Parts A to E, G, and I: Hormone-receptor-positive (HR+), HER2-negative metastatic breast cancer (MBC)
Parts F and H: HER2-positive MBC
Part A (LY2835219 + letrozole): Except for ongoing therapy with letrozole, must not have received prior systemic endocrine therapy for metastatic disease
Part B (LY2835219 + anastrozole): Except for ongoing therapy with anastrozole, must not have received prior systemic endocrine therapy for metastatic disease
Part C (LY2835219 + tamoxifen): May have received prior systemic endocrine therapy for metastatic disease and may be receiving ongoing therapy with tamoxifen
Part D (LY2835219 + exemestane): Must have received prior systemic endocrine therapy with at least one nonsteroidal aromatase inhibitor (anastrozole, letrozole) for metastatic disease and may be receiving ongoing therapy with exemestane
Part E (LY2835219 + exemestane + everolimus): Must have received prior systemic endocrine therapy with at least one nonsteroidal aromatase inhibitor (anastrozole, letrozole) for metastatic disease and may be receiving ongoing therapy with either exemestane or exemestane + everolimus
Part F (LY2835219 + trastuzumab): Must have received at least one chemotherapy regimen for metastatic disease and may be receiving ongoing therapy with trastuzumab. Must have an estimated left ventricular ejection fraction within the normal range by either echocardiogram or multigated acquisition (MUGA) scan
Part G (abemaciclib + LY3023414 + fulvestrant): May have received prior systemic endocrine therapy with at least one nonsteroidal aromatase inhibitor (anastrozole, letrozole) for metastatic disease
Part H (abemaciclib + trastuzumab + pertuzumab): Must have received at least one chemotherapy regimen for metastatic disease. May be receiving ongoing therapy with trastuzumab and/or pertuzumab at the time of study entry. Must have an estimated left ventricular ejection fraction (LVEF) within the normal range by either echocardiogram or multigated acquisition (MUGA) scan
Part I (abemaciclib + endocrine therapy): Must have demonstrated evidence of disease progression on a cyclin-dependent kinase (CDK) 4 & 6 inhibitor (either palbociclib or ribociclib) plus endocrine therapy for advanced or metastatic disease as the most recent therapy immediately preceding study entry. Should remain on the current endocrine therapy while receiving abemaciclib
Parts A to F: Measurable disease or nonmeasurable but evaluable bone disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Parts G to I: Measurable disease as defined by RECIST 1.1
All parts except F and H: Postmenopausal status or premenopausal status if continuing or beginning ovarian suppression with a luteinizing hormone-releasing hormone (LHRH) agonist such as goserelin
Parts H and I: Must be able and willing to undergo mandatory tumor biopsies prior to study treatment and at the time of discontinuation from study treatment
Have adequate organ function, including:
- Hematologic: Absolute neutrophil count (ANC) ≥1.5 x 10⁹/L, platelets ≥100 x 10⁹/L, and hemoglobin ≥8 g/dL
- Hepatic: Bilirubin ≤1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT) ≤3.0 x ULN
- Renal: Serum creatinine ≤1.5 x ULN
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Discontinued all previous therapies for breast cancer (including chemotherapy, radiotherapy, immunotherapy, and investigational therapy), except for ongoing corresponding combination therapy, for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug(s), 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. For parts F and H, concurrent treatment with trastuzumab emtansine (T-DM1) is not allowed

Oncology Pipeline

gynecologic cancer