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RECRUITING

NCT05696626

PHASE3

Evaluation of Lasofoxifene Combined With Abemaciclib Compared With Fulvestrant Combined With Abemaciclib in Locally Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation

Sponsor: LeonaBio

View on ClinicalTrials.gov

Summary

The goal of this clinical trial is to assess the efficacy, safety and tolerability of the combination of lasofoxifene and abemaciclib compared to fulvestrant and abemaciclib for the treatment of pre- and postmenopausal women and men who have previously received ribociclib or palbociclib-based treatment and have locally advanced or metastatic estrogen receptor positive (ER+)/human epidermal growth factor 2 negative (HER2-) breast cancer with an estrogen receptor 1 (ESR1) mutation. The main question the study aims to answer is: • To compare the efficacy of the combination of lasofoxifene and abemaciclib with that of fulvestrant and abemaciclib Participants will receive either receive 5 mg/d of oral lasofoxifene plus oral abemaciclib 150 mg twice a day or the combination of fulvestrant 500 mg intramuscular (IM) on Days 1, 15, and 29 and then once monthly thereafter plus oral abemaciclib 150 mg twice a day.

Official title: An Open Label, Randomized, Multicenter Study Comparing the Efficacy and Safety of the Combination of Lasofoxifene and Abemaciclib to the Combination of Fulvestrant and Abemaciclib for the Treatment of Pre- and Postmenopausal Women and Men With Locally Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

600

Start Date

2023-10-31

Completion Date

2028-04

Last Updated

2026-10-29

Healthy Volunteers

Conditions

Metastatic Breast Cancer

Interventions

DRUG

Lasofoxifene in combination with abemaciclib

5 mg/d of oral lasofoxifene plus oral abemaciclib 150 mg twice a day

DRUG

Fulvestrant in combination with abemaciclib

Fulvestrant 500 mg intramuscular (IM) on Days 1, 15, and 29 and then once monthly thereafter plus oral abemaciclib 150 mg twice a day

