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Breast NeoplasmsPhase 1NCT02057133

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

A Phase 1 study testing LY2835219, Letrozole and Anastrozole in people with Breast Neoplasms, run by Eli Lilly and Company at 13 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Neoplasms
What is being tested?
LY2835219, Letrozole and Anastrozole
Could I receive a placebo?
No, everyone receives an active treatment
How many people
198 participants
Where
13 sitesUnited States
Study dates
10 Mar 2014to Dec 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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).

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27514

  • University of California - San Diego

    La Jolla, California, 92037-0845

  • Peggy and Charles Stephenson Oklahoma Cancer Center

    Nashville, Tennessee, 37203

  • Tennessee Oncology PLLC

    Nashville, Tennessee, 37203

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232-6307

  • Columbia University College of Phys & Surgeons

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Univ of Pittsburgh Cancer Inst. (UPCI)

    Pittsburgh, Pennsylvania, 15213

  • Providence Cancer Center Oncology Hematology Care

    Portland, Oregon, 97213

  • Mayo Clinic

    Rochester, Minnesota, 55905-0002

  • Highlands Oncology Group - Duplicate 2

    Rogers, Arkansas, 72758

  • South Texas Accelerated Research Therapeutics (START)

    San Antonio, Texas, 78229-3307

Other trials in United States

About this study

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

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.

Being tested
LY2835219, Letrozole, Anastrozole, Tamoxifen, Exemestane
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LY2835219Drug

    Also called Abemaciclib

    Administered orally.

  • LetrozoleDrug

    Administered orally.

  • AnastrozoleDrug

    Administered orally.

  • TamoxifenDrug

    Administered orally.

  • ExemestaneDrug

    Administered orally.

  • EverolimusDrug

    Administered orally.

  • TrastuzumabDrug

    Administered IV infusion.

  • LY3023414Drug

    Administered orally.

  • FulvestrantDrug

    Administered IM.

  • PertuzumabDrug

    Administered IV infusion.

  • LoperamideDrug

    Administered orally.

  • Endocrine therapyDrug

    Endocrine therapy administered orally.

Study groups in NCT02057133
Study groupRoleWhat they receive
LY2835219 + LetrozoleExperimentalLY2835219 administered orally. Letrozole administered orally. This arm is closed to enrollment.
Receives: Drug: LY2835219; Drug: Letrozole
LY2835219 + AnastrozoleExperimentalLY2835219 administered orally. Anastrozole administered orally. This arm is closed to enrollment.
Receives: Drug: LY2835219; Drug: Anastrozole
LY2835219 + TamoxifenExperimentalLY2835219 administered orally. Tamoxifen administered orally. This arm is closed to enrollment.
Receives: Drug: LY2835219; Drug: Tamoxifen
LY2835219 + ExemestaneExperimentalLY2835219 administered orally. Exemestane administered orally. This arm is closed to enrollment.
Receives: Drug: LY2835219; Drug: Exemestane
LY2835219 + Exemestane + Everolimus Dose EscalationExperimentalLY2835219 administered orally. Exemestane administered orally. Everolimus administered orally. This arm is closed to enrollment.
Receives: Drug: LY2835219; Drug: Exemestane; Drug: Everolimus
LY2835219 + Exemestane + Everolimus Dose ExpansionExperimentalLY2835219 administered orally. Exemestane administered orally. Everolimus administered orally. This arm is closed to enrollment.
Receives: Drug: LY2835219; Drug: Exemestane; Drug: Everolimus
LY2835219+ Trastuzumab Dose EscalationExperimentalLY2835219 administered orally. Trastuzumab administered intravenously (IV) infusion. This arm is closed to enrollment.
Receives: Drug: LY2835219; Drug: Trastuzumab
LY2835219+ Trastuzumab Dose ExpansionExperimentalLY2835219 administered orally. Trastuzumab administered IV infusion. This arm is closed to enrollment.
Receives: Drug: LY2835219; Drug: Trastuzumab
LY3023414 + LY2835219 + Fulvestrant Dose EscalationExperimentalLY3023414 administered orally. LY2835219 administered orally. Fulvestrant administered intramuscularly (IM).
Receives: Drug: LY2835219; Drug: LY3023414; Drug: Fulvestrant
LY3023414 + LY2835219 + Fulvestrant Dose ExpansionExperimentalLY3023414 administered orally. LY2835219 administered orally. Fulvestrant administered IM.
Receives: Drug: LY2835219; Drug: LY3023414; Drug: Fulvestrant
LY2835219 +Trastuzumab +Pertuzumab +Loperamide Dose EscalationExperimentalLY2835219 administered orally. Loperamide administered orally. Trastuzumab administered IV infusion. Pertuzumab administered IV infusion.
Receives: Drug: LY2835219; Drug: Trastuzumab; Drug: Pertuzumab; Drug: Loperamide
LY2835219 +Trastuzumab + Pertuzumab +Loperamide Dose ExpansionExperimentalHormone 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.
Receives: Drug: LY2835219; Drug: Trastuzumab; Drug: Pertuzumab; Drug: Loperamide; Drug: Endocrine therapy
LY2835219 + Endocrine TherapyExperimentalLY2835219 administered orally. Ongoing endocrine therapy administered orally.
Receives: Drug: LY2835219; Drug: Endocrine therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants with One or More Drug-Related Adverse Events

