Clinical Trials /

LY3023414 and Prexasertib in Metastatic Triple-negative Breast Cancer



This study evaluates efficacy of LY3023414 and prexasertib in patients with metastatic triple negative breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:



Phase 2

Trial Eligibility



  • Brief Title: LY3023414 and Prexasertib in Metastatic Triple-negative Breast Cancer
  • Official Title: Pilot Clinical Trial of Treatment With LY3023414 and Prexasertib to Inhibit Homologous Recombination (HR) in Patients With Chemotherapy-Pretreated Metastatic Triple Negative Breast Cancer (Amendment 1)

Clinical Trial IDs

  • ORG STUDY ID: 018-745
  • NCT ID: NCT04032080


  • Triple Negative Breast Cancer


This study evaluates efficacy of LY3023414 and prexasertib in patients with metastatic triple negative breast cancer.

Detailed Description

      Seventy to eighty percent of breast cancers have a gene expression profile which is
      characterized by homologous recombination deficiency (HRD) and high proliferation. HRD leads
      to errors in DNA pathway [non -homologous end joining (NHEJ)] that repair DNA-breaks, a
      process required for metastatic triple negative breast cancer (TNBC) survival. The hypothesis
      of this pilot trial is that administration of LY3023414 and prexasertib will inhibit NHEJ in
      metastatic TNBC.

Trial Arms

LY3023414 + prexasertibExperimentalPatients with metastatic TNBC who meet the enrollment criteria will receive LY3023414 and prexasertib until disease progression. Patients whose disease does not respond to the combination of LY3023414 and prexasertib may be treated with standard of care breast cancer therapies off study, at the recommendation of the treating physician.

    Eligibility Criteria

            Inclusion Criteria:
              1. Patients ≥18 years of age. Patients must agree to use one highly effective (less than
                 1% failure rate) method of contraception or use a combination of two effective methods
                 of contraception during treatment with study drug and for at least 12 weeks following
                 the last dose of study drug.
              2. Have a diagnosis of metastatic TNBC previously treated with standard anthracycline,
                 cyclophosphamide, and taxane chemotherapy, unless there was a contraindication to
                 doxorubicin, in which case prior treatment with this agent is not required. NOTE: TNBC
                 defined as ER-negative tumors with ≤10% tumor nuclei immunoreactivity, or "ER Low
                 Positive" as defined by the updated ASCO/CAP guidelines 2020.
              3. Have not received more than 3 prior chemotherapy regimens for metastatic disease.
                 Prior platinum and/or taxane therapy in the adjuvant or metastatic setting is
              4. Have locoregional (eg, breast, chest wall, regional lymphatic) or pulmonary or hepatic
                 metastatic disease that is amenable to core needle biopsy. If a research biopsy from a
                 patient's metastatic disease cannot be safely obtained, a skin biopsy is permitted. If
                 a skin biopsy cannot be safely obtained, patients may still be eligible, per physician
              5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
              6. Have adequate hematologic function, defined by:
                   1. Absolute neutrophil count (ANC) >1500/mm^3
                   2. Platelet count ≥100,000/mm^3
                   3. Hemoglobin ≥9 g/dL
              7. Have adequate liver function, defined by:
                   1. AST and ALT ≤2.5 x the upper limit of normal (ULN) or ≤5 x ULN in presence of
                      liver metastases
                   2. Total bilirubin ≤1.5 x ULN
              8. Have adequate renal function, defined by:
                 a. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance of ≥60 ml/min
              9. Have the ability to swallow oral medications
             10. Patients who have a history of brain metastasis are eligible for the study provided
                 that all the following criteria are met:
                   1. Brain metastases which have been treated
                   2. Off-treatment with steroids for 2 weeks before administration of the first dose
                      of LY3023414 and prexasertib
                   3. No ongoing requirement for dexamethasone or anti-epileptic drugs
                   4. No clinical or radiological evidence of progression of brain metastases
             11. Patient must be accessible for treatment and follow-up.
             12. All patients must be able to understand the investigational nature of the study and
                 give written informed consent prior to study entry.
            Exclusion Criteria:
              1. Have a family history of long QT Syndrome and serious cardiac conditions.
              2. Have QTcF interval of >470 msec on screening electrocardiogram (ECG) as well as on
                 pre-dose Cycle 1 Day 1 ECG
              3. Have insulin-dependent diabetes mellitus. Patients with a type 2 diabetes mellitus are
                 eligible if adequate control of blood glucose level is obtained by oral anti-diabetics
                 as documented by HbA1c <8%. Patients with type 1 diabetes mellitus are not eligible.
              4. Previous radiotherapy for metastatic disease completed <2 weeks prior to study
                 treatment initiation.
              5. Women who are pregnant or lactating.
              6. Patients who have any severe and/or uncontrolled medical conditions or other
                 conditions that could affect their participation such as:
                   1. severe impaired lung functions as defined as spirometry and DLCO that is 50% of
                      the normal predicted value and/or O2 saturation that is 88% or less at rest on
                      room air
                   2. liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class
                   3. viral hepatitis or HIV.
              7. Concurrent use of CYP3A4 inhibitors and inducers from 72 hours prior to initiation of
                 study treatment until the end of treatment.
              8. History of any other disease, physical examination finding, or clinical laboratory
                 finding giving reasonable suspicion of a disease or condition that contraindicates use
                 of an investigational drug, or that might affect interpretation of the results of this
                 study, or render the patient at high risk for treatment complications.
              9. Patients who have received prior PI3K or CHK therapy.
             10. Any other investigational or anti-cancer treatments while participating in this study
             11. Any other active malignancy.
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Efficacy (objective response rate)
    Time Frame:Through study completion, 18 months
    Safety Issue:
    Description:To assess the objective response rate (CR+PR) associated with LY3023414 and prexasertib in metastatic TNBC patients.

    Secondary Outcome Measures

    Measure:Efficacy (duration of response)
    Time Frame:through study completion, 18 months]
    Safety Issue:
    Description:To assess duration of response to combination of LY3023414 and prexasertib in metastatic TNBC patients.


    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Baylor Research Institute

    Last Updated

    March 26, 2021