Inclusion Criteria: 1. Pre- or postmenopausal women or men. 2. Locally advanced and/or metastatic ER+ breast cancer with radiological or clinical evidence of progression on an AI in combination with either palbociclib or ribociclib as their first hormonal treatment for metastatic disease. 3. Histological or cytological confirmation of ER+/HER2 - disease 4. No evidence of progression for at least 6 months on an AI/CDKi combination for advanced breast cancer. 5. At least 1 or more ESR1 point mutations in the ESR1 ligand binding domain as assessed in cell- free ctDNA obtained from a blood or breast cancer tissue. 6. Locally advanced or metastatic breast cancer with at least 1 measurable (according to RECIST 1.1) lesion with or without non-measurable lesions. 7. Subjects may have received 1 cytotoxic chemotherapy regimen in the metastatic disease setting prior to study entry, but must have recovered from chemotherapy acute toxicity excluding alopecia and Grade 2 peripheral neuropathy. 8. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 9. Adequate organ function 10. Able to swallow tablets 11. Brain metastases are allowed only if the following 4 parameters hold: 1. Asymptomatic, 2. Definitively treated (e.g., radiotherapy, surgery), 3. Not requiring steroids up to 4 weeks before study treatment initiation, AND 4. Central nervous system disease stable for \>3 months prior to registration as documented by magnetic resonance imagining (MRI). 12. Able to understand and voluntarily sign a written informed consent before any screening procedures. 13. Every attempt should be made to obtain a biopsy of metastatic breast cancer tissue, when safe and feasible, to provide histological or cytological confirmation of ER+/HER2- disease as assessed by a local laboratory, according to American Society of Clinical Oncology/College of American Pathologists guidelines, using slides, paraffin blocks, or paraffin samples. If a biopsy is done, it may undergo genomic testing at some point to assess for ESR1 mutations and correlation with ctDNA results. If a biopsy is not possible or inappropriate from a clinical standpoint, the ER and HER2 status from the subject's most recent biopsy must confirm that the subject is ER+ and HER2 Exclusion Criteria: 1. Lymphangitic carcinomatosis involving the lung. 2. History of Grade 3 or Grade 4 interstitial lung disease (ILD) on previous therapy. 3. Visceral crisis in need of cytotoxic chemotherapy as assessed by the investigator. 4. Prior progression of disease on abemaciclib, fulvestrant, or other selective estrogen receptor degrader (SERD) therapy. 5. Subjects with a known hypersensitivity to fulvestrant or to any of the excipients 6. Radiotherapy within 30 days prior to Visit 0 (Day 1) except in case of localized radiotherapy for analgesic purposes or for lytic lesions at risk of fracture, which can then be completed within 7 days prior to Visit 0 (Day 1). Subjects must have recovered from radiotherapy toxicities prior to Visit 0 (Day 1). 7. Known RB1 mutations or deletions that in the opinion of the investigator confer resistance to CDK4/6i. (Screening for RB1 mutation is not required for entry.) 8. History of long QTc (Q-T interval corrected for heart rate) syndrome or a QTc of \>480 msec. 9. History of a pulmonary embolus (PE), deep vein thrombosis (DVT), or any known thrombophilia, unless the event occurred greater than 6 months prior to screening and the subject is treated with chronic anticoagulant therapy such as apixaban (Eliquis) or rivaroxaban (Xarelto). 10. Lasofoxifene is not recommended for use in subjects with conditions that place them at increased risk for VTEs (such as severe congestive heart failure \[CHF\] or prolonged immobilization). 11. On concomitant strong CYP3A4 inhibitors. 12. On strong and moderate CYP3A4 inducers. 13. Any significant co-morbidity that would impact the study or the subject's safety, including subjects with significant malabsorption. 14. Active systemic bacterial or fungal infection (requiring intravenous \[IV\] antibiotics or antifungals at the time of initiating study treatment). 15. Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). 16. History of malignancy within the past 5 years (excluding breast cancer), except basal cell or squamous cell carcinoma of the skin curatively treated by surgery. 17. Positive serum pregnancy test (only if premenopausal). 18. Sexually active premenopausal women and men unwilling to use double-barrier contraception. 19. Women who are breast feeding 20. History of non-compliance to medical regimens. 21. Unwilling or unable to comply with the protocol. 22. Current participation in any clinical research trial involving an investigational drug or device within the last 30 days. 23. Subjects with a history of familial hypertriglyceridemia or fasting triglyceride levels \>880 mg/dL at screening. 24. Fasting triglyceride level \>300 mg/dL and ≤880 mg/dL at screening. Subjects may be retested and enrolled if they have a repeat fasting triglyceride level less than or equal to 300 mg/dL prior to enrollment (e.g., after adjustment with diet and/or treatment). 25. Fasting cholesterol level \>400 mg/dL at screening. Subjects may be retested and enrolled if they have a repeat fasting cholesterol level less than or equal to 400 mg/dL prior to enrollment (e.g., after adjustment with diet and/or treatment).

Locations (224)

Mayo Clinic - Scottsdale

Scottsdale, Arizona, United States

University of Arizona - Cancer Center

Tucson, Arizona, United States

Providence Medical Foundation - Santa Rosa, CA

Santa Rosa, California, United States

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Miami Cancer Institute

Miami, Florida, United States

Miami Cancer Institute Plantation

Plantation, Florida, United States

Emory University School of Medicine

Atlanta, Georgia, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Johns Hopkins Kimmel Cancer Center

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Cancer and Hematology Centers of Western Michigan

Grand Rapids, Michigan, United States

Allina Health System DBA Virginia Piper Cancer Institute

Minneapolis, Minnesota, United States

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Saint Luke's Cancer Institute

Kansas City, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Renown Regional Medical Centre

Reno, Nevada, United States

Cancer Care Specialists

Reno, Nevada, United States

New Jersey Cancer Care, PA

Belleville, New Jersey, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Presbyterian Kaseman Hospital

Albuquerque, New Mexico, United States

Presbyterian Rust Cancer Center

Rio Rancho, New Mexico, United States

The Blavatnik Family - Chelsea Medical Center at Mount Sinai

New York, New York, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Altru Health Systems

Grand Forks, North Dakota, United States

University Hospitals Seidman Cancer Center

Cleveland, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solovev Research Institute (OSUCCC - James)

Columbus, Ohio, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Baylor College of Medicine

