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LY3023414 and Prexasertib in Metastatic Triple-negative Breast Cancer

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ClinicalTrials.gov Identifier: NCT04032080
Recruitment Status : Active, not recruiting
First Posted : July 25, 2019
Last Update Posted : July 20, 2022
Eli Lilly and Company
Information provided by (Responsible Party):
Baylor Research Institute

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

Condition or disease Intervention/treatment Phase
Triple Negative Breast Cancer Combination Product: Drug 1: LY3023414; Drug 2: Prexasertib Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Patients with metastatic TNBC who meet the enrollment criteria will receive LY3023414 and prexasertib until disease progression.
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : September 5, 2019
Actual Primary Completion Date : June 1, 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: LY3023414 + prexasertib
Patients 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.
Combination Product: Drug 1: LY3023414; Drug 2: Prexasertib

Metastatic TNBC patients will consent to and undergo core needle biopsies of a metastatic lesion for NGS, RPPA, and other molecular analyses at study entry.

Patients will then be treated with 150 mg LY3023414 PO BID and prexasertib 80 mg/m^2 IV administered every 2 weeks until disease progression or unacceptable toxicity. Any time after the completion of Cycle 2 of the treatment combination, or at the physician's discretion, a second core needle biopsy of the same metastatic lesion (or different metastases if the initial metastasis has regressed) will be performed for RPPA and other molecular analyses. If a research biopsy from a patient's metastatic disease cannot be safely obtained, a skin biopsy is permitted.

Treatment will be discontinued in patients who achieve a confirmed clinical complete response, and these patients will be followed to document the durability of the complete responses.

Primary Outcome Measures :
  1. Efficacy (objective response rate) [ Time Frame: Through study completion, 18 months ]
    To assess the objective response rate (CR+PR) associated with LY3023414 and prexasertib in metastatic TNBC patients.

Secondary Outcome Measures :
  1. Efficacy (duration of response) [ Time Frame: through study completion, 18 months] ]
    To assess duration of response to combination of LY3023414 and prexasertib in metastatic TNBC patients.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 permitted.
  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 discretion.
  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 C).
    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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04032080

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United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
Sponsors and Collaborators
Baylor Research Institute
Eli Lilly and Company
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Principal Investigator: Joyce A O'Shaughnessy, MD Baylor Scott and White University Medical Center
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Responsible Party: Baylor Research Institute
ClinicalTrials.gov Identifier: NCT04032080    
Other Study ID Numbers: 018-745
First Posted: July 25, 2019    Key Record Dates
Last Update Posted: July 20, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases