Clinical trial NCT05696626: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Metastatic Breast Cancer
Lead sponsor: Sermonix Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2023-01-25
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: open label, randomized, parallel-group, multicenter study
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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 either measurable (according to RECIST 1.1) or 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.

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.

Primary outcomes:
measure: Progression free survival (PFS)
timeFrame: Within approximately 3 years
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Within approximately 3 years
measure: Overall survival (OS)
timeFrame: Within approximately 3 years
measure: Clinical benefit rate (CBR)
timeFrame: Within approximately 3 years
measure: Duration of response (DoR) in subjects with an objective response
timeFrame: Within approximately 3 years
measure: Time to response (TTR) in subjects with an objective response
timeFrame: Within approximately 3 years
measure: Time to cytotoxic chemotherapy
timeFrame: Within approximately 3 years
measure: Quality of Life (QoL) evaluated using the Functional Assessment of Cancer Therapy-Breast Cancer-Endocrine Subscale (FACT B-ES)
timeFrame: Within approximately 3 years
measure: Incidence of Adverse Events (AEs) and Serious AEs
timeFrame: Within approximately 3 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic - Phoenix
state: Arizona
city: Tucson
country: United States
facility: University of Arizona - Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: California Research Institute
state: California
city: Santa Rosa
country: United States
facility: Providence Medical Foundation - Santa Rosa, CA
state: California
city: Boca Raton
country: United States
facility: Boca Raton Regional Hospital
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Plantation
country: United States
facility: Miami Cancer Institute Plantation
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Kimmel Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Grand Rapids
country: United States
facility: Cancer and Hematology Centers of Western Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Allina Health System DBA Virginia Piper Cancer Institute
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Reno
country: United States
facility: Renown Regional Medical Centre
state: Nevada
city: Belleville
country: United States
facility: New Jersey Cancer Care, PA
state: New Jersey
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Grand Forks
country: United States
facility: Altru Health Systems
state: North Dakota
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solovev Research Institute (OSUCCC - James)
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: Lyndon B. Johnson Hospital
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: Harris Health System - Smith Clinic
state: Texas
city: Blacktown
country: Australia
facility: Blacktown Hospital
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
city: South Brisbane
country: Australia
facility: Mater Misericordiae Ltd, South Brisbane
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Edegem
country: Belgium
facility: Antwerp University Hospital (UZA)
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
city: Namur
country: Belgium
facility: CHU UCL Namur - Site De Sainte-Elisabeth
city: Ottawa
country: Canada
facility: The Ottawa General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre -Bayview Campus
state: Ontario
city: Montréal
country: Canada
facility: Hospital Maisonneuve-Rosemont
state: Quebec
city: Montréal
country: Canada
facility: Lady Davis Institute for Medical Research Jewish General Hospital
state: Quebec
city: Saguenay
country: Canada
facility: CIUSSS du Saguenay-Lac-Saint-Jean
state: Quebec
city: Anhui
country: China
facility: Anhui Provincial Cancer Hospital
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical University
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Chongqi
country: China
facility: The First Affiliated Hospital, Chongqing Medical University
city: Dalian
country: China
facility: The Second Hospital of Dalian Medical University
city: Deyang
country: China
facility: Deyang People's Hospital
city: Fuyang
country: China
facility: Fuyang Cancer Hosptial
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
city: Guandong
country: China
facility: Zhujiang Hospital of Nanfang Medical University
city: Guangdong
country: China
facility: Guangdong Provincial People's Hospital
city: Guangdong
country: China
facility: Meizhou People's Hospital
city: Guangdong
country: China
facility: Peking University Shenzhen Hospital
city: Guangdong
country: China
facility: Sun Yat-Sen University- Cancer Center
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
city: Hangzhou
country: China
facility: The First Affiliated Hospital, College of Medicine, Zhejiang University
city: Hangzhou
country: China
facility: Zhejiang Provincial Hospital of Chinese Medicine
city: Hebei
country: China
facility: Hebei Medical University - The Fourth Hospital - Hebei Provincial Tumor Hospital
city: Hubei
country: China
facility: Xiangyang Central Hospital
city: Hunan
country: China
facility: Xiangya Hospital Central South University
city: Jinan
country: China
facility: Shandong Province Tumor Hospital
city: Lanzhou
country: China
facility: Gansu Provincial Hospital
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
