Abemaciclib in Treating Patients with Rb Positive Triple-Negative Breast Cancer That is Recurrent, Locally Advanced, Metastatic, or Cannot Be Removed by Surgery

Status: Active


This phase II trial studies how well abemaciclib works in treating patients with retinoblastoma (Rb) positive triple-negative breast cancer that has come back (recurrent), has spread to other places in the body (metastatic), or cannot be removed by surgery. Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Eligibility Criteria

Inclusion Criteria

  • Patients must have histologically or cytologically confirmed invasive breast cancer, which is recurrent, locally advanced, unresectable or metastatic
  • Patients must have at least one lesion that is not within a previously radiated field and that is measurable per RECIST version 1.1; bone lesions are not considered measurable
  • Either the primary tumor and/or metastatic tumor must be triple-negative as defined below: * Hormone receptor status: the invasive tumor must be estrogen receptor (ER)- and progesterone receptor (PR)- negative, or staining present in < 1% by immunohistochemistry (IHC) * HER2 status: the invasive tumor must be human epidermal growth factor receptor 2 negative (HER2-negative) by the American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines * In cases where both primary tumor and metastatic sample(s) have been tested for ER, PR, and HER2, then the triple-negative status of the tumor should be determined from the most recent sample available
  • Either the primary tumor and/or the metastatic tumor must be RB positive as defined below: * RB status: the invasive tumor must have greater than 50% of tumor cells staining positive for RB
  • Prior chemotherapy: * Patients may have received 1-3 prior therapies for metastatic disease (note: for patients who have first developed recurrent/metastatic disease within 12 months of completing any [neo]-adjuvant therapy for triple-negative breast cancer, the [neo]-adjuvant therapy is counted as a prior line of therapy) * Patients must have been off treatment with myelosuppressive chemotherapy for at least 21 days or nonmyelosuppressive agents for 14 days before registration; patients should also be adequately recovered (to baseline or grade 1) from acute toxicities of prior treatment except for residual alopecia and peripheral neuropathy
  • Prior biologic therapy: Patients must have discontinued all biologic therapy at least 21 days before registration
  • Patients may have received prior radiation therapy in either the metastatic or early-stage setting; radiation therapy must be completed at least 7 days prior to study registration
  • Patients on bisphosphonates or RANK-L inhibitors may continue receiving these therapies during study treatment; there is no washout period required between the last dose of these therapies and the start of abemaciclib
  • The patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count >= 1500/mm^3
  • Platelets >= 100,000/mm^3
  • Hemoglobin >= 8 g/dL * Note: Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator; initial treatment must not begin earlier than the day the after the erythrocyte infusion
  • Total Bilirubin =< 1.5 x the upper limit of normal (ULN) or =< 2.0 x the upper limit of normal (ULN) in patients with documented Gilbert’s syndrome
  • Serum creatinine =< 1.5 mg/dL OR calculated glomerular filtration rate (GFR) >= 60 mL/min
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 times the upper limit of normal; for patients with documented liver metastases, AST/ALT =< 5.0 times the upper limit of normal
  • Female subjects of childbearing potential must have a negative serum pregnancy test at screening; women of childbearing potential are defined as those who have not been surgically sterilized and have had a menstrual period in the past year
  • Capable of understanding and complying with the protocol and has signed the informed consent document
  • Able to swallow study drug
  • Sexually active patients (male and female) must use medically acceptable methods of contraception during the course of the study and for 3 months after completion of study treatment; if a woman becomes pregnant or suspects she is pregnant while participating in this study, she should inform her treating physician immediately; while on the study and for 3 months after final drug administration, women may not breast-feed
  • Confirmed availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue
  • Patients with tumor that is felt to be accessible to biopsy must be willing to provide tissue from a newly obtained core biopsy of a tumor lesion at baseline; biopsies will be obtained up to 1 week (7 days) prior to initiation of treatment on cycle 1, day 1; patients who undergo an attempted research biopsy procedure for the purpose of this protocol, and in whom inadequate tissue is obtained, are not required to undergo a repeat biopsy in order to continue on protocol

