Clinical Trials /

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

NCT02513472

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate the Efficacy and Safety of Eribulin Mesylate in Combination With Pembrolizumab in Subjects With Metastatic Triple-Negative Breast Cancer (mTNBC)
  • Official Title: An Open-Label, Single-Arm Multicenter Phase 1b/2 Study to Evaluate the Efficacy and Safety of Eribulin Mesylate in Combination With Pembrolizumab in Subjects With Metastatic Triple-Negative Breast Cancer (mTNBC)

Clinical Trial IDs

  • ORG STUDY ID: E7389-M001-218
  • SECONDARY ID: KEYNOTE-150
  • NCT ID: NCT02513472

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
Eribulin MesylateHalaven, E7389Eribulin Mesylate + Pembrolizumab
PembrolizumabKeytruda, MK-3475Eribulin Mesylate + Pembrolizumab

Purpose

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

Detailed Description

      The Phase 1b part will evaluate the safety and tolerability of eribulin mesylate in
      combination with pembrolizumab. Approximately 6 participants may be enrolled in the Phase 1b
      part of the study. The Phase 2 part will evaluate the tumor objective responses when treated
      with eribulin mesylate in combination with pembrolizumab in participants with mTNBC
      previously treated with 0 to 2 lines of systemic anticancer therapy (cytotoxic or targeted
      anticancer agents) in the metastatic setting. Approximately 106 mTNBC participants (including
      participants in Phase 1b who are on RP2D level) will be enrolled in Phase 2.
    

Trial Arms

NameTypeDescriptionInterventions
Eribulin Mesylate + PembrolizumabExperimentalParticipants with metastatic triple-negative breast cancer (mTNBC) previously treated with 0 to 2 lines of systemic anticancer therapy (cytotoxic or targeted anticancer agents) in the metastatic setting
  • Eribulin Mesylate
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Females or males, aged greater than or equal to 18 years at the time of signing the
             informed consent form (ICF)

          2. Metastatic triple-negative breast cancer (confirmed from most recent tissue sample)
             meeting the following criteria:

               1. Estrogen receptor (ER) and progesterone receptor negative (a tumor is ER and/or
                  progesterone receptor positive if at least 1% of the cells examined have estrogen
                  and/or progesterone receptors) and human epidermal growth factor receptor 2
                  (HER2) negative (defined as immunohistochemistry [IHC] <2+ or fluorescence in
                  situ hybridization [FISH] negative).

               2. 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 (eg, bisphosphonates, denosumab, etc) are not considered
                  forms of systemic anticancer therapy.

          3. Presence of measurable disease meeting the following criteria:

               1. At least 1 lesion of greater than or equal to 10 mm in long axis diameter for
                  nonlymph nodes or greater than or equal to 15 mm in short axis diameter for lymph
                  nodes that is serially measurable according to RECIST 1.1 using computerized
                  tomography or magnetic resonance imaging or panoramic and close-up color
                  photography

               2. Lesions that have had radiotherapy must show subsequent radiographic evidence of
                  increased size to be deemed a target lesion

          4. Life expectancy of greater than or equal to 3 months

          5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

          6. Adequate renal function as evidenced by serum creatinine less than or equal to 1.5
             mg/dL or calculated creatinine clearance greater than or equal to 50 mL/minute
             according to the Cockcroft and Gault formula

          7. Adequate bone marrow function, defined as:

               1. Absolute neutrophil count (ANC) greater than or equal to 1.5 X 10^9/L

               2. Hemoglobin (Hb) greater than or equal to 10.0 g/dL (can be corrected by growth
                  factor or transfusion)

               3. Platelet count greater than or equal to 100 X 10^9/L

          8. Adequate liver function, defined as:

               1. Total bilirubin less than or equal to 1.5 X upper limit of normal (ULN)

               2. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate
                  aminotransferase (AST) ≤3 × ULN unless there are bone metastases, in which case
                  liver specific alkaline phosphatase must be separated from the total and used to
                  assess the liver function instead of the total alkaline phosphatase. ALT and AST
                  ≤ 5 × ULN if subject has liver metastases

          9. Resolution of all chemotherapy-related or radiation-related toxicities to Grade 1
             severity or lower, except for stable sensory neuropathy (less than or equal to Grade
             2) and alopecia

         10. Archived tissue sample or new biopsy sample

         11. Females must not be lactating or pregnant at Screening or Baseline (as documented by a
             negative beta-human chorionic gonadotropin [B-hCG] (or human chorionic gonadotropin
             [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units of B-hCG [or
             hCG]). A separate baseline assessment is required if a negative screening pregnancy
             test was obtained more than 72 hours before the first dose of study drug.

