A Study of LY2835219 (Abemaciclib) in Combination With Therapies for Breast Cancer That Has Spread

NCT ID: NCT02057133

Last Updated: 2026-01-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 198 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-10
• Study Completion Date: 2026-12-31

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.

Conditions

Breast Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LY2835219 + Letrozole

LY2835219 administered orally. Letrozole administered orally. This arm is closed to enrollment.

Group Type: EXPERIMENTAL

LY2835219

Intervention Type: DRUG

Administered orally.

Letrozole

Intervention Type: DRUG

Administered orally.

LY2835219 + Anastrozole

LY2835219 administered orally. Anastrozole administered orally. This arm is closed to enrollment.

Group Type: EXPERIMENTAL

LY2835219

Intervention Type: DRUG

Administered orally.

Anastrozole

Intervention Type: DRUG

Administered orally.

LY2835219 + Tamoxifen

LY2835219 administered orally. Tamoxifen administered orally. This arm is closed to enrollment.

Group Type: EXPERIMENTAL

LY2835219

Intervention Type: DRUG

Administered orally.

Tamoxifen

Intervention Type: DRUG

Administered orally.

LY2835219 + Exemestane

LY2835219 administered orally. Exemestane administered orally. This arm is closed to enrollment.

Group Type: EXPERIMENTAL

LY2835219

Intervention Type: DRUG

Administered orally.

Exemestane

Intervention Type: DRUG

Administered orally.

LY2835219 + Exemestane + Everolimus Dose Escalation

LY2835219 administered orally. Exemestane administered orally. Everolimus administered orally. This arm is closed to enrollment.

Group Type: EXPERIMENTAL

LY2835219

Intervention Type: DRUG

Administered orally.

Exemestane

Intervention Type: DRUG

Administered orally.

Everolimus

Intervention Type: DRUG

Administered orally.

LY2835219 + Exemestane + Everolimus Dose Expansion

LY2835219 administered orally. Exemestane administered orally. Everolimus administered orally. This arm is closed to enrollment.

Group Type: EXPERIMENTAL

LY2835219

Intervention Type: DRUG

Administered orally.

Exemestane

Intervention Type: DRUG

Administered orally.

Everolimus

Intervention Type: DRUG

Administered orally.

LY2835219+ Trastuzumab Dose Escalation

LY2835219 administered orally. Trastuzumab administered intravenously (IV) infusion. This arm is closed to enrollment.

Group Type: EXPERIMENTAL

LY2835219

Intervention Type: DRUG

Administered orally.

Trastuzumab

Intervention Type: DRUG

Administered IV infusion.

LY2835219+ Trastuzumab Dose Expansion

LY2835219 administered orally. Trastuzumab administered IV infusion. This arm is closed to enrollment.

Group Type: EXPERIMENTAL

LY2835219

Intervention Type: DRUG

Administered orally.

Trastuzumab

Intervention Type: DRUG

Administered IV infusion.

LY3023414 + LY2835219 + Fulvestrant Dose Escalation

LY3023414 administered orally. LY2835219 administered orally. Fulvestrant administered intramuscularly (IM).

Group Type: EXPERIMENTAL

LY2835219

Intervention Type: DRUG

Administered orally.

LY3023414

Intervention Type: DRUG

Administered orally.

Fulvestrant

Intervention Type: DRUG

Administered IM.

LY3023414 + LY2835219 + Fulvestrant Dose Expansion

LY3023414 administered orally. LY2835219 administered orally. Fulvestrant administered IM.

Group Type: EXPERIMENTAL

LY2835219

Intervention Type: DRUG

Administered orally.

LY3023414

Intervention Type: DRUG

Administered orally.

Fulvestrant

Intervention Type: DRUG

Administered IM.

LY2835219 +Trastuzumab +Pertuzumab +Loperamide Dose Escalation

LY2835219 administered orally. Loperamide administered orally. Trastuzumab administered IV infusion. Pertuzumab administered IV infusion.

