A Study of Alisertib in Combination With Endocrine Therapy in Patients With HR-positive, HER2-negative Recurrent or Metastatic Breast Cancer (ALISCA-Breast1)

A Phase 2 Study of Alisertib in Combination With Endocrine Therapy in Patients With HR+, HER2-negative Recurrent or Metastatic Breast Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer; Recurrent Breast Cancer; Hormone Receptor Positive HER-2 Negative Breast Cancer
• Intervention / Treatment: Drug: Alisertib; Drug: Endocrine therapy

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Puma Biotechnology, Inc. Clinical Operations Senior Director; Phone Number: 424-248-6500; Email: ClinicalTrials@pumabiotechnology.com

Study Locations

• Portugal
  • Lisbon, Portugal, 1400-038
    • Recruiting
    • Fundacao Champalimaud
  • Lisbon, Portugal, 1998-018
    • Recruiting
    • Hospital CUF Descobertas
  • Lisbon, Portugal, 1099-023
    • Recruiting
    • Instituto Português de Oncologia de Lisboa Francisco Gentil (IPO Lisboa)
  • Porto, Portugal, 4200-072
    • Recruiting
    • Instituto Português Oncologia Do Porto
• Spain
  • Alicante, Spain, 03010
    • Recruiting
    • Hospital General Universitario Dr. Balmis
  • Barakaldo, Spain, 48903
    • Recruiting
    • Hospital Universitario de Cruces
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clínico de Barcelona
  • Bilbao, Spain, 48013
    • Recruiting
    • Hospital Universitario de Basurto
  • Cáceres, Spain, 10003
    • Recruiting
    • Hospital San Pedro de Alcántara
  • Granada, Spain, 18012
    • Recruiting
    • Hospital San Cecilio
  • Huelva, Spain, 21005
    • Recruiting
    • Hospital Universitario Juan Ramon Jimenez
  • Jaén, Spain, 23007
    • Recruiting
    • Hospital Universitario de Jaén
  • Lleida, Spain, 25198
    • Recruiting
    • Hospital Universitario Arnau de Vilanova
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Universitario Fundacion Jimenez Díaz
  • Seville, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46010
    • Recruiting
    • Hospital Clínico Universitario de Valencia
  • Valencia, Spain, 46009
    • Recruiting
    • Fundacion Instituto Valenciano de Oncologia (IVO)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 34235
      • Recruiting
      • Alabama Oncology
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Recruiting
      • Mayo Clinic Hospital
  • California
    • Beverly Hills, California, United States, 90211
      • Recruiting
      • Beverly Hills Cancer Center
    • Fountain Valley, California, United States, 92708
      • Recruiting
      • MemorialCare Orange Coast Medical Center
    • Irvine, California, United States, 92618
      • Recruiting
      • City of Hope at Orange County Lennar Foundation Cancer Center
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA Department of Medicine - Hematology/Oncology
    • Los Angeles, California, United States, 90017
      • Recruiting
      • LA Cancer Network
    • San Francisco, California, United States, 94158
      • Recruiting
      • University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado School of Medicine
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Withdrawn
      • Yale University, Yale Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Recruiting
      • Cancer Specialists of North Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Winship Cancer Institute, Emory University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • University of Illinois Cancer Center
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • The University of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota, Masonic Cancer Center
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Recruiting
      • Missouri Cancer Associates
    • Kansas City, Missouri, United States, 64111
      • Recruiting
      • Saint Luke's Cancer Institute
    • Springfield, Missouri, United States, 65807
      • Recruiting
      • Oncology Hematology Associates
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
  • Nevada
    • Reno, Nevada, United States, 89511
      • Recruiting
      • Cancer Care Specialists
  • New York
    • Rochester, New York, United States, 14642
      • Recruiting
      • University of Rochester Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Recruiting
      • UNC Hospitals, University of North Carolina at Chapel Hill
  • Ohio
    • Columbus, Ohio, United States, 43212
      • Recruiting
      • The Ohio State University, Stefanie Spielman Comprehensive Breast Center
    • Maumee, Ohio, United States, 43537
      • Recruiting
      • Taylor Cancer Research Center
  • Pennsylvania
    • Horsham, Pennsylvania, United States, 19044
      • Recruiting
      • Alliance Cancer Specialists
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania, Abramson Cancer Center, Perelman Center for Advanced Medicine
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh (UPMC)
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology, Greco-Hainsworth Center for Research
  • Texas
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Texas Oncology
  • Virginia
    • Richmond, Virginia, United States, 23229
      • Recruiting
      • Virginia Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged ≥18 years at signing of informed consent.
• Pathology-confirmed diagnosis of adenocarcinoma of the breast 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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alisertib 50 mg; Alisertib with selected endocrine therapy	Drug: Alisertib; 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.; Other Names: MLN8237; PB-8237; Drug: Endocrine therapy; 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
Experimental: Alisertib 40 mg; Alisertib with selected endocrine therapy	Drug: Alisertib; 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.; Other Names: MLN8237; PB-8237; Drug: Endocrine therapy; 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
Experimental: Alisertib 30 mg; Alisertib with selected endocrine therapy	Drug: Alisertib; 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.; Other Names: MLN8237; PB-8237; Drug: Endocrine therapy; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months
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.	From start date of response (after date of randomization) to first PD, assessed up to 48 months
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.	From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months
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.	From date of randomization to date of recurrence, progression or death, assessed up to 48 months
Overall Survival (OS) Within Dose Subgroup	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.	From date of randomization to death, assessed up to 48 months
Percentage of Participants With Treatment-Emergent Adverse Events (Adverse Events and Serious Adverse Events) in the Enrolled Population	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.	From date of first dose through last dose plus 28 days, assessed up to 48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months
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.	From start date of response (after date of randomization) to first PD, assessed up to 48 months
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.	From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months
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.	From date of randomization to date of recurrence, progression or death, assessed up to 48 months
Overall Survival (OS) Within Biomarker-Defined Subgroup	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.	From date of randomization to death, assessed up to 48 months

