A Study of Alisertib in Combination With Endocrine Therapy in Patients With HR-positive, HER2-negative Recurrent or Metastatic Breast Cancer

• Alisertib (Drug), also known as PB-8237, MLN8237: Alisertib enteric-coated tablets will be taken by mouth twice daily on days 1-3, 8-10, and 15-17 of each 28-day cycle.
• Endocrine therapy (Drug): Investigator selected endocrine therapy will be taken in 28-day dosing cycles according to the approved prescribing information. 1 mg of anastrozole tablet by mouth once daily or 2.5 mg of letrozole tablet by mouth once daily or 25 mg of exemestane tablet by mouth once daily or 20 mg of tamoxifen tablet by mouth once daily or 500 mg of fulvestrant intramuscular injection on Study Day 1, 15, 29, and once every 28 days thereafter

Primary outcomes

• Objective Response Rate (ORR) Within Dose Subgroup [From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months]: Objective response rate is defined as the percentage of participants demonstrating a confirmed objective response during the study.
• Duration of Response (DOR) Within Dose Subgroup [From start date of response (after date of randomization) to first PD, assessed up to 48 months]: Duration of response is measured from the time at which measurement criteria are first met for Complete Response (CR) or Partial Response (PR) (whichever status is recorded first) until the first date of recurrence or progressive disease (PD) or death is objectively documented.
• Disease Control Rate (DCR) Within Dose Subgroup [From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months]: Disease control rate is the proportion of participants who achieve overall tumor response (confirmed CR or PR) or Stable Disease (SD) lasting for at least 24 weeks from randomization.
• Progression Free Survival (PFS) Within Dose Subgroup [From date of randomization to date of recurrence, progression or death, assessed up to 48 months]: Progression Free Survival (PFS) is measured in months and based on the local tumor assessment. The time interval from the date of randomization until the first date on which recurrence, progression, or death due to any cause, is documented.
• Overall Survival (OS) Within Dose Subgroup [From date of randomization to death, assessed up to 48 months]: Overall survival (OS) is defined as the time from randomization to death due to any cause, censored at the last date known alive on or prior to the data cutoff employed for the analysis, whichever was earlier.
• Percentage of Participants With Treatment-Emergent Adverse Events (Adverse Events and Serious Adverse Events) in the Enrolled Population [From date of first dose through last dose plus 28 days, assessed up to 48 months]: Treatment emergent adverse events are those events reported on or after the first dose of investigational product and up to 28 days after last dose.

Secondary outcomes

• Objective Response Rate (ORR) Within Biomarker-Defined Subgroup [From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months]: Objective response rate is defined as the percentage of participants demonstrating a confirmed objective response during the study.
• Duration of Response (DOR) Within Biomarker-Defined Subgroup [From start date of response (after date of randomization) to first PD, assessed up to 48 months]: Duration of response is measured from the time at which measurement criteria are first met for CR or PR (whichever status is recorded first) until the first date of recurrence or progressive disease (PD) or death is objectively documented.
• Disease Control Rate (DCR) Within Biomarker-Defined Subgroup [From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months]: Disease control rate is the proportion of participants who achieve overall tumor response (confirmed CR or PR) or SD lasting for at least 24 weeks from randomization.
• Progression Free Survival (PFS) Within Biomarker-Defined Subgroup [From date of randomization to date of recurrence, progression or death, assessed up to 48 months]: Progression Free Survival (PFS) is measured in months and based on the local tumor assessment. The time interval from the date of randomization until the first date on which recurrence, progression, or death due to any cause, is documented.
• Overall Survival (OS) Within Biomarker-Defined Subgroup [From date of randomization to death, assessed up to 48 months]: Overall survival (OS) is defined as the time from randomization to death due to any cause, censored at the last date known alive on or prior to the data cutoff employed for the analysis, whichever was earlier.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Aged ≥18 years at signing of informed consent.
* Pathology-confirmed diagnosis of breast cancer with evidence of recurrent or metastatic disease not amenable to curative therapy.
* Progression on or after treatment with at least two prior lines of endocrine therapy in the recurrent or metastatic setting. a. If metastatic disease recurrence occurs during or within six months of discontinuing adjuvant endocrine therapy, then that endocrine therapy will count as one line of prior therapy.
* Participants must have received a CDK4/6i in combination with endocrine therapy in the recurrent or metastatic setting.
* HR-positive and HER2-negative tumor status reported per local laboratory testing. HR and HER2 testing must be performed consistent with current American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) or European Society of Medical Oncology (ESMO) guidelines.

Exclusion Criteria:

* Treatment with chemotherapy in the recurrent or metastatic setting, including antibody drug conjugates with a chemotherapeutic payload.
* Prior treatment with an Aurora Kinase A (AURKA) specific-targeted or pan-Aurora-targeted agent, including alisertib, in any setting.

Note: There are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.

• Chief Reg Affairs, PV, Medical Affairs and Law Officer, Study director, Puma Biotechnology, Inc.