Oncology Pipeline

For more than 50 years, Lilly has been dedicated to delivering life-changing medicines and support to people living with cancer and those who care for them. Lilly is determined to build on this heritage and continue making life better for all those affected by cancer around the world. In 2019 Lilly created Loxo Oncology at Lilly, with the goal of rapidly delivering impactful new medicines for people with cancer. Our approach centers on creating new medicines that work in early clinical development and will matter to patients.

Phase 1  

NCT02057133

Breast Cancer

CDK4 & 6 Inhibitor


A Phase 1b Study of Abemaciclib in Combination With Therapies for Patients With Metastatic Breast Cancer*

NCT02057133
Key Inclusion Criteria
  • 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

Key Exclusion Criteria
  • Metastatic breast cancer (MBC) with severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of the disease
  • Brain metastasis without prior radiotherapy
  • Parts A to E, G, and I: Received prior systemic chemotherapy for metastatic disease. However, the participant may have received prior systemic chemotherapy in the neoadjuvant or adjuvant setting
  • Parts A to F, and H: Received prior therapy with a CDK4 & 6 inhibitor; Part G: Received prior therapy with fulvestrant or any PI3K and/or mTOR inhibitor (including LY3023414); Part I: Received prior treatment with abemaciclib in any setting
  • Serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (including interstitial lung disease [ILD], severe dyspnea at rest or requiring oxygen therapy, or history of major surgical resection involving the stomach or small bowel)
  • Central nervous system (CNS) metastasis with either radiotherapy or development of neurological changes ≤14 days prior to receiving study treatment. Participants may be receiving a stable dose of corticosteroids. Screening of asymptomatic participants without history of CNS metastasis is not required. Untreated CNS metastases are not permitted
  • Parts F and H: Cardiac disease including myocardial infarction within 6 months, unstable angina, or New York Heart Association (NYHA) Grade II or greater functional impairment
  • Part G: Type 1 diabetes or a history of gestational diabetes. Participants with type 2 diabetes are eligible if adequate control of blood glucose level is obtained with oral therapy as documented by hemoglobin A1C <7%
  • Part G: Baseline electrocardiogram (obtained from Day -14 to Day -1) with any of the following abnormal findings: ventricular arrhythmia, evidence of acute myocardial ischemia, heart block (of any degree), or QTc prolongation (defined as QTcB ≥450 ms)
*
This clinical trial is being conducted in the United States.
Additional criteria not shown here may exist for individual parts of the study.
Abemaciclib and LY3023414 are administered PO Q12H.
Contact the Lilly Oncology Clinical Trial Navigation Service

Visit www.clinicaltrials.gov for more information on this trial.

The safety and efficacy of the agents under investigation have not been established. There is no guarantee that the agents will receive regulatory approval and become commercially available for the uses being investigated.