Exclusion Criteria

  • Received a prior CDK4/6 inhibitor
  • Undergone major surgery within 14 days of the initial dose of study drug
  • Received another investigational agent (defined as any agent/device that has not received regulatory approval for any indication) within 14 days of the first dose of study drug for a nonmyelosuppressive agent, or 21 days of the first dose of study drug for a myelosuppressive agent
  • Has any severe concurrent disease, infection, or comorbid condition that renders the patient inappropriate for enrollment in the opinion of the investigator
  • Has an active bacterial infection (requiring IV antibiotics at the time of initiating study treatment), fungal infection, or detectable viral infection; patients with known human immunodeficiency virus (HIV) infection are excluded given the potential for interactions between antiretroviral agents and abemaciclib, and the potential for increased risk of life-threatening infection with therapy that is myelosuppressive; patients with known hepatitis B or hepatitis C infection are excluded only if there is evidence of active infection (detectable hepatitis B surface antigen, detectable hepatitis C ribonucleic acid [RNA])
  • Documented brain metastases that are untreated, symptomatic, or require therapy to control symptoms; participants with previously diagnosed brain metastases are eligible if they have completed treatment at least 7 days prior to trial registration, are neurologically stable, and have recovered from effects of radiotherapy or surgery * Any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for >= 2 weeks before the first study drug * Treatment for brain metastases may have included whole brain radiotherapy, radiosurgery, or a combination as was deemed appropriate by the treating physician * Patients who meet the above criteria and are clinically stable on anti-convulsant medication are eligible only if their anti-convulsant does not alter hepatic cytochrome P450 activity in a way that might interfere with metabolism of abemaciclib
  • Pregnant women are excluded from this study
  • Lactating women are excluding from the study
  • Individuals with a history of a second malignancy are ineligible except for the following circumstances: individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy; individuals with the following cancers are eligible if they are diagnosed and have completed treatment within the past 5 years: cervical cancer in situ, and non-melanoma cancer of the skin; patients with other cancers diagnosed within the past 5 years and felt to be at low risk of recurrence should be discussed with the principal investigator to determine eligibility
  • Have received any live vaccination within 28 days of first dose of study drug
  • Has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest

Locations & Contacts


Dana-Farber Cancer Institute
Status: Active
Contact: Sara Michell Tolaney
Phone: 617-632-2335
Email: stolaney@partners.org

Trial Objectives and Outline


I. To evaluate the efficacy of abemaciclib, as defined by objective response rate (ORR) in patients with Rb-positive triple-negative metastatic breast cancer (ORR as confirmed complete response [CR] or partial response [PR] per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1).


I. To evaluate abemaciclib with respect to progression-free survival (PFS).

II. To evaluate abemaciclib with respect to overall survival (OS).

III. To evaluate abemaciclib with respect to disease control rate (DCR).

IV. To evaluate abemaciclib with respect to clinical benefit rate (CBR).

V. To detect if there is a difference in clinical outcomes between patients with and without phospho-Rb reduction.


I. To explore additional potential biomarkers in blood and tumor tissue samples that might predict response or resistance to abemaciclib.

II. To determine the association between genomic alterations in tumor deoxyribonucleic acid (DNA) (mutations, copy number alterations, mutational burden) and RB expression and other tissue biomarkers by immunohistochemistry as well as response to abemaciclib.

III. To determine if there are any changes in the T-cell phenotype during exposure to abemaciclib.

IV. To explore changes in the microbiome induced by therapy comparing stool samples collected at baseline, during treatment, and at the time of progression.


Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of treatment, patients are followed up every 6 months.

Trial Phase & Type

Trial Phase

Phase II

Trial Type


Lead Organization

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Sara Michell Tolaney

Trial IDs

Primary ID 17-024
Secondary IDs NCI-2017-01192
Clinicaltrials.gov ID NCT03130439