Houston, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

Harris Health System - Smith Clinic

Houston, Texas, United States

Swedish Cancer Institute (SCI)

Seattle, Washington, United States

Blacktown Hospital

Blacktown, Australia

Concord Repatriation General Hospital

Concord, Australia

Mater Misericordiae Ltd, South Brisbane

South Brisbane, Australia

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Antwerp University Hospital (UZA)

Edegem, Belgium

Universitaire Ziekenhuizen Leuven

Leuven, Belgium

CHU UCL Namur - Site De Sainte-Elisabeth

Namur, Belgium

The Ottawa General Hospital

Ottawa, Ontario, Canada

Sunnybrook Health Sciences Centre -Bayview Campus

Toronto, Ontario, Canada

Hospital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Lady Davis Institute for Medical Research Jewish General Hospital

Montreal, Quebec, Canada

CIUSSS du Saguenay-Lac-Saint-Jean

Saguenay, Quebec, Canada

Anhui Provincial Cancer Hospital

Anhui, China

Anyang Tumour Hospital

Anyang, China

Beijing Cancer Hospital

Beijing, China

Peking Union Medical College Hospital

Beijing, China

The First Affiliated Hospital of Bengbu Medical University

Bengbu, China

The First Hospital of Jilin University

Changchun, China

The Second Xiangya Hospital of Central South University

Changsha, China

Sichuan Provincial People's Hospital

Chengdu, China

West China Hospital, Sichuan University

Chengdu, China

The First Affiliated Hospital, Chongqing Medical University

Chongqicun, China

The Second Hospital of Dalian Medical University

Dalian, China

Deyang People's Hospital

Deyang, China

Fuyang Cancer Hosptial

Fuyang, China

Fujian Cancer Hospital

Fuzhou, China

Fujian Medical University Union Hospital

Fuzhou, China

Zhujiang Hospital of Nanfang Medical University

Guandong, China

Guangdong Provincial People's Hospital

Guangdong, China

Meizhou People's Hospital

Guangdong, China

Peking University Shenzhen Hospital

Guangdong, China

Sun Yat-Sen University- Cancer Center

Guangdong, China

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, China

The First Affiliated Hospital of Hainan Medical University

Haikou, China

Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University

Hangzhou, China

The First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, China

Zhejiang Provincial Hospital of Chinese Medicine

Hangzhou, China

Hebei Medical University - The Fourth Hospital - Hebei Provincial Tumor Hospital

Hebei, China

Xiangyang Central Hospital

Hubei, China

Xiangya Hospital Central South University

Hunan, China

Jieyang People's Hospital

Jieyang, China

Shandong Province Tumor Hospital

Jinan, China

Yunnan Cancer Hospital

Kunming, China

Gansu Provincial Hospital

Lanzhou, China

The First Hospital of Lanzhou University

Lanzhou, China

Linyi Cancer Hospital

Linyi, China

Luoyang Central Hospital

Luoyang, China

The First Affiliated Hospital of Henan University of Science and Technology

Luoyang, China

The Affiliated Hospital of Southwest Medical University (Luzhou Medical College)

Luzhou, China

Jiangxi Cancer Hospital

Nanchang, China

Nanchang People's Hospital

Nanchang, China

Jiangsu Province Hospital - The First Affiliated Hospital with Nanjing Medical University

Nanjing, China

Nanjing Drum Tower Hospital

Nanjing, China

Guangxi Medical University Cancer Hospital

Nanning, China

Nanyang Central Hospital

Nanyang, China

The Second People's Hospital of Neijiang

Neijiang, China

Ningbo Medical Center Li Huili Hospital

Ningbo, China

The First People'S Hospital of Ping Ding Shan

Pingdingshan, China

Qingdao Central Hospital, University of Health and Rehabilitation Sciences

Qingdao, China

The Affiliated Hospital of Qingdao University

Qingdao, China

Quanzhou First Hospital

Quanzhou, China

Huashan Hospital, Fudan University

Shanghai, China

Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, China

Fudan University Cancer Center

Shang’ai, China

And 124 more locations on ClinicalTrials.gov

Clinical Research Directory

Evaluation of Lasofoxifene Combined With Abemaciclib Compared With Fulvestrant Combined With Abemaciclib in Locally Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (224)