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

Metastatic Breast Cancer Clinical Trial

— ELAINEIII  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05696626
• Other study ID #: SMX 22-002
• Status: Recruiting
• Phase: Phase 3
• Start date: October 31, 2023
• Est. completion date: June 2026

Study information

• Verified date: June 2024
• Source: Sermonix Pharmaceuticals Inc.
• Contact: Sermonix Pharmaceuticals Study Inquiry
• Phone: 614-864-4919
• Email: info[@]sermonixpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: June 2026
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Lasofoxifene in combination with abemaciclib
5 mg/d of oral lasofoxifene plus oral abemaciclib 150 mg twice a day
• 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

Locations

Country	Name	City	State
Australia	Blacktown Hospital	Blacktown
Australia	Concord Repatriation General Hospital	Concord
Australia	Mater Misericordiae Ltd, South Brisbane	South Brisbane
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Antwerp University Hospital (UZA)	Edegem
Belgium	Universitaire Ziekenhuizen Leuven	Leuven
Belgium	Clinique CHC MontLégia	Liège
Belgium	CHU UCL Namur - Site De Sainte-Elisabeth	Namur
Canada	Hospital Maisonneuve-Rosemont	Montréal	Quebec
Canada	Lady Davis Institute for Medical Research Jewish General Hospital	Montréal	Quebec
Canada	The Ottawa General Hospital	Ottawa	Ontario
Canada	Sunnybrook Health Sciences Centre -Bayview Campus	Toronto	Ontario
Czechia	Masarykuv onkologicky ustav	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Králové
Czechia	Fakultni nemocnice Olomouc - Oncology clinic	Olomouc
Czechia	Fakultní nemocnice v Motole	Praha 5
France	Service d'Oncologie Medicale - CHRU Besancon	Besançon
France	Institut Bergonie	Bordeaux
France	Centre Francois Baclesse	CAEN Cedex 05
France	Centre Oscar Lambret	Lille
France	Centre Leon Berard	Lyon
France	Institut Paoli-Calmettes	Marseille
France	CHU Poitiers - Pole Regional de Cancerologie de Poitiers (PRC)	Poitiers
France	Centre Henri Becquerel	Rouen
France	Institut de cancerologie Strasbourg Europe (ICANS)	Strasbourg
France	Institut Claudius Regaud	Toulouse
Germany	Universitaetsklinikum Carl Gustav Carus Dresden	Dresden
Germany	Universitaetsklinikum Ulm	Ulm
Hungary	Budapesti Uzsoki Utcai Korhaz	Budapest
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah Ein-Karem Medical Center	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Rabin MC	Petach Tikva
Israel	Kaplan Medical Center	Re?ovot
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Israel	Sheba Medical Center	Tel HaShomer
Italy	Centro Riferimento Oncologico - Aviano	Aviano
Italy	IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST S.r.l.	Meldola
Italy	Istituto Europeo di Oncologia	Milano
Italy	Humanitas Istituto Clinico Catanese	Misterbianco
Italy	Azienda Ospedaliero-Universitaria di Modena	Modena
Italy	Istituto Nazionale Tumori IRCCS Fondazione G. Pascale	Napoli
Italy	Azienda Ospedaliero Universitaria di Parma	Parma
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore	Roma
Italy	Azienda Ospedaliera Universitaria Integrata Verona-Ospedale Borgo Trento	Verona
Korea, Republic of	National Cancer Center	Gyeonggi-do
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Poland	KO - MED Centra Kliniczne Sp. z o.o., Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej	Biala Podlaska
Poland	Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii	Gdansk
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach, I Klinika Radioterapii i Chemioterapii	Gliwice
Poland	Swietokrzyskie Centrum Onkologii Samodzielny Publiczny Zaklad Opieki Zdrowotnej, Klinika Onkologii Klinicznej	Kielce
Poland	Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie - Oddzial Onkologii Klinicznej z Pododdzialem Dziennym	Krakow
Poland	SP ZOZ Szpital Uniwersytecki w Krakowie, Oddzial Onkologii Klinicznej	Kraków
Poland	Instytut Centrum Zdrowia Matki Polki - Klinika Onkologii	Lódz
Poland	NeuroMed	Lublin
Poland	Wielkopolskie Centrum Onkologii (WCO) / The Greater Poland Cancer Center	Poznan
Poland	Mazowiecki Szpital Onkologiczny	Wieliszew
Romania	Centrul Medical Focus	Bucharest
Romania	Filantropia Clinical Hospital	Bucharest
Romania	Radiotherapy Center Cluj	Cluj-Napoca
Romania	Onco Clinic Consult SA	Craiova
Romania	Oncology Center Sfantul Nectarie	Craiova
Romania	Gral Medical SRL	Pitesti
Romania	OncoMed Oncology Center	Timisoara
Singapore	Curie Oncology	Singapore
Singapore	National Cancer Centre Singapore	Singapore
Spain	Hospital Clinic Barcelona	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario Reina Sofia	Córdoba
Spain	Clinica Universidad de Navarra - Madrid	Madrid
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario de La Princesa	Madrid
Spain	Hospital Regional Universitario de Malaga	Málaga
Spain	Clinica Universidad de Navarra - Pamplona	Pamplona
Spain	Instituto Valenciano de Oncologia	Valencia
