Recruiting
Phase 2

Alisertib & Endocrine Therapy

Sponsor:

Puma Biotechnology, Inc.

Code:

NCT06369285

Conditions

Hormone Receptor Positive HER-2 Negative Breast Cancer

Metastatic Breast Cancer

Recurrent Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Alisertib

Endocrine therapy

Study Details

Brief summary:

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.

Conditions

Hormone Receptor Positive HER-2 Negative Breast Cancer

Metastatic Breast Cancer

Recurrent Breast Cancer

Study ID

NCT06369285

Start date

Nov 19, 2024

Status verified date

Jul, 2026

Completion date

Jun 30, 2029

Anticipated

Primary completion date

Dec 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

225 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Alisertib 50 mg

Alisertib with selected endocrine therapy

experimental: Alisertib 40 mg

Alisertib with selected endocrine therapy

experimental: Alisertib 30 mg

Alisertib with selected endocrine therapy

Interventions

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.

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

Primary outcome measure

  • Objective Response Rate (ORR) Within Dose Subgroup [ Time Frame: 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 [ Time Frame: From start date of response (after date of randomization) to first PD, assessed up to 48 months ]
  • Disease Control Rate (DCR) Within Dose Subgroup [ Time Frame: 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 [ Time Frame: From date of randomization to date of recurrence, progression or death, assessed up to 48 months ]
  • Overall Survival (OS) Within Dose Subgroup [ Time Frame: 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 [ Time Frame: From date of first dose through last dose plus 28 days, assessed up to 48 months ]

Central Contacts and Locations

Central contacts

Puma Biotechnology, Inc. Clinical Operations Senior Director

424-248-6500ClinicalTrials@pumabiotechnology.com

Locations

Alabama Oncology

Recruiting

Birmingham, Alabama, United States, 34235

Mayo Clinic Hospital

Recruiting

Phoenix, Arizona, United States, 85054

Beverly Hills Cancer Center

Recruiting

Beverly Hills, California, United States, 90211

MemorialCare Orange Coast Medical Center

Recruiting

Fountain Valley, California, United States, 92708

City of Hope at Orange County Lennar Foundation Cancer Center

Recruiting

Irvine, California, United States, 92618

LA Cancer Network

Recruiting

Los Angeles, California, United States, 90017

UCLA Department of Medicine - Hematology/Oncology

Recruiting

Los Angeles, California, United States, 90095

University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center

Recruiting

San Francisco, California, United States, 94158

University of Colorado School of Medicine

Recruiting

Aurora, Colorado, United States, 80045

Mayo Clinic Florida

Recruiting

Jacksonville, Florida, United States, 32224

Cancer Specialists of North Florida

Recruiting

Jacksonville, Florida, United States, 32256

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

Winship Cancer Institute, Emory University

Recruiting

Atlanta, Georgia, United States, 30322

University of Illinois Cancer Center

Recruiting

Chicago, Illinois, United States, 60612

The University of Chicago

Recruiting

Chicago, Illinois, United States, 60637

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

University of Minnesota, Masonic Cancer Center

Recruiting

Minneapolis, Minnesota, United States, 55455

Mayo Clinic

Recruiting

Rochester, Minnesota, United States, 55905

Missouri Cancer Associates

Recruiting

Columbia, Missouri, United States, 65201

Saint Luke's Cancer Institute

Recruiting

Kansas City, Missouri, United States, 64111

Oncology Hematology Associates

Recruiting

Springfield, Missouri, United States, 65807

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Cancer Care Specialists

Recruiting

Reno, Nevada, United States, 89511

University of Rochester Medical Center

Recruiting

Rochester, New York, United States, 14642

UNC Hospitals, University of North Carolina at Chapel Hill

Recruiting

Chapel Hill, North Carolina, United States, 27514

The Ohio State University, Stefanie Spielman Comprehensive Breast Center

Recruiting

Columbus, Ohio, United States, 43212

Taylor Cancer Research Center

Recruiting

Maumee, Ohio, United States, 43537

Alliance Cancer Specialists

Recruiting

Horsham, Pennsylvania, United States, 19044

University of Pennsylvania, Abramson Cancer Center, Perelman Center for Advanced Medicine

Recruiting

Philadelphia, Pennsylvania, United States, 19104

University of Pittsburgh (UPMC)

Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Tennessee Oncology, Greco-Hainsworth Center for Research

Recruiting

Nashville, Tennessee, United States, 37203

Texas Oncology

Recruiting

Dallas, Texas, United States, 75246

Virginia Cancer Institute

Recruiting

Richmond, Virginia, United States, 23229

More Information

Sponsor

Puma Biotechnology, Inc.

Last update posted

Jul 27, 2026

Last verified

Jul, 2026

Keywords

  • Hormone receptor positive (HR+)
  • Human epidermal growth factor receptor 2 negative (HER2-)
  • Recurrent Breast Cancer
  • Metastatic Breast Cancer

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Puma Biotechnology, Inc. on 2026-07-27.