Ph II Study of Pembrolizumab & Eribulin in Patients With HR+/HER2- MBC Previously Treated With Anthracyclines & Taxanes

NCT03222856 | Completed Phase 2 Results

• 2 other identifiers: MedOPP1272016-004513-27
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 11

Brief Summary

This a multicenter, open-label, phase II clinical trial to assess the efficacy of pembrolizumab in combination with eribulin in female patients older than 18 years old with hormone receptor-(HR)positive/HER2-negative metastatic breast cancer (MBC) previously treated with at least one, but not more than two, prior chemotherapeutic regimens for treatment of locally recurrent and/or metastatic disease. Prior therapy must have included an anthracycline and a taxane and prior anti-hormonal therapy is mandatory. The number of patients to be included is 44 patients at 11 sites. All eligible patients will be treated with MK3475 (pembrolizumab) 200 mg on day 1 of each 21-day cycle and eribulin 1.23 mg/m2 (equivalent to eribulin mesylate at 1.4 mg/m2) on days 1 and 8 of every 21-day cycle.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Efficacy of Pembrolizumab in Combination With Eribulin.

  The efficacy -as determined by the clinical benefit rate (CBR) (total number of objective responses plus stable disease for at least 24 weeks) based on RECIST v.1.1- of MK3475 (pembrolizumab) in combination with eribulin in patients with HR-positive/HER2-negative MBC who have previously received an anthracycline and a taxane (for either early or advanced disease), unless contraindicated, and between one to two lines of chemotherapy in the metastatic setting. Per Response Evaluation Criteria In Solid Tumors (RECIST v1.1) for target lesions: Complete Response (CR) is defined as the disappearance of all target lesions. Partial Response (PR) is defined as a decrease of ≥30% in the sum of the longest diameter of target lesions. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as Progressive Disease (PD).

  Through study completion. From baseline up to 36 months.

Secondary Outcomes (10)

• The CBR in Subjects With Programmed Death Ligand-1 (PD-L1) Positive Tumors.

  Through study completion. From baseline up to 36 months.

• The Progression-free Survival (PFS)

  Through study completion. From baseline up to 36 months.

• The PFS in Subjects With PD-L1 Positive Tumors.

  Through study completion. From baseline up to 36 months.

• Overall Survival (OS)

  From baseline up to 36 months.

• The OS in Subjects With PD-L1 Positive Tumors.

  Through study completion. From baseline up to 36 months.

Other Outcomes (3)

• Gene Signature Predictive of MK3475 (Pembrolizumab) and Eribulin Therapy Benefit.

  24 months

• The Link Between Mutational Load and Response to MK3475 (Pembrolizumab) and Eribulin.

  24 months

• PD-L1 Expression in Circulating Tumor Cells (CTCs) and Its Correlation With Response to MK3475 (Pembrolizumab) and Eribulin.

  Through study completion. From baseline up to 36 months.

Study Arms (1)

Pembrolizumab + eribulin

EXPERIMENTAL

All eligible patients will be treated with MK3475 (pembrolizumab) 200 mg on day 1 of each 21-day cycle and eribulin 1.23 mg/m2 (equivalent to eribulin mesylate at 1.4 mg/m2) on days 1 and 8 of every 21-day cycle. Treatment with MK3475 (pembrolizumab) and eribulin will continue based on physician criteria. No maximum duration of treatment is specified. Study follow-up will be performed 12 months after last study dose.

Drug: Pembrolizumab; Drug: Eribulin

Interventions

Pembrolizumab DRUG

MK3475 (pembrolizumab) will be supplied directly as a solution for infusion in a single-use vial. Each vial contains 100 mg of MK3475 (pembrolizumab) in 4 ml of solution.

Also known as: Keytruda, MK3475

Pembrolizumab + eribulin

Eribulin DRUG

Eribulin will be supplied as a clear and colourless aqueous solution for injection provided in glass vials containing 2 ml. Each 2 ml vial contains eribulin mesylate equivalent to 0.88 mg eribulin.