Collaborators and Investigators

• Sponsor: Puma Biotechnology, Inc.
• Investigators: Study Director: Chief Reg Affairs, PV, Medical Affairs and Law Officer, Puma Biotechnology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: April 12, 2024
• First Submitted That Met QC Criteria: April 12, 2024
• First Posted (Actual): April 16, 2024

Study Record Updates

• Last Update Posted (Actual): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Metastatic Breast Cancer; Recurrent Breast Cancer; Hormone receptor positive (HR+); Human epidermal growth factor receptor 2 negative (HER2-)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; MLN 8237
• Other Study ID Numbers: PUMA-ALI-1201; 2024-511497-79-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Puma Biotechnology is committed to sharing clinical trial data and information to help physicians and patients make informed treatment decisions, and to help qualified researchers advance scientific knowledge.

In accordance with legal and regulatory requirements, Puma publishes study protocol information and clinical study results on clinical trial registries, including ClinicalTrials.gov and EU Clinical Trials Register. Puma also publishes information about clinical studies in peer-reviewed scientific journals and shares data in scientific meetings.

Puma commits to safeguarding confidentiality and patient privacy throughout the clinical trial data and information sharing process. Any patient-level data will be anonymized to protect personally identifiable information.

Qualified researchers and study participants may submit requests for other study documentation and clinical trial data to clinicaltrials@pumabiotechnology.com for consideration.

• IPD Sharing Time Frame: Clinical study documents and clinical trial data may be requested by qualified researchers and study participants for studies that have been completed for at least 18 months, and for which the indication of the drug has been approved in the US and/or EU, as applicable. Requests will be accepted for up to 24 months after the criteria described in this section are met.

IPD Sharing Access Criteria

Requestors must provide organizational contact information; a detailed research plan, including outcomes; timeline for completion of the research; qualifications of the research team; funding source; and potential conflicts of interest.

Puma will not provide access to patient-level data if there is a reasonable likelihood that individual patients could be identified, or in cases where confidentiality or consent provisions prohibit transfer of data or information to third parties. Additionally, Puma will not disclose information that jeopardizes intellectual property rights or divulges confidential commercial information.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No