A Randomized Phase II Study Of Eribulin Mesylate With or Without Pembrolizumab For Metastatic Hormone Receptor Positive Breast Cancer

NCT03051659 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 16-577
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is exploring chemotherapy in combination with immunotherapy (a therapy that uses the body's own immune system to control cancer) as a possible treatment for metastatic hormone receptor positive breast cancer.

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Median Progression Free Survival (PFS)

  Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

  Disease assessments is performed every 3 cycles (3 weeks/cycle) for the first 18 cycles. Median follow-up 10.5 months with range 0.43-19 months.

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  Disease assessments is performed every 3 cycles (3 weeks/cycle) for the first 18 cycles. If after Cycle 18 scans, a participant has SD or better by RECIST the frequency of assessments may be reduced to every 4 cycles, up to a maximum of 18 months.

• Median Overall Survival (OS)

  Disease assessments is performed every 3 cycles (3 weeks/cycle) for the first 18 cycles. Median follow-up 10.5 months with range 0.43-19 months.

• Median Duration of Response (DOR)

  Disease assessments is performed every 3 cycles (3 weeks/cycle) for the first 18 cycles. If after Cycle 18 scans, a participant has SD or better by RECIST the frequency of assessments may be reduced to every 4 cycles.

• Clinical Benefit Rate (CBR)

  Disease assessments is performed every 3 cycles (3 weeks/cycle) for the first 18 cycles. If after Cycle 18 scans, a participant has SD or better by RECIST the frequency of assessments may be reduced to every 4 cycles, up to a maximum of 18 months.

• Number of Participants With Grade 3 or Higher Treatment-Related Toxicity

  Disease assessments is performed every 3 cycles (3 weeks/cycle) for the first 18 cycles. If after Cycle 18 scans, a participant has SD or better by RECIST the frequency of assessments may be reduced to every 4 cycles, up to a maximum of 18 months.

Study Arms (2)

Eribulin Mesylate

EXPERIMENTAL

-Eribulin mesylate will be administered on Days 1 and 8 of each 21 day cycle for 1.4mg/m\^2 intravenously.

Drug: Eribulin Mesylate

Eribulin Mesylate Combine with Pembrolizumab

EXPERIMENTAL

* Pembrolizumab will be administered in clinic once per cycle, given 200mg/m\^2 intravenously prior to Eribulin Mesylate. * Eribulin mesylate will be administered on Days 1 and 8 of each 21 day cycle for 1.4 mg/m\^2 intravenously.

Drug: Eribulin Mesylate; Drug: Pembrolizumab

Interventions

Eribulin Mesylate DRUG

Eribulin mesylate is developed from a natural substance found in a sea sponge. Eribulin mesylate works by preventing cancer cells from multiplying

Also known as: Halaven

Eribulin Mesylate; Eribulin Mesylate Combine with Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells.

Also known as: Keytruda

Eribulin Mesylate Combine with Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed Stage IV invasive breast cancer. Patients without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation.
• Subjects must have at least one lesion that is not within a previously radiated field that is evaluable on computerized tomography (CT) or magnetic resonance imaging (MRI) scan per RECIST version 1.1. If the subject's only evaluable disease is within a previously radiated field, it must have demonstrated progression since the time of radiation.
• Participants must have HR positive, HER2-negative breast cancer (ER\>1% and/or, PR\>1%, HER2-negative per ASCO CAP guidelines, 2013 resulted on the primary tumor and/or a metastatic lesion).
• Participants must have already received or been intolerant to at least two lines of hormonal therapies (including the adjuvant or metastatic setting) or be appropriate candidates for chemotherapy
• Prior chemotherapy: Participants are allowed to have received up to 2 prior lines of chemotherapy in the metastatic setting. If a prior chemotherapy was given for less than 1 cycle, it will not be counted as a prior line. The last dose of chemotherapy must be ≥14 days prior to initiation of study therapy. Participants should be adequately recovered from acute toxicities of prior treatment. No prior treatment with eribulin mesylate is allowed.
• Prior biologic therapy: The last dose of biologic or investigational therapy must be ≥21 days prior to initiation of study therapy.
• Prior hormonal therapy: Hormonal therapy must have been discontinued ≥14 days prior to initiation of study therapy. However, continuation of ovarian suppression is allowed.
• Prior radiation therapy: Participants may have received prior radiation therapy in either the metastatic or early-stage setting. Radiation therapy must be completed ≥14 days prior to initiation of study therapy.
• Prior targeted therapy: Targeted therapy must have been discontinued ≥ 14 days prior to initiation of study therapy.
• Biphosphonates/Denosumab: Participants on bisphosphonates/denosumab may continue receiving bisphosphonate therapy during study treatment.
• Participants must have an archival tumor sample available (1 block or 20 unstained slides). If no archival tissue is available, participants must be willing to undergo a research biopsy of their disease if it is safely accessible.
• Age ≥ 18 years of age
• ECOG performance status ≤2 (Karnofsky ≥60%)
• Participants must have normal organ and marrow function as defined below:
• absolute neutrophil count ≥1,500/mcL