Also known as: Halaven

Pembrolizumab + eribulin

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female patients age ≥ 18 years with advanced HR-positive/HER2- negative breast cancer previously treated with anthracyclines and taxanes.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent prior to beginning specific protocol procedures.
• Female patients ≥18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1 which the Investigator believes is stable at the time of screening.
• Life expectancy ≥ 12 weeks.
• Patients have a histologically and/or cytologically confirmed diagnosis of breast cancer.
• Patients have radiologic evidence of inoperable locally recurrent or MBC.
• Patients have HER2-negative breast cancer (based on most recently analyzed biopsy) defined as a negative in situ hybridization (ISH) test or an immunohistochemistry (IHC) status of 0, 1+, or 2+ (if IHC 2+, a negative ISH test is required) by local laboratory testing.
• Patients have HR-positive breast cancer defined as estrogen receptor (ER) and/or progesterone receptor (PR) with \>1% of tumor cells positive for ER and/or PR by IHC irrespective of staining intensity.
• Available tumor tissue for PD-L1 biomarker analysis from a newly obtained core or excisional biopsy since last progression of a metastatic tumor lesion not previously irradiated.
• Note: Subjects for whom tumor biopsies cannot be obtained (e.g., inaccessible tumor or subject safety concern) may submit an archived metastatic tumor specimen only upon agreement from the Sponsor.
• Patients have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 as assessed by site Investigator and local radiology review.
• Patients have received at least one, but not more than two, prior chemotherapeutic regimens for locally recurrent and/or metastatic disease. Prior therapy must have included an anthracycline and a taxane in any combination or order and either in the early or metastatic disease setting unless contraindicated for a given patient. Prior anti-hormonal therapy is mandatory.
• Patients have adequate bone marrow and organ function as defined by the following laboratory values:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L.
• Platelets ≥ 100 x 10\^9/L.

You may not qualify if:

• Patients have received previous treatment with eribulin and an/or anti-PD1 or anti-PD-L1 agents.
• Patients have a known hypersensitivity to any of the excipients of MK3475 (pembrolizumab) or eribulin.
• Patients who have received chemotherapy, targeted small molecule therapy, or radiotherapy within two weeks of first dose of study treatment.
• Patients who have received monoclonal antibodies for direct antineoplastic treatment or an investigational agent/device within four weeks of first dose of study treatment.
• Patients have known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Note: Known brain metastases are considered active, if any of the following criteria is applicable:
• Brain imaging during screening demonstrates progression of existing metastases and/or appearance of new lesions compared to brain imaging performed at least four weeks earlier.
• Neurological symptoms attributed to brain metastases have not returned to baseline.
• Steroids were used for brain metastases within 28 days of first dose of study treatment.
• Patients have peripheral neuropathy grade 2 or more.
• Patients have a concurrent malignancy or malignancy within five years of study enrollment (with the exception of adequately treated, basal or squamous cell skin carcinoma or curatively resected cervical cancer).
• Patients have not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy.
• Patients have had a major surgical procedure within 28 days prior to starting study drug.
• Patients have an active cardiac disease or a history of cardiac dysfunction including any of the following:
• Unstable angina pectoris or documented myocardial infarction within six months prior to study entry.

Sponsors & Collaborators

• MedSIR: lead

Study Sites (11)

Corporació Sanitaria Sanitari Parc Taulí

Sabadell, Barcelona, Spain

Location

Hospital de Navarra

Pamplona, Navarre, Spain

Location

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Spain

Location

Instituto Oncológico Baselga - Hospital Quirónsalud Barcelona

Barcelona, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

MD Anderson

Madrid, Spain

Location

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

Hospital Arnau de Vilanova de Valencia

Valencia, Spain

Location

Hospital Clínico de Valencia

Valencia, Spain

Location

Related Publications (1)

• Perez-Garcia JM, Llombart-Cussac A, G Cortes M, Curigliano G, Lopez-Miranda E, Alonso JL, Bermejo B, Calvo L, Caranana V, de la Cruz Sanchez S, M Vazquez R, Prat A, R Borrego M, Sampayo-Cordero M, Segui-Palmer MA, Soberino J, Malfettone A, Schmid P, Cortes J. Pembrolizumab plus eribulin in hormone-receptor-positive, HER2-negative, locally recurrent or metastatic breast cancer (KELLY): An open-label, multicentre, single-arm, phase Ⅱ trial. Eur J Cancer. 2021 May;148:382-394. doi: 10.1016/j.ejca.2021.02.028. Epub 2021 Mar 29.

  PMID: 33794440 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pembrolizumab; eribulin

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

There were not enough events in the SOC arm (patients discharged) to estimate the upper limit of the 95% confidence interval in the Duration of Response (DoR) endpoints.

Results Point of Contact

• Title: Scientific Director
• Organization: MedSIR

alicia.garcia@medsir.org

+34 611261467

Study Officials

• Javier Cortés, PhD

  MedSIR

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A phase II, multicenter, open-label study of pembrolizumab and eribulin in patients with HR- positive/HER2-negative metastatic breast cancer previously treated with anthracyclines and taxanes.

Study Record Dates

• First Submitted: July 13, 2017
• First Posted: July 19, 2017
• Study Start: December 14, 2017
• Primary Completion: October 31, 2018
• Study Completion: December 23, 2020
• Last Updated: June 5, 2025
• Results First Posted: February 19, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (11)