Study of Abemaciclib and Elacestrant in Participants With Brain Metastasis Due to ER+/HER-2- Breast Cancer

NCT05386108 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: ELA-01212024-512878-98-00
• Study Type: interventional
• Target: 73
• Locations: 10 countries
• Sites: 86

Brief Summary

This is a multi-site, global, open-label study that includes a phase 1b evaluation of elacestrant in combination with abemaciclib in women and men with brain metastases from estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER-2) negative breast cancer. Phase 1b was designed to select the recommended phase 2 dose (RP2D) and is followed by an ongoing phase 2 evaluation of elacestrant in combination with abemaciclib in participants with active brain metastases from ER-positive, HER-2 negative breast cancer.

Conditions

Central Nervous System Diseases; Breast Neoplasms; Brain Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Central Nervous System Neoplasms; Brain Diseases

Outcome Measures

Primary Outcomes (2)

• Phase 1b: RP2D

  Based on the observed number of dose-limiting toxicities (DLTs) during the first cycle. Dose-limiting toxicity is based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. DLTs will be evaluated during the first cycle (28 days) of treatment in up to 3 cohorts during Phase 1b. A DLT will be defined as any of the toxicities listed in the protocol that are not clearly due to breast cancer or extraneous causes.

  Cycle 1 (28 days)

• Phase 2: Objective Response Rate (ORR) Per Overall Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1)

  Defined as the proportion of participants with a best overall response (BOR) of either a confirmed complete response (CR) or partial response (PR) per blinded independent central review (BICR).

  3 years

Secondary Outcomes (29)

• Phase 1b and 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  3 years

• Phase 1b and 2: Area Under the Concentration-time Curve Over the Dosing Interval (AUC0-tau)

  Cycle 1 Day 15 (predose and up to 24 hours postdose) (Cycle length = 28 days)

• Phase 1b and 2: Maximum Observed Plasma Concentration (Cmax)

  Cycle 1 Day 15 (predose and up to 24 hours postdose) (Cycle length = 28 days)

• Phase 1b and 2: Time to Reach Cmax (Tmax)

  Cycle 1 Day 15 (predose and up to 24 hours postdose) (Cycle length = 28 days)

• Phase 1b: ORR As Per Local Investigator's Assessment and Per BICR

  3 years

Study Arms (4)

Phase 1b Cohort 1

EXPERIMENTAL

Elacestrant 300 milligrams (mg) once daily (QD) + abemaciclib 100 mg twice daily (BID)