         12. All females will be considered to be of childbearing potential unless they are
             postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age
             group, and without other known or suspected cause) or have been sterilized surgically
             (ie, bilateral tubal ligation, total hysterectomy or bilateral oophorectomy, all with
             surgery at least 1 month before dosing)

         13. Females of childbearing potential must not have had unprotected sexual intercourse
             within 30 days before study entry and must agree to use a highly effective method of
             contraception (eg, total abstinence, an intrauterine device, a double-barrier method
             [such as condom plus diaphragm with spermicide], a contraceptive implant, a
             combination oral contraceptive (estrogen/progesterone), or have a vasectomized partner
             with confirmed azoospermia) throughout the entire study period and for 120 days after
             study drug discontinuation. If currently abstinent, the subject must agree to use a
             double barrier method as described above if she becomes sexually active during the
             study period or for 120 days after study drug discontinuation. Females who are using
             hormonal contraceptives must have been on a stable dose of the same hormonal
             contraceptive product for at least 28 days before dosing and must continue to use the
             same contraceptive during the study and for 120 days after study drug discontinuation.

         14. Males who have had a successful vasectomy (confirmed azoospermia) or they and their
             female partners meet the criteria above (ie, not of childbearing potential or
             practicing highly effective contraception throughout the study period or for 120 days
             after study drug discontinuation). No sperm donation is allowed during the study
             period or for 120 days after study drug discontinuation.

         15. Willing and able to comply with all aspects of the treatment protocol

         16. Provide written informed consent

        Exclusion Criteria:

          1. Previous treatment with eribulin mesylate or any anti-PD-1, PD-L1, or PD-L2

          2. Active autoimmune disease that has required systemic treatment in the past 2 years
             (ie, with use of disease modifying agents, corticosteroids, or immunosuppresive
             drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a
             form of systemic treatment.

          3. Less than 6 months since prior adjuvant chemotherapy

          4. Current enrollment in another interventional clinical study or used any
             investigational drug or device within the past 28 days preceding informed consent

          5. Treatment with chemotherapy or biological therapy within the previous 3 weeks,
             radiation or small molecule targeted therapy within the previous 2 weeks

          6. Known central nervous system (CNS) disease, except for those subjects 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 (magnetic
             resonance imaging [MRI] or computed tomography [CT]) during the screening period

          7. Known history of human immunodeficiency virus (HIV) positive

          8. Known active hepatitis B (eg, HBsAg reactive) or hepatitis C (eg, HCV RNA detected)

          9. Existing anticancer treatment-related toxicities of Grades greater than or equal to 2
             (except for alopecia and Grade 2 sensory neuropathy) according to Common Terminology
             Criteria for Adverse Events (CTCAE v4.03)

         10. 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

         11. History of significant cardiovascular disease, defined as:

               1. congestive heart failure greater than New York Heart Association (NYHA) Class II
                  according to the NYHA Functional Classification

               2. unstable angina or myocardial infarction within 6 months of enrollment

               3. serious cardiac arrhythmia

         12. 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 greater than 500 ms)

         13. History of concomitant medical conditions or infectious diseases that, in the opinion
             of the investigator, would compromise the subject's ability to safely complete the
             study

         14. Hypersensitivity to the active substance or any other excipients of the eribulin
             mesylate drug product, or or severe hypersensitivity (≥Grade 3) to pembrolizumab
             and/or any of its excipients

         15. Scheduled for major surgery during the study

         16. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
             The use of physiologic doses of corticosteroids may be approved after consultation
             with the sponsor

         17. Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis

         18. Has a history of interstitial lung disease

         19. Has an active infection requiring systemic therapy

         20. Has received a live-virus vaccination within 30 days of planned start of study
             therapy. Seasonal flu vaccines that do not contain live virus are permitted.

         21. The investigator's belief that the subject is medically unfit to receive eribulin
             mesylate and pembrolizumab or unsuitable for any other reason
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicity (DLT)
Time Frame:Up to 1 cycle (21 days) in Phase 1b part
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Progression-Free Survival (PFS)
Time Frame:From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurs first, or up to approximately 38 months
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:From date of first dose of study drug administration until date of death from any cause or up to approximately 38 months
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:From the date that a confirmed OR is first documented to the date of progressive disease (PD) or death due to any cause for those subjects with a confirmed PR (partial response) or CR (complete response) or up to approximately 38 months
Safety Issue:
Description:
Measure:Clinical Benefit Rate (CBR)
Time Frame:From the date that is confirmed BOR (best overall response) of CR complete response),PR (partial response) or durable stable disease(SD) (≥ 24Weeks)
Safety Issue:
Description:
Measure:ORR in the PD-L1 positive subset
Time Frame:From date of first dose of study drug administration up to 38 months
Safety Issue:
Description:
Measure:PFS in the PD-L1 positive subset
Time Frame:From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurs first, or up to approximately 38 months
Safety Issue:
Description:
Measure:OS in the PD-L1 positive subset
Time Frame:From date of first dose of study drug administration until date of death from any cause or up to approximately 38 months
Safety Issue:
Description:
Measure:DOR in the PD-L1 positive subset
Time Frame:From the date that a confirmed OR is first documented to the date of PD or death due to any cause for those subjects with a confirmed PR or CR or up to approximately 38 months
Safety Issue:
Description:
Measure:CBR in the PD-L1 positive subset
Time Frame:From date of the first dose of the study drug administration up to 38 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eisai Inc.

Trial Keywords

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

Last Updated

January 2, 2018