTAL

Abemaciclib

Intervention Type: DRUG

Administered orally

Fulvestrant

Intervention Type: DRUG

Administered intramuscularly

Placebo + Fulvestrant

Placebo given orally Q12H on days 1 to 28 of a 28 day cycle plus fulvestrant IM on days 1 and 15 of cycle 1, then on day 1 of cycle 2 and beyond. Participants receiving benefit may continue until disease progression.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Administered orally

Fulvestrant

Intervention Type: DRUG

Administered intramuscularly

Interventions

Abemaciclib

Administered orally

Intervention Type: DRUG

Anastrozole

Administered orally

Intervention Type: DRUG

Letrozole

Administered orally

Intervention Type: DRUG

Placebo

Administered orally

Intervention Type: DRUG

Fulvestrant

Administered intramuscularly

Intervention Type: DRUG

Other Intervention Names

LY2835219

Eligibility Criteria

Inclusion Criteria

• Have a diagnosis of HR+, HER2- breast cancer. Although not required as a protocol procedure, metastatic disease should be considered for biopsy whenever possible to reassess hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status if clinically indicated.

• To fulfill the requirement for HR+ disease, a breast cancer must express, by immunohistochemistry (IHC), at least 1 of the HRs (estrogen receptor [ER], progesterone receptor [PgR]) as defined in the relevant American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
• To fulfill the requirement of HER2- disease, a breast cancer must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression of HER2 by either IHC or in-situ hybridization as defined in the relevant ASCO/CAP guidelines.
• Meet either Inclusion Criterion (2a) or Inclusion Criterion (2b). Participants meeting Inclusion Criterion 2a will be enrolled in Cohort A and participants meeting Inclusion Criterion 2b will be enrolled in Cohort B.
• (2a) Have locoregionally recurrent disease not amenable to resection or radiation therapy with curative intent or metastatic disease.

• Relapsed with radiologic evidence of progression more than 1 year from completion of adjuvant endocrine therapy and have received no prior endocrine therapy for locoregionally recurrent or metastatic disease (Note: prior adjuvant endocrine therapy for localized disease may have included, but is not limited to, anti-estrogens or aromatase inhibitors. In addition, a participant may be enrolled if she has received ≤2 weeks of NSAI in this disease setting immediately preceding screening and agrees to discontinue NSAI until study treatment initiation.) OR
• Presented with de novo metastatic breast cancer (mBC) and not received any prior endocrine therapy. OR
• Relapsed with radiologic evidence of progression less than 1 year from completion of or while receiving adjuvant endocrine therapy (except for letrozole or anastrozole) and have received no prior endocrine therapy for locoregionally recurrent or metastatic disease.
• (2b) Have locoregionally recurrent disease not amenable to resection or radiation therapy with curative intent or metastatic disease.

• Relapsed with radiologic evidence of progression while receiving neoadjuvant or adjuvant endocrine therapy, with no subsequent endocrine therapy received following progression OR
• Relapsed with radiologic evidence of progression within 1 year from completion of adjuvant endocrine therapy, with no subsequent endocrine therapy received following progression OR
• 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 firstline endocrine therapy for metastatic disease. Participants may not have received more than 1 line of endocrine therapy or any prior chemotherapy for metastatic disease OR
• Presented with de novo 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.
• Have postmenopausal status defined as meeting at least 1 of the following:

• Prior bilateral oophorectomy
• Age ≥60 years
• Age <60 years and amenorrheic for at least 12 months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and follicle-stimulating hormone (FSH) and estradiol levels in the postmenopausal range.
• Have 1 of the following, as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1:

• Measurable disease
• Nonmeasurable bone-only disease. Nonmeasurable bone-only disease may include any of the following: blastic bone lesions, lytic bone lesions without a measurable soft tissue component, or mixed lytic-blastic bone lesions without a measurable soft tissue component.
• Have a performance status (PS) of ≤1 on the Eastern Cooperative Oncology (ECOG) scale.
• Have adequate organ function, including:

• Hematologic: absolute neutrophil count (ANC) ≥1.5 × 109/Liter (L), platelets

≥100 × 109/L, and hemoglobin ≥8 g/deciliter (dL). Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator; however, initial study drug treatment must not begin earlier than the day after the erythrocyte transfusion.

• Hepatic: Total bilirubin ≤1.5 times the upper limit of normal (ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST)

≤3.0 times ULN (or ALT and AST ≤5 times ULN if liver metastases are present).

• Renal: serum creatinine ≤1.5 times ULN.
• Have 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 (until the toxicity resolves to either baseline or at least Grade 1) except for residual alopecia or peripheral neuropathy.
• Are able to swallow capsules.
• Are reliable, willing to be available for the duration of the study, and willing to follow study procedures.

Exclusion Criteria

• 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 inflammatory breast cancer.
• Have clinical evidence or a history of central nervous system (CNS) metastasis. Screening test is not required for enrollment.
• Are currently receiving or have previously received chemotherapy for locoregionally recurrent or metastatic breast cancer. (Note: Participants may be enrolled if they received prior [neo]adjuvant chemotherapy for localized disease.)
• Have received prior treatment with everolimus or fulvestrant (for Cohort B only).
• Have received prior treatment with any cyclin-dependent kinases 4 and 6 (CDK4 and CDK6) inhibitor (or participated in any CDK4 and CDK6 inhibitor clinical trial for which treatment assignment is still blinded).
• Have initiated bisphosphonates or approved Receptor activator of nuclear factor kappa-B ligand (RANK-L) targeted agents <7 days prior to randomization.
• Are currently enrolled in a clinical trial involving an investigational product (IP) or non-approved use of a drug or device (other than the IP/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. If a participant is currently enrolled in a clinical trial involving non-approved use of a device, then agreement with the investigator and Eli Lilly and Company (Lilly) clinical research physician (CRP) is required to establish eligibility.
• Have 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 had major surgery within 14 days prior to randomization to allow for post-operative healing of the surgical wound and site(s).
• Have received recent (within 28 days prior to randomization) live attenuated vaccines such as yellow fever vaccine.
• Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (eg, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis).
• 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 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 clinical evidence of active bacterial or fungal infection or active viral infection that, in the judgment of the investigator, would preclude participation in this study (eg, human immunodeficiency virus [HIV] or viral hepatitis). Screening test is not required for enrollment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

ONCOSITE - Centro de Pesquisa Clinica em Oncologia

Ijuí, Rio Grande do Sul, Brazil

Centro Gaucho Integrado De Oncologia, Hematologia, Ensino E Pesquisa

Porto Alegre, Rio Grande do Sul, Brazil

Fundação Pio XII - Hospital de Câncer de Barretos

Barretos, São Paulo, Brazil

Hospital de Base de Sao Jose do Rio Preto

São José do Rio Preto, São Paulo, Brazil

Icesp - Instituto Do Câncer Do Estado de São Paulo

São Paulo, , Brazil

Clínica de Pesquisa e Centro de Estudos em Ginecologia Oncológica e Mamária LTDA

São Paulo, , Brazil

Afflilated Hospital of Bengbu Medical College

Bengbu, Anhui, China

The Fifth Medical Center of PLA General Hospital

Beijing, Beijing Municipality, China

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Fujian Provincial Cancer hospital

Fuzhou, Fujian, China

Fuzhou General hospital of Nanjing Military Command

Fuzhou, Fujian, China

Guangdong Province People's Hospital

Guangzhou, Guangdong, China

Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Guangzhou, Guangdong, China

Guangxi Medical University Affiliated Tumor Hospital

Nanning, Guangxi, China

The Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, China

Harbin Medical University Caner Hospital

Harbin, Heilongjiang, China

Henan Cancer Hospital

Zhengzhou, Henan, China

Wuhan Union Hospital Cancer Center

Wuhan, Hubei, China

Tongji Hospital Tongji Medical, Science & Technology

Wuhan, Hubei, China

Hubei Cancer Hospital

Wuhan, Hubei, China

Hunan Cancer Hospital

Changsha, Hunan, China

Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School

Nanjing, Jiangsu, China

Jiangsu Cancer Hospital

Nanjing, Jiangsu, China

Jiangsu Province Hospital

Nanjing, Jiangsu, China

Jilin Province Tumor Hospital

Changchun, Jilin, China

The 2nd Affiliated Hospital of Dalian Medical University

Dalian, Liaoning, China

Liaoning Cancer Hospital&Institute

Shenyang, Liaoning, China

The first affiliated hospital of China medical university

Shenyang, Liaoning, China

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, China

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Shanghai General Hospital

Shanghai, Shanghai Municipality, China

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, China

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

The Second Affiliate Hospital of Zhejiang University School of medicine

Hangzhou, Zhejiang, China

The Gujarat Cancer & Research Institute (GCRI)

Ahmedabad, Gujarat, India

Healthcare Global Enterprises Limited (HCG)

Bangalore, Karnataka, India

M S Ramaiah Medical College Hospitals

Bangalore, Karnataka, India

Tata Memorial Hospital

Mumbai, Maharashtra, India

Jehangir Hospital

Pune, Maharashtra, India

Dr. B. L. Kapur Memorial Hospital

New Delhi, National Capital Territory of Delhi, India

Christian Medical College Vellore

Ranipet, Tamil Nadu, India

Medica Superspecialty Hospital

Kolkata, West Bengal, India

The Medical Oncology Centre of Rosebank

Johannesburg, Gauteng, South Africa

Eastleigh Breast Care Center

Pretoria, Gauteng, South Africa

Sandton Oncology Centre

Johannesburg, , South Africa

Countries

Brazil; China; India; South Africa

References

Hu X, Zhang Q, Sun T, Yin Y, Li H, Yan M, Tong Z, Li M, Teng Y, Oppermann CP, Kanakasetty GB, Portugal MC, Yang L, Zhang W, Jiang Z. Abemaciclib plus non-steroidal aromatase inhibitor or fulvestrant in women with HR+/HER2- advanced breast cancer: Final results of the randomized phase III MONARCH plus trial. Chin Med J (Engl). 2025 Jun 20;138(12):1477-1486. doi: 10.1097/CM9.0000000000003151. Epub 2024 Oct 10.

Reference Type: DERIVED

PMID: 39385327 (View on PubMed)

Zhang QY, Sun T, Yin YM, Li HP, Yan M, Tong ZS, Oppermann CP, Liu YP, Costa R, Li M, Cheng Y, Ouyang QC, Chen X, Liao N, Wu XH, Wang XJ, Feng JF, Hegg R, Kanakasetty GB, Coccia-Portugal MA, Han RB, Lu Y, Chi HD, Jiang ZF, Hu XC. MONARCH plus: abemaciclib plus endocrine therapy in women with HR+/HER2- advanced breast cancer: the multinational randomized phase III study. Ther Adv Med Oncol. 2020 Oct 22;12:1758835920963925. doi: 10.1177/1758835920963925. eCollection 2020.

Reference Type: DERIVED

PMID: 33149768 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://trials.lillytrialguide.com/en-US/trial/5gZx1MGGogIqeyI6uuKOO

A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer

Other Identifiers

I3Y-CR-JPBQ

Identifier Type: OTHER

Identifier Source: secondary_id

15530

Identifier Type: -

Identifier Source: org_study_id