Study to Evaluate the Efficacy and Safety of Eribulin Mesylate in Combination With Pembrolizumab in Participants With Metastatic Triple-Negative Breast Cancer (mTNBC)

NCT02513472 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: E7389-M001-218KEYNOTE-150
• Study Type: interventional
• Target: 258
• Locations: 1 country
• Sites: 22

Brief Summary

This is an open-label, single-arm, multicenter, Phase 1b/2 study of eribulin mesylate in combination with pembrolizumab in participants with mTNBC previously treated with 0 (stratum 1) or 1 to 2 (stratum 2) lines of systemic anticancer therapy (cytotoxic or targeted anticancer agents) in the metastatic setting.

Conditions

Breast Neoplasm

Keywords

Eribulin Mesylate; Pembrolizumab; Metastatic Triple-Negative Breast Cancer; mTNBC

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR was defined as percentage of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR) using independent imaging review (IIR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. BOR of CR and PR was confirmed by a subsequent CR assessment and CR or PR assessment, respectively at least 4 weeks later. CR: disappearance of all measurable, non-measurable lesions and no unequivocal new lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (\<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in sum of diameters (SOD) of target lesions, taking as reference the baseline SOD and there are no unequivocal new lesions, and no progression of non-target disease. The 2-sided 95% confidence interval (CI) calculated by Clopper-Pearson method. As planned, data up to the primary completion date only were analyzed.

  From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurred first (up to 3 years 11 months)

Secondary Outcomes (8)

• Progression-free Survival (PFS)

  From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurred first (up to 3 years 11 months)

• Overall Survival (OS)

  From date of first dose of study drug administration until date of death from any cause (up to 3 years 11 months)

• Duration of Response (DOR)

  From the date that a confirmed objective response (OR) was first documented to the date of PD or death due to any cause for those participants with a confirmed PR or CR (up to 3 years 11 months)

• Clinical Benefit Rate (CBR)

  From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurred first (up to 3 years 11 months)

• ORR in the Programmed Death Receptor-Ligand 1 (PD-L1) Positive Set

  From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurred first (up to 3 years 11 months)

Other Outcomes (1)

• CBR in the PD-L1 Positive Set

  From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurred first (up to 3 years 11 months)

Study Arms (1)

Eribulin Mesylate + Pembrolizumab

EXPERIMENTAL

Participants with mTNBC previously treated with 0 (stratum 1) or 1 to 2 (stratum 2) lines of systemic anticancer therapy (cytotoxic or targeted anticancer agents) in the metastatic setting.

Drug: Eribulin Mesylate; Drug: Pembrolizumab

Interventions

Eribulin Mesylate DRUG

Eribulin Mesylate will be administered as a 1.4 milligram per square meter (mg/m\^2) IV (intravenous) infusion on Day 1 and Day 8 of each 21-day cycle in the presence of clinical benefit until intercurrent illness, unacceptable toxicity, or disease progression occurs, or until the participant withdraws consent.

Also known as: Halaven, E7389

Eribulin Mesylate + Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab will be administered as a 200 milligram (mg) IV infusion on Day 1 of each 21-day cycle in the presence of clinical benefit until intercurrent illness, unacceptable toxicity, or disease progression occurs, or until the participant withdraws consent.

Also known as: Keytruda, MK-3475

Eribulin Mesylate + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Females or males, aged \>=18 years at the time of signing the informed consent form (ICF).
• mTNBC (confirmed from most recent tissue sample) meeting the following criteria:
• Estrogen receptor (ER) and progesterone receptor negative (a tumor is ER and/or progesterone receptor positive if at least 1 percent (%) of the cells examined have estrogen and/or progesterone receptors) and human epidermal growth factor receptor 2 (HER2) negative (defined as immunohistochemistry \[IHC\] less than (\<) 2+ or fluorescence in situ hybridization \[FISH\] negative).
• Previously treated with 0 to 2 lines of systemic anticancer therapy (cytotoxic or targeted anticancer agents) in the metastatic setting. Hormonal therapy and bone metastases treatment (example, bisphosphonates, denosumab, etc) are not considered forms of systemic anticancer therapy.
• Presence of measurable disease meeting the following criteria:
• At least 1 lesion of \>=10 millimeter (mm) in long axis diameter for nonlymph nodes or \>=15 mm in short axis diameter for lymph nodes that is serially measurable according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) using computerized tomography (CT) or magnetic resonance imaging (MRI) or panoramic and close-up color photography.
• Lesions that have had radiotherapy must show subsequent radiographic evidence of increased size to be deemed a target lesion.
• Life expectancy of \>=3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Adequate renal function as evidenced by serum creatinine less than or equal to (\<=) 1.5 milligram per deciliter (mg/dL) or calculated creatinine clearance \>=50 millimeter per minute (mL/min) according to the Cockcroft and Gault formula.
• Adequate bone marrow function, defined as:
• Absolute neutrophil count (ANC) \>=1.5\*10\^9/L.
• Hemoglobin (Hb) \>=10.0 gram per deciliter (g/dL) (can be corrected by growth factor or transfusion).
• Platelet count \>=100\*10\^9/L.
• Adequate liver function, defined as:

You may not qualify if:

• Previous treatment with eribulin mesylate or any anti-programmed death receptor-1 (anti-PD-1), programmed death receptor ligand-1 (PD-L1), or PD-L2 agent.
• Active autoimmune disease that has required systemic treatment in the past 2 years (that is, with use of disease modifying agents, corticosteroids, or immunosuppresive drugs). Replacement therapy (example, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment.
• Less than 6 months since prior adjuvant chemotherapy.
• Current enrollment in another interventional clinical study or used any investigational drug or device within the past 28 days preceding informed consent.
• Treatment with chemotherapy or biological therapy within the previous 3 weeks, radiation or small molecule targeted therapy within the previous 2 weeks.
• Known central nervous system (CNS) disease, except for those participants with treated brain metastasis who are stable for at least 1 month, having no evidence of progression or hemorrhage after treatment and no ongoing requirement for corticosteroids, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period.
• Known history of human immunodeficiency virus (HIV) positive.
• Known active hepatitis B (example, HBsAg reactive) or hepatitis C (example, hepatitis C virus ribonucleic acid (HCV RNA) detected).
• Existing anticancer treatment-related toxicities of Grades \>= 2 (except for alopecia and Grade 2 sensory neuropathy) according to Common Terminology Criteria for Adverse Events (CTCAE v4.03).
• Any other malignancy that required treatment or has shown evidence of recurrence (except for nonmelanoma skin cancer, or histologically confirmed complete excision of carcinoma in situ) during the 5 years prior to enrollment in this study.
• History of significant cardiovascular disease, defined as:
• congestive heart failure greater than New York Heart Association (NYHA) Class II according to the NYHA Functional Classification.
• unstable angina or myocardial infarction within 6 months of enrollment.
• serious cardiac arrhythmia.
• Clinically significant electrocardiogram (ECG) abnormality, including a marked Baseline prolonged QT interval/corrected QT interval (\[QT/QTc\], example, a repeated demonstration of a QTc interval \>500 millisecond \[ms\]).

Sponsors & Collaborators

• Eisai Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (22)

Facility #1

Duarte, California, 91010, United States

Location

Facility #1

Santa Barbara, California, 93105, United States

Location

Facility #1

Denver, Colorado, 80218, United States

Location

Facility #1

Miami, Florida, 33176, United States

Location

Facility #1

West Palm Beach, Florida, 33401, United States

Location

Facility #1

Boston, Massachusetts, 02115, United States

Location

Facility #2

Boston, Massachusetts, 02115, United States

Location

Facility #1

Minneapolis, Minnesota, 55407, United States

Location

Facility #1

St Louis, Missouri, 63110, United States

Location

Facility #1

Lebanon, New Hampshire, 03756, United States

Location

Facility #1

New York, New York, 10032, United States

Location

Facility #2

New York, New York, 10065, United States

Location

Facility #1

Chattanooga, Tennessee, 37404, United States

Location

Facility #1

Nashville, Tennessee, 37203, United States

Location

Facility #1

Austin, Texas, 78731, United States

Location

Facility #1

Fort Worth, Texas, 76104, United States

Location

Facility #1

San Antonio, Texas, 78217, United States

Location

Facility #2

San Antonio, Texas, 78229, United States

Location

Facility #1

Sherman, Texas, 75090, United States

Location

Facility #1

Salem, Virginia, 24153, United States

Location

Facility #1

Winchester, Virginia, 22601, United States

Location

Facility #1

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

eribulin; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_oncmedinfo@eisai.com

1-888-274-2378

Study Officials

• Dr. Claudio Savulsky

  Eisai Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2015
• First Posted: July 31, 2015
• Study Start: August 28, 2015
• Primary Completion: July 31, 2019
• Study Completion: April 6, 2021
• Last Updated: May 5, 2022
• Results First Posted: August 14, 2020

Record last verified: 2022-04

Locations

US (22)