Taiwan	Changhua Christian Hospital (CCH)	Changhua
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)	Kaohsiung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei City
Taiwan	Linkou Chang Gung Memorial Hospital (CGMHLK)	Taoyuan City
Turkey	Ankara University Medical Faculty Medical Oncology Department	Ankara
Turkey	Uludag University Medical Faculty	Bursa
Turkey	Liv Hospital Ankara	Cankaya
Turkey	Goztepe Prof. Dr. Suleyman Yalcin City Hospital	Istanbul
Turkey	Medical Point Izmir Hospital	Izmir
Turkey	Suat Seren Training and Research Hospital	Izmir
Turkey	Kocaeli University Faculty of Medicine	Izmit	Kocaeli
Turkey	Trakya University Medical Faculty	Merkez	Edirne
United Kingdom	West Middlesex University Hospital	Isleworth
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	Lancashire Teaching Hospitals	Preston
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Johns Hopkins Kimmel Cancer Center	Baltimore	Maryland
United States	Hematology Oncology Clinic	Baton Rouge	Louisiana
United States	New Jersey Cancer Care, PA	Belleville	New Jersey
United States	Boca Raton Regional Hospital	Boca Raton	Florida
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Vermont Medical Center	Burlington	Vermont
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	Duke University Medical Center	Durham	North Carolina
United States	Altru Health Systems	Grand Forks	North Dakota
United States	Cancer and Hematology Centers of Western Michigan	Grand Rapids	Michigan
United States	Baylor College of Medicine	Houston	Texas
United States	Harris Health System - Smith Clinic	Houston	Texas
United States	Lyndon B. Johnson Hospital	Houston	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Saint Luke's Cancer Institute	Kansas City	Missouri
United States	California Research Institute	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Miami Cancer Institute	Miami	Florida
United States	Allina Health System DBA Virginia Piper Cancer Institute	Minneapolis	Minnesota
United States	David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Oklahoma University Health Sciences Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Mayo Clinic - Phoenix	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Miami Cancer Institute Plantation	Plantation	Florida
United States	Renown Regional Medical Centre	Reno	Nevada
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Providence Medical Foundation - Santa Rosa, CA	Santa Rosa	California
United States	University of Arizona - Cancer Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Sermonix Pharmaceuticals Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  Poland,  Romania,  Singapore,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival (PFS)	PFS is defined as the time from the date of randomization [Visit 0 (Day 1)] to the earliest date of first documented progression per RECIST 1.1 or death due to any cause.	Within approximately 3 years
Secondary	Objective response rate (ORR)	ORR is defined as the percentage of subjects with measurable disease at baseline whose best overall response is either a confirmed CR or a confirmed PR according to RECIST 1.1.	Within approximately 3 years
Secondary	Overall survival (OS)	Overall survival is defined as time from the date of Visit 0 (Day 1) to death due to any cause.	Within approximately 3 years
Secondary	Clinical benefit rate (CBR)	CBR is defined as the percentage of subjects with best overall response of confirmed CR, confirmed PR, or stable disease (SD) with a duration of 24 weeks or longer according to RECIST 1.1. As used in this calculation, stable disease is defined as stable disease in those subjects with measurable disease plus nonPR/non progressive disease (PD) in subjects with non-measurable disease.	Within approximately 3 years
Secondary	Duration of response (DoR) in subjects with an objective response	DoR is from the date of first documented confirmed response (CR or PR) to the date of first documented progression of disease or death due to any cause, whichever is earlier.	Within approximately 3 years
Secondary	Time to response (TTR) in subjects with an objective response	TTR is from the date of randomization to the date of first documented confirmed response (CR or PR).	Within approximately 3 years
Secondary	Time to cytotoxic chemotherapy	From the date of randomization to the date of first documented use of cytotoxic chemotherapy.	Within approximately 3 years
Secondary	Quality of Life (QoL) evaluated using the Functional Assessment of Cancer Therapy-Breast Cancer-Endocrine Subscale (FACT B-ES)	Scale ranges from 'Not at all' to 'Very much'	Within approximately 3 years
Secondary	Incidence of Adverse Events (AEs) and Serious AEs	The type, severity (graded by Common Terminology Criteria for Adverse Events [CTCAE version 5.0]), course, duration, seriousness, and relationship to study treatment will be assessed at each visit	Within approximately 3 years