city: Linyi
country: China
facility: Linyi Cancer Hospital
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
city: Luzhou
country: China
facility: The Affiliated Hospital of Southwest Medical University (Luzhou Medical College)
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
city: Nanchang
country: China
facility: Nangchang People's Hospital
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
city: Nanning
country: China
facility: Guangxi Medical University Cancer Hospital
city: Nanyang
country: China
facility: Nanyang Central Hospital
city: Neijiang
country: China
facility: The Second People's Hospital of Neijiang
city: Ningbo
country: China
facility: Ningbo Medical Center Li Huili Hospital
city: Qingdao
country: China
facility: Qingdao Central Hospital, University of Health and Rehabilitation Sciences
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
city: Shang'ai
country: China
facility: Fudan University Cancer Center
city: Shanxi
country: China
facility: First Affiliated Hospital of Xi'an Jiaotong University
city: Shaoyang
country: China
facility: The Central Hospital of Shaoyang
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Institute
city: Shouguang
country: China
facility: Yuebei People's Hospital
city: Sichuan
country: China
facility: University of Electonic Science & Technology (UESTC) - Sichuan Cancer Hospital & Institute
city: Tianjin
country: China
facility: Tianjin Cancer Hospital Airport Hospital
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
city: Wuhan
country: China
facility: Hubei Cancer Hospital
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technolog
city: XI Ail
country: China
facility: The First Affiliated Hospital of Air Force Medical University
city: Xiamen
country: China
facility: The first affiliated hospital of Xiamen University
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
city: Yuncheng
country: China
facility: Yuncheng Central Hospital
city: Zhejiang
country: China
facility: Zhejiang cancer hospital
city: Zhejiang
country: China
facility: Zhejiang Provincial People's Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
city: Zhongshan
country: China
facility: Zhongshan City People's Hospital
city: Zhumadian
country: China
facility: Zhumadian Central Hospital
city: Ürümqi
country: China
facility: The Affiliated Cancer Hospital of Xinjiang Medical University
city: Besançon
country: France
facility: Service d'Oncologie Medicale - CHRU Besancon
city: Bordeaux
country: France
facility: Institut Bergonie
city: CAEN Cedex 05
country: France
facility: Centre Francois Baclesse
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Poitiers
country: France
facility: CHU Poitiers - Pole Regional de Cancerologie de Poitiers (PRC)
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus Dresden
city: München
country: Germany
facility: Klinikum rechts der Isar der Technischen Universitaet Muenchen
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Hadassah Ein-Karem Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Petach Tikva
country: Israel
facility: Rabin MC
city: Reẖovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Tel HaShomer
country: Israel
facility: Sheba Medical Center
city: Aviano
country: Italy
facility: Centro Riferimento Oncologico - Aviano
city: Meldola
country: Italy
facility: IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST S.r.l.
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Misterbianco
country: Italy
facility: Humanitas Istituto Clinico Catanese
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona-Ospedale Borgo Trento
city: Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Biała Podlaska
country: Poland
facility: KO - MED Centra Kliniczne Sp. z o.o., Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach, I Klinika Radioterapii i Chemioterapii
city: Krakow
country: Poland
facility: Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie - Oddzial Onkologii Klinicznej z Pododdzialem Dziennym
city: Kraków
country: Poland
facility: SP ZOZ Szpital Uniwersytecki w Krakowie, Oddzial Onkologii Klinicznej
city: Poznań
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Poznaniu, Oddzial Chemioterapii
city: Poznań
country: Poland
facility: Wielkopolskie Centrum Onkologii (WCO) / The Greater Poland Cancer Center
city: Wieliszew
country: Poland
facility: Mazowiecki Szpital Onkologiczny
city: Łódź
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki - Klinika Onkologii
city: Bucharest
country: Romania
facility: Centrul Medical Focus
city: Bucharest
country: Romania
facility: Filantropia Clinical Hospital
city: Cluj-Napoca
country: Romania
facility: Radiotherapy Center Cluj
city: Craiova
country: Romania
facility: Onco Clinic Consult SA
city: Craiova
country: Romania
facility: Oncology Center Sfantul Nectarie
city: Piteşti
country: Romania
facility: Gral Medical SRL
city: Timişoara
country: Romania
facility: OncoMed Oncology Center
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Singapore
country: Singapore
facility: Curie Oncology
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra - Madrid
city: Madrid
country: Spain
facility: Hospital Beata Maria Ana
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital (CCH)
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: Tri-Service General Hospital
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital (CGMHLK)
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: London
country: United Kingdom
facility: Charing Cross Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
Study officials:
References: