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

Inclusion Criteria:

• Have a diagnosis of HR+, HER2- breast cancer. Although not required as a protocolprocedure, metastatic disease should be considered for biopsy whenever possible toreassess 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, byimmunohistochemistry (IHC), at least 1 of the HRs (estrogen receptor [ER],progesterone receptor [PgR]) as defined in the relevant American Society ofClinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.

• To fulfill the requirement of HER2- disease, a breast cancer must notdemonstrate, at initial diagnosis or upon subsequent biopsy, overexpression ofHER2 by either IHC or in-situ hybridization as defined in the relevant ASCO/CAPguidelines.

• Meet either Inclusion Criterion (2a) or Inclusion Criterion (2b). Participantsmeeting Inclusion Criterion 2a will be enrolled in Cohort A and participants meetingInclusion Criterion 2b will be enrolled in Cohort B.

• (2a) Have locoregionally recurrent disease not amenable to resection or radiationtherapy with curative intent or metastatic disease.

• Relapsed with radiologic evidence of progression more than 1 year fromcompletion of adjuvant endocrine therapy and have received no prior endocrinetherapy for locoregionally recurrent or metastatic disease (Note: prioradjuvant endocrine therapy for localized disease may have included, but is notlimited to, anti-estrogens or aromatase inhibitors. In addition, a participantmay be enrolled if she has received ≤2 weeks of NSAI in this disease settingimmediately preceding screening and agrees to discontinue NSAI until studytreatment initiation.) OR

• Presented with de novo metastatic breast cancer (mBC) and not received anyprior endocrine therapy. OR

• Relapsed with radiologic evidence of progression less than 1 year from completion ofor while receiving adjuvant endocrine therapy (except for letrozole or anastrozole)and have received no prior endocrine therapy for locoregionally recurrent ormetastatic disease.

• (2b) Have locoregionally recurrent disease not amenable to resection or radiationtherapy with curative intent or metastatic disease.

• Relapsed with radiologic evidence of progression while receiving neoadjuvant oradjuvant endocrine therapy, with no subsequent endocrine therapy receivedfollowing progression OR

• Relapsed with radiologic evidence of progression within 1 year from completionof adjuvant endocrine therapy, with no subsequent endocrine therapy receivedfollowing progression OR

• Relapsed with radiologic evidence of progression more than 1 year fromcompletion of adjuvant endocrine therapy and then subsequently relapsed withradiologic evidence of progression after receiving treatment with either anantiestrogen or an aromatase inhibitor as firstline endocrine therapy formetastatic disease. Participants may not have received more than 1 line ofendocrine therapy or any prior chemotherapy for metastatic disease OR

• Presented with de novo metastatic disease and then relapsed with radiologicevidence of progression after receiving treatment with either an antiestrogenor an aromatase inhibitor as first-line endocrine therapy for metastaticdisease. Participants may not have received more than 1 line of endocrinetherapy 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 ofchemotherapy, tamoxifen, toremifene, or ovarian suppression) andfollicle-stimulating hormone (FSH) and estradiol levels in the postmenopausalrange.

• Have 1 of the following, as defined by the Response Evaluation Criteria in SolidTumors (RECIST) v1.1:

• Measurable disease

• Nonmeasurable bone-only disease. Nonmeasurable bone-only disease may includeany of the following: blastic bone lesions, lytic bone lesions without ameasurable soft tissue component, or mixed lytic-blastic bone lesions without ameasurable 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 receiveerythrocyte transfusions to achieve this hemoglobin level at the discretion ofthe investigator; however, initial study drug treatment must not begin earlierthan the day after the erythrocyte transfusion.

• Hepatic: Total bilirubin ≤1.5 times the upper limit of normal (ULN) and alanineaminotransferase (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 forlytic lesions at risk of fracture at least 2 weeks prior to randomization andrecovered from the acute effects of therapy (until the toxicity resolves to eitherbaseline 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 tofollow study procedures.

Exclusion Criteria:

• Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis.Visceral crisis is not the mere presence of visceral metastases, but implies severeorgan dysfunction as assessed by symptoms and signs, laboratory studies, and rapidprogression 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 locoregionallyrecurrent or metastatic breast cancer. (Note: Participants may be enrolled if theyreceived 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 andCDK6) inhibitor (or participated in any CDK4 and CDK6 inhibitor clinical trial forwhich treatment assignment is still blinded).

• Have initiated bisphosphonates or approved Receptor activator of nuclear factorkappa-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 thisstudy), or concurrently enrolled in any other type of medical research judged not tobe scientifically or medically compatible with this study. If a participant iscurrently enrolled in a clinical trial involving non-approved use of a device, thenagreement with the investigator and Eli Lilly and Company (Lilly) clinical researchphysician (CRP) is required to establish eligibility.

• Have received treatment with a drug that has not received regulatory approval forany indication within 14 or 21 days of randomization for a nonmyelosuppressive ormyelosuppressive agent, respectively.

• Have had major surgery within 14 days prior to randomization to allow forpost-operative healing of the surgical wound and site(s).

• Have received recent (within 28 days prior to randomization) live attenuatedvaccines such as yellow fever vaccine.

• Have serious preexisting medical conditions that, in the judgment of theinvestigator, would preclude participation in this study (eg, history of majorsurgical resection involving the stomach or small bowel, or preexisting Crohn'sdisease or ulcerative colitis).

• Have a personal history within the last 12 months of any of the followingconditions: syncope of cardiovascular etiology, ventricular tachycardia, ventricularfibrillation, or sudden cardiac arrest.

• Have a history of any other cancer (except nonmelanoma skin cancer or carcinomain-situ of the cervix), unless in complete remission with no therapy for a minimumof 3 years.

• Have received an autologous or allogeneic stem-cell transplant.

• Have clinical evidence of active bacterial or fungal infection or active viralinfection that, in the judgment of the investigator, would preclude participation inthis study (eg, human immunodeficiency virus [HIV] or viral hepatitis). Screeningtest is not required for enrollment.