Drug: Elacestrant; Drug: Abemaciclib

Phase 1b Cohort 2

EXPERIMENTAL

Elacestrant 400 mg QD + abemaciclib 100 mg BID

Drug: Elacestrant; Drug: Abemaciclib

Phase 1b Cohort 3

EXPERIMENTAL

Elacestrant 400 mg QD + abemaciclib 150 mg BID

Drug: Elacestrant; Drug: Abemaciclib

Phase 2

EXPERIMENTAL

Elacestrant in combination with abemaciclib at the RP2D determined in Phase 1b

Drug: Elacestrant; Drug: Abemaciclib

Interventions

Elacestrant DRUG

300 mg, 400 mg

Also known as: Elacestrant dihydrochloride, RAD-1901, ER-306323, Orserdu

Phase 1b Cohort 1; Phase 1b Cohort 2; Phase 1b Cohort 3; Phase 2

Abemaciclib DRUG

100 mg, 150 mg

Also known as: Verzenio

Phase 1b Cohort 1; Phase 1b Cohort 2; Phase 1b Cohort 3; Phase 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has the signed informed consent form before any study-related activities according to local guidelines.
• Women or men aged ≥18 years, at the time of informed consent signature.
• Female participants may be either postmenopausal or pre/perimenopausal. Postmenopausal status is defined by:
• Age ≥60 years
• Age \<60 years and amenorrhea for 12 or more months without an alternative cause) and follicle stimulating hormone and estradiol in postmenopausal ranges per local reference ranges
• Documentation of prior bilateral oophorectomy, at least 1 month before first dose of trial therapy).
• Pre-menopausal / peri-menopausal women and men must be concurrently receiving a luteinizing hormone-releasing hormone (LHRH) agonist starting at least 3-4 weeks before the start of trial therapy and is planning to continue LHRH during the study.
• Participant must have ER-positive, HER-2 negative tumor status as confirmed by local laboratory testing in the following manner:
• Documentation of ER positive tumor with ≥ 1% staining by immunohistochemistry (IHC) as defined in the 2010 or 2020 American Society for Clinical Oncology (ASCO) recommendations for ER testing, with or without progesterone receptor (PGR) positivity
• HER-2 negative tumor with an IHC result of 0 or 1+ for cellular membrane protein expression or an in situ hybridization negative result as defined in the 2013 or 2018 ASCO recommendations for HER-2 testing
• In Phase 2, participants must have at least one active and measurable brain metastasis per RECIST version 1.1.
• Any of the following qualifies brain metastases as active:
• Newly diagnosed brain metastasis in participants who never received prior central nervous system (CNS)-directed therapy.
• Newly diagnosed brain metastasis outside any area that was previously subjected to CNS-directed therapy.
• Brain metastases demonstrating unequivocal progression in the opinion of the treating investigator in an area that has previously been subjected to CNS-directed therapy.

You may not qualify if:

• Immediate CNS-specific treatment is likely to be required, per the treating physician's assessment.
• Participant has imminent organ failure and/or visceral crisis.
• Participant has leptomeningeal metastases, defined as having positive cerebrospinal fluid (CSF) cytology or unequivocal radiologic and clinical evidence of leptomeningeal involvement. Note: Discrete dural metastases are permitted.
• Breast cancer treatment-naïve participants (that is, not having received any systemic therapy) in the advanced/metastatic setting.
• History of pulmonary embolism (PE), cardiovascular accident (CVA), myocardial infarction (MI) in the past 6 months from screening visit.
• Prior therapy with abemaciclib in the metastatic setting. Note: Use of abemaciclib in the adjuvant setting is allowed if the last treatment administration was more than 12 months prior to first recurrence.
• Prior therapy with elacestrant or other investigational selective estrogen receptor degraders (SERDs), or investigational alike agents such as selective estrogen receptor modulators (SERMs), selective estrogen receptor covalent antagonists (SERCANs), complete estrogen receptor antagonists (CERANs), and proteolysistargeting chimeras (PROTACs) in the metastatic setting.
• Participant has a concurrent malignancy or malignancy within 3 years of enrollment, with the exception of adequately treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or second primary breast cancer; and any other malignancy that is considered in complete remission by the Investigator(s) that is approved by the Medical Monitor.
• Currently participating in another breast cancer intervention clinical study. Participants who are being followed for overall survival for another clinical trial with no therapy and study intervention are allowed after the washout period for any prior therapy.
• Prior anti-cancer or investigational drug treatment within the following windows:
• Fulvestrant treatment (last injection) \<42 days before first dose of study drug
• Any other endocrine therapy \<14 days before first dose of study drug. Note: LHRH agonists should not be counted as endocrine therapy.
• Chemotherapy or other anti-cancer therapy \<14 days before first dose of study drug
• Any investigational anti-cancer drug therapy within \<28 days or \<5 half lives, whichever is shorter
• Bisphosphonates or receptor activator of nuclear factor-κB ligand (RANKL) inhibitors initiated, or dose changed \<1 month prior to first dose of study drug according to institutional guidelines.

Sponsors & Collaborators

• Stemline Therapeutics, Inc.: lead

Study Sites (86)

Providence Medical Foundation

Fullerton, California, 92835, United States

RECRUITING

California Research Institute

Los Angeles, California, 90027, United States

RECRUITING

Carle Cancer Center

Urbana, Illinois, 61801, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Henry Ford Hospital

Detroit, Michigan, 48202, United States

RECRUITING

Miami Valley Hospital South

Centerville, Ohio, 45459, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, 97239, United States

COMPLETED

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

UT Health San Antonio University of Texas

San Antonio, Texas, 78229, United States

COMPLETED

Virginia Cancer Institute

Norfolk, Virginia, 00115, United States

RECRUITING

Antwerp University Hospital

Edegem, 2650, Belgium

RECRUITING

Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg

Leuven, Belgium

RECRUITING

Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc

Woluwe-Saint-Lambert, Belgium

RECRUITING

Institut de Cancerologie de l'Ouest site Paul Papin

Angers, France

RECRUITING

Hôpital Morvan - CHRU de Brest - cancérologie et d'hématologie

Brest, France

RECRUITING

Centre Francois Baclesse - Oncologie Medicale - Cancerolo

Caen, France

RECRUITING

Centre Jean Perrin

Clermont-Ferrand, France

RECRUITING

Centre Léon Bérard - Département Oncologie Médicale

Lyon, France

RECRUITING

Centre de Cancerologie du Grand Montpellier

Montpellier, 37070, France

RECRUITING

Hôpital de la Pitiê Salpêtriêre

Paris, 75103, France

RECRUITING

Centre Hospitalier Universitaire de Poitiers

Poitiers, 86000, France

RECRUITING

Institut Claudius Regaud

Toulouse, 31100, France

RECRUITING

Klinikum Bayreuth GmbH

Bayreuth, 95445, Germany

RECRUITING

Uniklinik Koeln - Klinik und Poliklinik fuer Frauenheilkunde

Cologne, Germany

COMPLETED

Universitatsklinikum Carl Gustav Carus

Dresden, Germany

RECRUITING

Universitaetsklinikum Duesseldorf

Düsseldorf, Germany

RECRUITING

Universitätsklinikum Erlangen

Erlangen, Germany

RECRUITING

Medizinische Hochschule Hannover

Hanover, Germany

RECRUITING

Universitätsklinikum Leipzig

Leipzig, Germany

RECRUITING

Klinikum Worms gGmbH

Worms, 67550, Germany

RECRUITING

Helios Klinikum Wuppertal

Wuppertal, Germany

RECRUITING

National and Capodistrian University of Athens - University General Hospital Attikon

Athens, 12462, Greece

RECRUITING

Metropolitan Hospital [Oncology]

Piraeus, 12462, Greece

RECRUITING

EUROMEDICA General Clinic of Thessaloniki

Thessaloniki, 54645, Greece

COMPLETED

Interbalkan European Medical Center

Thessaloniki, 57001, Greece

RECRUITING

AOU Ospedali Riuniti Umberto I-G.M.Lancisi -G.Salesi

Ancona, Italy

RECRUITING

Istituto di Candiolo, IRCCS

Candiolo, Italy

RECRUITING

Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST IRCCS

Meldola, Italy

RECRUITING

A. O. Ospedali Riuniti Parpardo, Piemonte, Messina

Messina, Italy

RECRUITING

IEO - Istituto Europeo di Oncologia, IRCCS

Milan, Italy

RECRUITING

Azienda Ospedaliero-Universitaria di Modena, Policlinico di Modena

Modena, Italy

RECRUITING

Ospedale San Gerardo, ASST di Monza, IRCCS

Monza, Italy

RECRUITING

Azienda Ospedaliera Universitaria Federico II

Naples, Italy

RECRUITING

Istituto Nazionale dei Tumori - Fondazione Pascale, IRCCS

Naples, Italy

RECRUITING

Istituto Oncologico Veneto IOV - IRCCS

Padua, Italy

RECRUITING

IRCCS Policlinico San Matteo, Università degli studi di Pavia, Pavia Fondazione IRCCS Policlinico San Matteo

Pavia, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, Italy

RECRUITING

Azienda Ospedaliera Santa Maria di Terni

Terni, Italy

RECRUITING

AOU Città della Salute e della Scienza di Torino, Ospedale Molinette

Torino, Italy

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Gangnam Severance Hospital

Seoul, 06273, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Ewha Womans University MokDong Hospital

Seoul, 07985, South Korea

RECRUITING

Seoul National University Bundang Hospital

Seoul, South Korea

RECRUITING

Seoul National University Hospital

Seoul, South Korea

RECRUITING

University Hospital Reina Sofía

Córdoba, Andalusia, 14004, Spain

RECRUITING

University Hospital Ramón y Cajal

Madrid, Madrid, 28034, Spain

RECRUITING

University Hospital 12 de Octubre

Madrid, Madrid, 28041, Spain

RECRUITING

Clara Campal Comprehensive Cancer Center (CIOCC)

Madrid, Madrid, 28050, Spain

RECRUITING

University Clinical Hospital Virgen de la Arrixaca

El Palmar, Murcia, 30120, Spain

RECRUITING

Hospital Clinic De Barcelona

Barcelona, 08036, Spain

RECRUITING

Hospital Universitari Vall D Hebron

Barcelona, Spain

RECRUITING

Clinica Universidad de Navarra

Madrid, Spain

RECRUITING

Hospital Clínico San Carlos

Madrid, Spain

RECRUITING

Hospital Universitario Quirónsalud Madrid

Madrid, Spain

RECRUITING

Clinica Universidad de Navarra

Pamplona, Spain

RECRUITING

Complexo Hospitalario Universitario De Santiago

Santiago de Compostela, 15706, Spain

RECRUITING

Fundación Instituto Valenciano De Oncología

Valencia, Spain

RECRUITING

Hospital Universitario Virgen del Rocío

Valencia, Spain

RECRUITING

Adana Sehir Hastanesi

Adana, Turkey (Türkiye)

RECRUITING

Ankara Bilkent Sehir Hastanesi Tibbi Onkoloji Klinigi

Ankara, Turkey (Türkiye)

RECRUITING

Ankara University Medical Faculty

Ankara, Turkey (Türkiye)

RECRUITING

Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi

Ankara, Turkey (Türkiye)

RECRUITING

Gulhane Egitim ve Arastirma Hastanesi Tibbi Onkoloji Klinigi

Ankara, Turkey (Türkiye)

RECRUITING

Hacettepe University Medical Faculty

Ankara, Turkey (Türkiye)

RECRUITING

Memorial Ankara Hastanesi Tibbi Onkoloji

Ankara, Turkey (Türkiye)

RECRUITING

Ege University Medical Faculty

Bornova, Turkey (Türkiye)

RECRUITING

Acibadem Altunizade Hospital

Istanbul, Turkey (Türkiye)

RECRUITING

Medipol Mega Hospital - Medical Oncology

Istanbul, Turkey (Türkiye)

RECRUITING

Prof. Dr. Suleyman Yalcin Sehir Hastanesi

Istanbul, Turkey (Türkiye)

RECRUITING

University Hospitals of Leicester NHS Trust -Glenfield Hospital

Leicester, United Kingdom

WITHDRAWN

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, United Kingdom

WITHDRAWN

Guy's and St Thomas' NHS Foundation Trust

London, United Kingdom

RECRUITING

University College London Hospitals NHS Foundation Trust - University College Hospital (UCH) - Macmillan Cancer Centre

London, United Kingdom

RECRUITING

The Christie NHS Foundation Trust - Medical Oncology

Manchester, M20 4BX, United Kingdom

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Central Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases

Interventions

elacestrant; RAD1901; abemaciclib

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Nervous System Neoplasms; Nervous System Diseases

Central Study Contacts

Stemline Trials

CONTACT

1-877-332-7961; clinicaltrials@menarinistemline.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2022
• First Posted: May 23, 2022
• Study Start: August 31, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (14); FR (9); GR (4); TU (11); US (11); DE (9); GB (5); IT (14); KR (6); BE (3)