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

Recruiting now · Phase 1/Phase 2

Conditions studied: Breast Neoplasms, Brain Neoplasms, Neoplasms by Site, Neoplasms, Breast Diseases, Central Nervous System Neoplasms, Brain Diseases, Central Nervous System Diseases

In brief

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.

Key facts

Study ID

NCT05386108

Run by

Stemline Therapeutics, Inc.

People needed

73

Starts

2022-08-31

Expected to finish

2026-12-01

Last updated by the study team

2026-08-06

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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.
• For lesions, including brain metastases, to qualify as measurable, and possibly be selected as target lesions, per RECIST version 1.1, the longest diameter must be ≥10 millimeters [mm] by computed tomography [CT] or magnetic resonance imaging [MRI]).
• In Phase 1b, the presence of brain metastases is allowed but not required for eligibility, in this case, at least 1 measurable lesion outside the brain is required.
• Participants receiving concomitant corticosteroids must be on a stable or decreasing dose for at least 7 days prior to baseline and not receiving doses higher than 4 mg of dexamethasone per day or equivalent.
• Participants have experienced no more than one seizure within 4 weeks prior to starting trial therapy.
• Participants' prior therapy received in the metastatic setting includes:
• At least one endocrine therapy
• Up to two chemotherapy regimens
• Up to two lines of prior cyclin-dependent kinase (CDK) 4/6 inhibitor, not including abemaciclib
• Note 1: Toxicity from prior therapy must be resolved to NCI CTCAE version 5.0 Grade ≤1, with the exception of alopecia and peripheral sensory neuropathy (Grade ≤2).
• Note 2: Chemotherapy refers to not targeted cytotoxic agents (for example, alkylating agents, taxanes, nucleotide analogs, platinum-based drugs, vinca alkaloids, etc) and antibody drug conjugates (ADCs). Targeted therapies (for example, kinase inhibitors) are not considered chemotherapy for eligibility purposes. Not targeted cytotoxic agents administered for less than 1 cycle will not be counted as a prior chemotherapy regimen.

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.
• Radiation therapy (including CNS directed) within 7 days before the first dose of study drug or without a full recovery from radiotherapy acute effects.
• Uncontrolled significant active infections
• Participants with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection must have undetectable viral load (or detected below the lower limit of quantification) during screening
• Participants known to be human immunodeficiency virus positive (HIV+) are allowed as long as they have undetectable viral load (viral suppression) at baseline.
• Major surgery within 4 weeks of starting trial therapy.
• Inability to take oral medication, or history of malabsorption syndrome or any other uncontrolled gastrointestinal condition that may significantly alter the absorption of study drugs.
• Females of childbearing potential who do not agree to use a highly effective non-hormonal method of contraception and to abstain from donating ova within 28 days of the first dose of study treatment through 120 days after the last dose of study treatment. Highly effective non-hormonal method of contraception includes any of the following:
• Intrauterine device (non-hormonal)
• Sexual abstinence
• Bilateral tubal occlusion/ligation

Where it is running

• Universitatsklinikum Carl Gustav Carus — Dresden, Germany (enrolling)
• Universitaetsklinikum Duesseldorf — Düsseldorf, Germany (enrolling)
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (enrolling)
• California Research Institute — Los Angeles, California, United States (enrolling)
• Providence Medical Foundation — Fullerton, California, United States (enrolling)
• Carle Cancer Center — Urbana, Illinois, United States (enrolling)
• SCRI Oncology Partners — Nashville, Tennessee, United States (enrolling)
• University of Texas MD Anderson Cancer Center — Houston, Texas, United States (enrolling)
• Henry Ford Hospital — Detroit, Michigan, United States (enrolling)
• Virginia Cancer Institute — Norfolk, Virginia, United States (enrolling)
• Miami Valley Hospital South — Centerville, Ohio, United States (enrolling)
• Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg — Leuven, Belgium (enrolling)
• Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc — Woluwe-Saint-Lambert, Belgium (enrolling)
• Institut de Cancerologie de l'Ouest site Paul Papin — Angers, France (enrolling)
• Hôpital Morvan - CHRU de Brest - cancérologie et d'hématologie — Brest, France (enrolling)
• Centre Francois Baclesse - Oncologie Medicale - Cancerolo — Caen, France (enrolling)
• Centre Jean Perrin — Clermont-Ferrand, France (enrolling)
• Centre Léon Bérard - Département Oncologie Médicale — Lyon, France (enrolling)
• Centre de Cancerologie du Grand Montpellier — Montpellier, France (enrolling)
• Hôpital de la Pitiê Salpêtriêre — Paris, France (enrolling)
• Centre Hospitalier Universitaire de Poitiers — Poitiers, France (enrolling)
• Institut Claudius Regaud — Toulouse, France (enrolling)
• Klinikum Bayreuth GmbH — Bayreuth, Germany (enrolling)
• Antwerp University Hospital — Edegem, Belgium (enrolling)
• Universitätsklinikum Erlangen — Erlangen, Germany (enrolling)

Full record on ClinicalTrials.gov

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