PUMA-ALI-1201 is a randomized, dose optimization, multicenter, Phase 2 study of alisertib administered in combination with endocrine therapy in participants with pathology-confirmed HR-positive/HER2-negative metastatic breast cancer (MBC) following progression on or after at least two prior lines of endocrine therapy in the recurrent or metastatic setting. This study is intended to evaluate the optimal alisertib dose administered in combination with the selected endocrine therapy. The study is also planned to evaluate the efficacy, safety, and pharmacokinetics of alisertib in combination with endocrine and to identify the biomarker-defined subgroup(s) that may benefit most from combined alisertib and endocrine therapy. Participants randomized prior to Amendment 4 are randomized 1:1:1 to Arm 1, Arm 2 or Arm 3. Participants randomized under Amendment 4 will be randomized 1:1 to Arm 1 or Arm 2.
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.
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.
Parallel
Alisertib
DrugAlisertib 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
DrugInvestigator 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
Objective Response Rate (ORR) Within Dose Subgroup
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
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
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
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.
Objective Response Rate (ORR) Within Biomarker-Defined Subgroup
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
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
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
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.
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