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

NCT02763566 | Active Not Recruiting Phase 3 Results DMC

• 2 other identifiers: 15530I3Y-CR-JPBQ
• Study Type: interventional
• Target: 463
• Locations: 4 countries
• Sites: 45

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

Keywords

Hormone Receptor-Positive; HER2-Negative; CDK4; CDK6

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) (Abemaciclib + NSAI & Placebo NSAI)

  Progression-free survival time was measured from randomization until the date of objective progression as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1), or death from any cause. 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. Patients 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.

  Randomization to Measured Progressive Disease or Death (up to 26 Months)

Secondary Outcomes (8)

• Progression Free Survival (PFS) (Abemaciclib + Fulvestrant and Placebo + Fulvestrant Arms)

  Randomization to Measured Progressive Disease or Death (up to 26 Months)

• Overall Survival (OS)

  Randomization to Date of Death from Any Cause (Estimated up to 38 Months)

• Percentage of Participants With Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]

  Randomization to Measured Progressive Disease (up to 26 Months)

• Duration of Response (DoR)

  Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 38 Months)

• Percentage of Participants Who Exhibit Stable Disease (SD) or CR or PR [Disease Control Rate (DCR)]

  Randomization to Measured Progressive Disease (up to 26 Months)

Study Arms (4)

Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)

EXPERIMENTAL

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.

Drug: Abemaciclib; Drug: Anastrozole; Drug: Letrozole

Placebo + NSAI

EXPERIMENTAL

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.

Drug: Anastrozole; Drug: Letrozole; Drug: Placebo

Abemaciclib + Fulvestrant

EXPERIMENTAL

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.

Drug: Abemaciclib; Drug: Fulvestrant

Placebo + Fulvestrant

EXPERIMENTAL

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.

Drug: Placebo; Drug: Fulvestrant

Interventions

Anastrozole DRUG

Administered orally

Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI); Placebo + NSAI

Letrozole DRUG

Administered orally

Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI); Placebo + NSAI

Placebo DRUG

Administered orally

Placebo + Fulvestrant; Placebo + NSAI

Fulvestrant DRUG

Administered intramuscularly

Abemaciclib + Fulvestrant; Placebo + Fulvestrant

Abemaciclib DRUG

Administered orally

Also known as: LY2835219

Abemaciclib + Fulvestrant; Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• (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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (45)

ONCOSITE - Centro de Pesquisa Clinica em Oncologia

Ijuí, Rio Grande do Sul, 98700 000, Brazil

Location

Centro Gaucho Integrado De Oncologia, Hematologia, Ensino E Pesquisa

Porto Alegre, Rio Grande do Sul, 90110-270, Brazil

Location

Fundação Pio XII - Hospital de Câncer de Barretos

Barretos, São Paulo, 14784-400, Brazil

Location

Hospital de Base de Sao Jose do Rio Preto

São José do Rio Preto, São Paulo, 15091-000, Brazil

Location

Icesp - Instituto Do Câncer Do Estado de São Paulo

São Paulo, 01246-000, Brazil

Location

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

São Paulo, 01317-000, Brazil

Location

Afflilated Hospital of Bengbu Medical College

Bengbu, Anhui, 233004, China

Location

The Fifth Medical Center of PLA General Hospital

Beijing, Beijing Municipality, 100071, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Fujian Provincial Cancer hospital

Fuzhou, Fujian, 350014, China

Location

Fuzhou General hospital of Nanjing Military Command

Fuzhou, Fujian, 350025, China

Location

Guangdong Province People's Hospital

Guangzhou, Guangdong, 510080, China

Location

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

Guangzhou, Guangdong, 510120, China

Location

Guangxi Medical University Affiliated Tumor Hospital

Nanning, Guangxi, 530021, China

Location

The Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, 50035, China

Location

Harbin Medical University Caner Hospital

Harbin, Heilongjiang, 150081, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

Location

Wuhan Union Hospital Cancer Center

Wuhan, Hubei, 430022, China

Location

Tongji Hospital Tongji Medical, Science & Technology

Wuhan, Hubei, 430030, China

Location

Hubei Cancer Hospital

Wuhan, Hubei, 430079, China

Location

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

Location

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

Nanjing, Jiangsu, 210000, China

Location

Jiangsu Cancer Hospital

Nanjing, Jiangsu, 210009, China

Location

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

Location

Jilin Province Tumor Hospital

Changchun, Jilin, 130012, China

Location

The 2nd Affiliated Hospital of Dalian Medical University

Dalian, Liaoning, 116023, China

Location

Liaoning Cancer Hospital&Institute

Shenyang, Liaoning, 100042, China

Location

The first affiliated hospital of China medical university

Shenyang, Liaoning, 110001, China

Location

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710061, China

Location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

Shanghai General Hospital

Shanghai, Shanghai Municipality, 200080, China

Location

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

The Second Affiliate Hospital of Zhejiang University School of medicine

Hangzhou, Zhejiang, 310052, China

Location

The Gujarat Cancer & Research Institute (GCRI)

Ahmedabad, Gujarat, 380016, India

Location

Healthcare Global Enterprises Limited (HCG)

Bangalore, Karnataka, 560027, India

Location

M S Ramaiah Medical College Hospitals

Bangalore, Karnataka, 560054, India

Location

Tata Memorial Hospital

Mumbai, Maharashtra, 400 012, India

Location

Jehangir Hospital

Pune, Maharashtra, 411001, India

Location

Dr. B. L. Kapur Memorial Hospital

New Delhi, National Capital Territory of Delhi, 110005, India

Location

Christian Medical College Vellore

Ranipet, Tamil Nadu, 632513, India

Location

Medica Superspecialty Hospital

Kolkata, West Bengal, 700099, India

Location

The Medical Oncology Centre of Rosebank

Johannesburg, Gauteng, 2196, South Africa

Location

Eastleigh Breast Care Center

Pretoria, Gauteng, 0081, South Africa

Location

Sandton Oncology Centre

Johannesburg, 2196, South Africa

Location

Related Publications (2)

• 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.

  PMID: 39385327 DERIVED

• 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.

  PMID: 33149768 DERIVED

Related Links

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

MeSH Terms

Conditions

Breast Neoplasms

Interventions

abemaciclib; Anastrozole; Letrozole; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2016
• First Posted: May 5, 2016
• Study Start: December 5, 2016
• Primary Completion: March 29, 2019
• Study Completion (Estimated): March 1, 2028
• Last Updated: February 5, 2026
• Results First Posted: March 30, 2020

Record last verified: 2026-01

Locations

CN (28); ZA (3); BR (6); IN (8)