You may not qualify if:

• Chemotherapy-related or radiation-related toxicities that have not resolved to Grade 1 severity or lower, except for stable sensory neuropathy (≤ Grade 2) and alopecia.
• Participants who are receiving any other investigational agents.
• Previous treatment with eribulin mesylate or any anti-PD-1, PD-L1, or PD-L2 agent or participation in any MK-3475 Merck studies.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to eribulin mesylate or pembrolizumab.
• Known 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 4 weeks prior to registration, are neurologically stable and absence of new neurologic symptoms for the last 4 weeks prior to study entry, and have recovered from the 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 deemed appropriate by the treating physician.
• Uncontrolled intercurrent illness, including, but not limited to uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, congestive heart failure-New York Heart Association Class III or IV, active ischemic heart disease, myocardial infarction within the previous six months, uncontrolled diabetes mellitus, gastric or duodenal ulceration diagnosed within the previous 6 months, chronic liver or renal disease, severe malnutrition or psychiatric illness/social situations that would limit compliance with study requirements.
• Clinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolonged QT/QTc (\[QT interval/corrected QT interval\], eg, a repeated demonstration of a QTc interval \>500 ms).
• Medcial condition that requires chronic systemic steroid therapy or on any other form of immunosuppressive medication. For example, participants with autoimmune disease that requires systemic steroids or immunosuppression agents should be excluded. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• History or evidence of active, noninfectious pneumonitis that required treatment with steroids.
• History of interstitial lung disease.
• Participants known to be positive for the human immunodeficiency virus (HIV), Hepatitis B antigen (HepBsAg), or Hepatitis C virus (HCV) RNA. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Pembrolizumab and/or eribulin mesylate. In addition, these participants are at increased risk of lethal infections.
• 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 diagnosed and treated 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 study sponsor to determine eligibility.
• Has received a live vaccine within 28 days of planned start of study therapy.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (2)

• Keenan TE, Guerriero JL, Barroso-Sousa R, Li T, O'Meara T, Giobbie-Hurder A, Tayob N, Hu J, Severgnini M, Agudo J, Vaz-Luis I, Anderson L, Attaya V, Park J, Conway J, He MX, Reardon B, Shannon E, Wulf G, Spring LM, Jeselsohn R, Krop I, Lin NU, Partridge A, Winer EP, Mittendorf EA, Liu D, Van Allen EM, Tolaney SM. Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer. Nat Commun. 2021 Sep 21;12(1):5563. doi: 10.1038/s41467-021-25769-z.

  PMID: 34548479 DERIVED

• Tolaney SM, Barroso-Sousa R, Keenan T, Li T, Trippa L, Vaz-Luis I, Wulf G, Spring L, Sinclair NF, Andrews C, Pittenger J, Richardson ET 3rd, Dillon D, Lin NU, Overmoyer B, Partridge AH, Van Allen E, Mittendorf EA, Winer EP, Krop IE. Effect of Eribulin With or Without Pembrolizumab on Progression-Free Survival for Patients With Hormone Receptor-Positive, ERBB2-Negative Metastatic Breast Cancer: A Randomized Clinical Trial. JAMA Oncol. 2020 Oct 1;6(10):1598-1605. doi: 10.1001/jamaoncol.2020.3524.

  PMID: 32880602 DERIVED

MeSH Terms

Conditions

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: Sara Tolaney, MD, MPH
• Organization: Dana-Farber Cancer Institute

Sara_Tolaney@dfci.harvard.edu

(877) 442-3324

Study Officials

• Sara Tolaney, MD MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigaor

Study Record Dates

• First Submitted: February 8, 2017
• First Posted: February 14, 2017
• Study Start: March 22, 2017
• Primary Completion: October 11, 2018
• Study Completion: September 5, 2023
• Last Updated: March 6, 2024
• Results First Posted: May 11, 2022

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)