A Study of LY2835219 (Abemaciclib) in Combination With Therapies for Breast Cancer That Has Spread
A Phase 1b Study of Abemaciclib in Combination With Therapies for Patients With Metastatic Breast Cancer
2 other identifiers
interventional
198
1 country
13
Brief Summary
This study evaluates the safety of abemaciclib in combination therapies (letrozole, anastrozole, tamoxifen, exemestane, exemestane plus everolimus, trastuzumab, LY3023414 plus fulvestrant, pertuzumab plus trastuzumab with loperamide, or ongoing endocrine therapy) for breast cancer that has spread to other parts of the body.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2014
Longer than P75 for phase_1
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 4, 2014
CompletedFirst Posted
Study publicly available on registry
February 6, 2014
CompletedStudy Start
First participant enrolled
March 10, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 15, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2026
ExpectedJanuary 26, 2026
January 1, 2026
7 years
February 4, 2014
January 23, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants with One or More Drug-Related Adverse Events
Number of participants with one or more drug-related adverse events
Baseline through study completion (estimated as 12 months)
Secondary Outcomes (5)
Pharmacokinetics: Maximum Concentration (Cmax) of LY2835219, Letrozole, Anastrozole, Tamoxifen, Exemestane, Everolimus, Trastuzumab, LY3023414, Fulvestrant, and Pertuzumab
Cycle 1 up to Cycle 5 (21 or 28 Day Cycle): Predose and at multiple timepoints, depending on study part.
Number of Participants with a Complete or Partial Tumor Response (Overall Response Rate)
Baseline to study completion (estimated as 12 months)
Progression Free Survival (PFS)
First dose to progressive disease or death of any cause (estimated as 12 months)
Change in MD Anderson Symptom Inventory (MDASI) Score from Baseline
Baseline, through study completion (estimated as 12 months)
Pharmacokinetics: Area under the Curve (AUC) of LY2835219, Letrozole, Anastrozole, Tamoxifen, Exemestane, Everolimus, Trastuzumab, LY3023414, Fulvestrant, and Pertuzumab
Cycle 1 up to Cycle 5 (21 or 28 Day Cycle): Predose and at multiple timepoints, depending on study part.
Study Arms (13)
LY2835219 + Letrozole
EXPERIMENTALLY2835219 administered orally. Letrozole administered orally. This arm is closed to enrollment.
LY2835219 + Anastrozole
EXPERIMENTALLY2835219 administered orally. Anastrozole administered orally. This arm is closed to enrollment.
LY2835219 + Tamoxifen
EXPERIMENTALLY2835219 administered orally. Tamoxifen administered orally. This arm is closed to enrollment.
LY2835219 + Exemestane
EXPERIMENTALLY2835219 administered orally. Exemestane administered orally. This arm is closed to enrollment.
LY2835219 + Exemestane + Everolimus Dose Escalation
EXPERIMENTALLY2835219 administered orally. Exemestane administered orally. Everolimus administered orally. This arm is closed to enrollment.
LY2835219 + Exemestane + Everolimus Dose Expansion
EXPERIMENTALLY2835219 administered orally. Exemestane administered orally. Everolimus administered orally. This arm is closed to enrollment.
LY2835219+ Trastuzumab Dose Escalation
EXPERIMENTALLY2835219 administered orally. Trastuzumab administered intravenously (IV) infusion. This arm is closed to enrollment.
LY2835219+ Trastuzumab Dose Expansion
EXPERIMENTALLY2835219 administered orally. Trastuzumab administered IV infusion. This arm is closed to enrollment.
LY3023414 + LY2835219 + Fulvestrant Dose Escalation
EXPERIMENTALLY3023414 administered orally. LY2835219 administered orally. Fulvestrant administered intramuscularly (IM).
LY3023414 + LY2835219 + Fulvestrant Dose Expansion
EXPERIMENTALLY3023414 administered orally. LY2835219 administered orally. Fulvestrant administered IM.
LY2835219 +Trastuzumab +Pertuzumab +Loperamide Dose Escalation
EXPERIMENTALLY2835219 administered orally. Loperamide administered orally. Trastuzumab administered IV infusion. Pertuzumab administered IV infusion.
LY2835219 +Trastuzumab + Pertuzumab +Loperamide Dose Expansion
EXPERIMENTALHormone Receptor Negative (HR-): LY2835219 administered orally. Loperamide administered orally. Trastuzumab administered IV infusion. Pertuzumab administered IV infusion. Hormone Receptor Positive (HR+): LY2835219 administered orally. Loperamide administered orally. Trastuzumab administered IV infusion. Pertuzumab administered IV infusion. Endocrine therapy administered orally.
LY2835219 + Endocrine Therapy
EXPERIMENTALLY2835219 administered orally. Ongoing endocrine therapy administered orally.
Interventions
Administered orally.
Administered orally.
Administered orally.
Administered IV infusion.
Administered orally.
Administered IM.
Administered IV infusion.
Administered orally.
Endocrine therapy administered orally.
Eligibility Criteria
You may qualify if:
- Have a diagnosis of hormone receptor positive (HR+), human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer for Parts A to E, G, and I.
- Have a diagnosis of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer for Parts F and H.