    Number of participants with one or more drug-related adverse events

    Measured: Baseline through study completion (estimated as 12 months)

Secondary outcomes (5)

  1. Pharmacokinetics: Maximum Concentration (Cmax) of LY2835219, Letrozole, Anastrozole, Tamoxifen, Exemestane, Everolimus, Trastuzumab, LY3023414, Fulvestrant, and Pertuzumab

    Cmax of LY2835219, letrozole, anastrozole, tamoxifen, exemestane, everolimus, trastuzumab, LY3023414, fulvestrant, and pertuzumab.

    Measured: Cycle 1 up to Cycle 5 (21 or 28 Day Cycle): Predose and at multiple timepoints, depending on study part.

  2. Number of Participants with a Complete or Partial Tumor Response (Overall Response Rate)

    Number of participants with a complete or partial tumor response (overall response rate).

    Measured: Baseline to study completion (estimated as 12 months)

  3. Progression Free Survival (PFS)

    Progression free survival

    Measured: First dose to progressive disease or death of any cause (estimated as 12 months)

  4. Change in MD Anderson Symptom Inventory (MDASI) Score from Baseline

    Change in MD Anderson (MDASI) score from baseline.

    Measured: Baseline, through study completion (estimated as 12 months)

  5. Pharmacokinetics: Area under the Curve (AUC) of LY2835219, Letrozole, Anastrozole, Tamoxifen, Exemestane, Everolimus, Trastuzumab, LY3023414, Fulvestrant, and Pertuzumab

    Pharmacokinetics: AUC of LY2835219, letrozole, anastrozole, tamoxifen, exemestane, everolimus, trastuzumab, LY3023414, fulvestrant, and pertuzumab.

    Measured: Cycle 1 up to Cycle 5 (21 or 28 Day Cycle): Predose and at multiple timepoints, depending on study part.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Feb 2014 (estimated)
  2. Study start10 Mar 2014
  3. Primary completion15 Mar 2021
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
198 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02057133
Sponsor's protocol ID
15252
Other IDs
I3Y-MC-JPBH
Status last verified
Jan 2026
First submitted
4 Feb 2014
Last updated
26 Jan 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Expanded access
Available

Publications

  • 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.

    PubMed 35223458

  • 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.

    PubMed 24919854

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing LY2835219, Letrozole and Anastrozole in people with Breast Neoplasms, run by Eli Lilly and Company at 13 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 26 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants with One or More Drug-Related Adverse Events (time frame: Baseline through study completion (estimated as 12 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02057133, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2026.

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