Group Type: EXPERIMENTAL

LY2835219

Intervention Type: DRUG

Administered orally.

Trastuzumab

Intervention Type: DRUG

Administered IV infusion.

Pertuzumab

Intervention Type: DRUG

Administered IV infusion.

Loperamide

Intervention Type: DRUG

Administered orally.

LY2835219 +Trastuzumab + Pertuzumab +Loperamide Dose Expansion

Hormone 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.

Group Type: EXPERIMENTAL

LY2835219

Intervention Type: DRUG

Administered orally.

Trastuzumab

Intervention Type: DRUG

Administered IV infusion.

Pertuzumab

Intervention Type: DRUG

Administered IV infusion.

Loperamide

Intervention Type: DRUG

Administered orally.

Endocrine therapy

Intervention Type: DRUG

Endocrine therapy administered orally.

LY2835219 + Endocrine Therapy

LY2835219 administered orally. Ongoing endocrine therapy administered orally.

Group Type: EXPERIMENTAL

LY2835219

Intervention Type: DRUG

Administered orally.

Endocrine therapy

Intervention Type: DRUG

Endocrine therapy administered orally.

Interventions

LY2835219

Administered orally.

Intervention Type: DRUG

Letrozole

Administered orally.

Intervention Type: DRUG

Anastrozole

Administered orally.

Intervention Type: DRUG

Tamoxifen

Administered orally.

Intervention Type: DRUG

Exemestane

Administered orally.

Intervention Type: DRUG

Everolimus

Administered orally.

Intervention Type: DRUG

Trastuzumab

Administered IV infusion.

Intervention Type: DRUG

LY3023414

Administered orally.

Intervention Type: DRUG

Fulvestrant

Administered IM.

Intervention Type: DRUG

Pertuzumab

Administered IV infusion.

Intervention Type: DRUG

Loperamide

Administered orally.

Intervention Type: DRUG

Endocrine therapy

Endocrine therapy administered orally.

Intervention Type: DRUG

Other Intervention Names

Abemaciclib

Eligibility Criteria

Inclusion Criteria

• 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.
• Have adequate organ function, including:

• Hematologic: Absolute neutrophil count (ANC) ≥1.5 x 10^9/liter (L), platelets ≥ 100 x 10^9/L, and hemoglobin ≥ 8 gram/deciliter (g/dL).
• Hepatic: Bilirubin ≤1.5 times upper limits of normal (ULN), alanine aminotransferase (ALT) ≤ 3.0 times ULN.
• Renal: Serum creatinine ≤ 1.5 times ULN.
• Have a performance status of ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale.
• Have 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 Part F and H: concurrent treatment with trastuzumab emtansine (T-DM1) is not allowed.

Exclusion Criteria

• 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

Highlands Oncology Group - Duplicate 2

Rogers, Arkansas, United States

University of California - San Diego

La Jolla, California, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Columbia University College of Phys & Surgeons

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Providence Cancer Center Oncology Hematology Care

Portland, Oregon, United States

Univ of Pittsburgh Cancer Inst. (UPCI)

Pittsburgh, Pennsylvania, United States

Peggy and Charles Stephenson Oklahoma Cancer Center

Nashville, Tennessee, United States

Tennessee Oncology PLLC

Nashville, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 35223458 (View on PubMed)

Gelbert 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.

Reference Type: DERIVED

PMID: 24919854 (View on PubMed)

Related Links

https://www.lillytrialguide.com/en-US/studies/breast-cancer/JPBH#?postal=

Click here for more information about this study: A Study of Abemaciclib (LY2835219) in Combination With Other Therapies in Participants With Breast Cancer That Has Spread

Other Identifiers

I3Y-MC-JPBH

Identifier Type: OTHER

Identifier Source: secondary_id

15252

Identifier Type: -

Identifier Source: org_study_id