- For Part A (LY2835219 + letrozole): Except for ongoing therapy with letrozole, the participant must not have received prior systemic endocrine therapy for metastatic disease.
- For Part B (LY2835219 + anastrozole): Except for ongoing therapy with anastrozole, the participant must not have received prior systemic endocrine therapy for metastatic disease.
- For Part C (LY2835219 + tamoxifen): The participant may have received prior systemic endocrine therapy for metastatic disease and may be receiving ongoing therapy with tamoxifen.
- For Part D (LY2835219 + exemestane): The participant 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.
- For Part E (LY2835219 + exemestane + everolimus): The participant 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.
- For Part F (LY2835219 + trastuzumab):The participant must have received at least 1 chemotherapy regimen for metastatic disease and may be receiving ongoing therapy with trastuzumab. The participant must have an estimated left ventricular ejection fraction within the normal range by either echocardiogram or multigated acquisition (MUGA) scan
- For Part G (abemaciclib + LY3023414 + fulvestrant): The participant may have received prior systemic endocrine therapy with at least one nonsteroidal aromatase inhibitor (anastrozole, letrozole) for metastatic disease.
- For Part H: (abemaciclib + trastuzumab + pertuzumab): The participant must have received at least 1 chemotherapy regimen for metastatic disease. The participant may be receiving ongoing therapy with trastuzumab and/or pertuzumab at the time of study entry. The participant must have an estimated left ventricular ejection fraction (LVEF) within the normal range by either echocardiogram or multigated acquisition (MUGA) scan.
- For Part I (abemaciclib + endocrine therapy): The participant must have demonstrated evidence of disease progression on a Cyclin Dependent Kinase 4 (CDK4) and Cyclin Dependent Kinase 6 (CDK6) inhibitor (either palbociclib or ribociclib) plus endocrine therapy for advanced or metastatic disease as the most recent therapy immediately preceding study entry. The participant should remain on the current endocrine therapy while receiving abemaciclib.
- For Parts A, B, C, D, E, and F: Have either measureable disease or nonmeasureable but evaluable bone disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
- For Part G, H, and I: Have measureable disease as defined by RECIST 1.1.
- For all Parts except Part F and H: Participants must have either post-menopausal status or pre-menopausal 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.
- +6 more criteria
You may not qualify if:
- Have metastatic breast cancer with severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of the disease.
- Have brain metastasis without prior radiotherapy.
- For Parts A, B, C, D, E, G and I: Have received prior systemic chemotherapy for metastatic disease. However, the participant may have received prior systemic chemotherapy in the neoadjuvant or adjuvant setting.
- For Parts A, B, C, D, E, F, H: Have received prior therapy with a CDK4/6 inhibitor, Part G: Have received prior therapy with fulvestrant or any PI3K and/or mTOR inhibitor (including LY3023414); Part I: Have received prior treatment with abemaciclib in any setting.
- Have 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).
- Have 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.
- For 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.
- For Part G: Have type 1 diabetes mellitus or a history of gestational diabetes mellitus. Participants with a type 2 diabetes mellitus are eligible if adequate control of blood glucose level is obtained with oral therapy as documented by Hemoglobin A1c \<7%.
- For Part G: Have a 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 milliseconds).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (13)
Highlands Oncology Group - Duplicate 2
Rogers, Arkansas, 72758, United States
University of California - San Diego
La Jolla, California, 92037-0845, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Mayo Clinic
Rochester, Minnesota, 55905-0002, United States
Columbia University College of Phys & Surgeons
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27514, United States
Providence Cancer Center Oncology Hematology Care
Portland, Oregon, 97213, United States
Univ of Pittsburgh Cancer Inst. (UPCI)
Pittsburgh, Pennsylvania, 15213, United States
Peggy and Charles Stephenson Oklahoma Cancer Center
Nashville, Tennessee, 37203, United States
Tennessee Oncology PLLC
Nashville, Tennessee, 37203, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232-6307, United States
South Texas Accelerated Research Therapeutics (START)
San Antonio, Texas, 78229-3307, United States
Related Publications (2)
Tolaney SM, Beeram M, Beck JT, Conlin A, Dees EC, Puhalla SL, Rexer BN, Burris HA, Jhaveri K, Helsten T, Becerra C, Kalinsky K, Moore KN, Manuel AM, Lithio A, Price GL, Chapman SC, Litchfield LM, Goetz MP. Abemaciclib in Combination With Endocrine Therapy for Patients With Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: A Phase 1b Study. Front Oncol. 2022 Feb 10;11:810023. doi: 10.3389/fonc.2021.810023. eCollection 2021.
PMID: 35223458DERIVEDGelbert LM, Cai S, Lin X, Sanchez-Martinez C, Del Prado M, Lallena MJ, Torres R, Ajamie RT, Wishart GN, Flack RS, Neubauer BL, Young J, Chan EM, Iversen P, Cronier D, Kreklau E, de Dios A. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Invest New Drugs. 2014 Oct;32(5):825-37. doi: 10.1007/s10637-014-0120-7. Epub 2014 Jun 13.
PMID: 24919854DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
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 Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
February 4, 2014
First Posted
February 6, 2014
Study Start
March 10, 2014
Primary Completion
March 15, 2021
Study Completion (Estimated)
December 1, 2026
Last Updated
January 26, 2026
Record last verified: 2026-01