Open-Label Umbrella Study To Evaluate Safety And Efficacy Of Elacestrant In Various Combination In Participants With Metastatic Breast Cancer (ELEVATE)

A Phase 1b/2, Open-Label Umbrella Study To Evaluate Safety And Efficacy Of Elacestrant In Various Combination In Patients With Metastatic Breast Cancer

This is a multicenter, Phase 1b/2 trial in participants with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced/metastatic breast cancer. The phase 1b part of the trial will determine the recommended Phase 2 dose (RP2D) of elacestrant when administered in combination with alpelisib, everolimus, palbociclib, capivasertib, and ribociclib. The Phase 2 part of the trial will evaluate the efficacy and safety of the various combinations.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer; Metastatic Breast Cancer
• Intervention / Treatment: Drug: Elacestrant; Drug: Everolimus; Drug: Ribociclib; Drug: Palbociclib; Drug: Capivasertib; Drug: Abemaciclib; Drug: Alpelisib

Detailed Description

This is a multicenter, Phase 1b/2 trial. The Phase 1b aims at selecting the RP2D dose, defined as a dose that is associated with less than 33% of participants experiencing a dose-limiting toxicity (DLT) of elacestrant when administered in combination with alpelisib, everolimus, palbociclib, ribociclib, and capivasertib that is, ≤1 participant experiencing a DLT out of 6 DLT-evaluable participants. For each combination, this phase will have approximately 3 cohorts of up to 6 DLT-evaluable participants each. The total number of DLT-evaluable participants in all the combinations will be up to 125.

The Phase 2 part of the trial will evaluate the efficacy and safety of the various combinations.

The treatment arms will be:

• Arm A: 50 participants: elacestrant with alpelisib;
• Arm B: 50 participants: elacestrant with everolimus;
• Arm C: 60 participants (30 participants in each combination): elacestrant with either abemaciclib or ribociclib;
• Arm D: 90 participants (30 participants in each combination): elacestrant with either palbociclib, abemaciclib, or ribociclib;
• Arm E: 60 participants: elacestrant with capivasertib

Phase 1b will have a total of 125 participants, while Phase 2 will have 310 participants for all treatment arm combinations.

• Study Type: Interventional
• Enrollment (Estimated): 435
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1017AAS
    • Centro Medico Austral
  • Córdoba, Argentina, X5008HHW
    • Cemaic - Centro De Especialidades Medicas Ambulatorias E Investigacion Clinica
  • La Rioja, Argentina, 01122
    • Centro Oncologico Riojano Integral (CORI)
• Australia
  • Sydney, Australia, 2113
    • Macquarie University
• Belgium
  • Anderlecht, Belgium, 01070
    • Institut Jules Bordet
  • Charleroi, Belgium, 06000
    • Grand Hôpital de Charleroi - Site Notre Dame
  • Leuven, Belgium, 03000
    • Universitaire Ziekenhuizen (Uz) Leuven - Campus Gasthuisberg - Multidisciplinair Borstcentrum (Multidisciplinary Breast Center) (Mbc)
• Brazil
  • Goiânia, Brazil, 74605-070
    • ACCG - Hospital Araujo Jorge
  • Itajaí, Brazil, 88301-220
    • Clinica Neoplasias Litoral
  • Porto Alegre, Brazil, 90610-000
    • Hospital São Lucas da PUCRS
  • Porto Alegre, Brazil, 90850-170
    • Centro Gaucho Integrado de Oncologia; Hematologia; Ensino e Pesquisa - Hospital Mae de Deus/AESC
  • São Paulo, Brazil, 01308-050
    • Hospital Sirio-Libanes (HSL) - Centro De Oncologia - Sao Paulo
• France
  • Lyon, France, 69495
    • Centre Hospitalier Lyon SUD- HCL
  • Montpellier, France, 34070
    • Centre de Cancérologie du Grand Montpellier
  • Rouen, France, 76038 Cedex 1
    • Centre de Cancérologie du Grand Montpellier
  • Toulouse, France, 31059 Cedex 09
    • Centre Hospitalier Universitaire (Chu) De Toulouse - Institut Universitaire Du Cancer De Toulouse-Oncopole (Iuct-Oncopole) (Institut Claudius Regaud)
  • Villejuif, France, 94805
    • Institut Gustave-Roussy-Umr 981
• Israel
  • Ashdod, Israel, 7747629
    • Samson Assuta Ashdod University Hospital - The Institute of Oncology
  • Haifa, Israel, 352408
    • Rambam Heath
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center
  • Petah Tikva, Israel, 49100
    • Davidoff Rabin Medical Center
  • Ramat Gan, Israel, 5265601
    • Sheba Medical Center; Center Israel
• Italy
  • Brescia, Italy, 25123
    • ASST degli Spedali Civili di Brescia
  • Milan, Italy, 20141
    • Istituto Europeo di Oncologia (IEO)
  • Naples, Italy, 80131
    • Istituto Nazionale Tumori "Fondazione PASCALE"
  • Rimini, Italy, 47923
    • Ospedale Infermi di Rimini - Azienda Unita Sanitaria Locale Della Romagna
• Luxembourg
  • Libramont, Luxembourg, 06800
    • Centre Hospitalier De L'Ardenne
• South Korea
  • Seongnam-si, South Korea, 13620
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 06273
    • Gangnam Severance Hospital
• Spain
  • A Coruña, Spain, 15006
    • Complejo Hospitalario Universitario A Coruña
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08036
    • Hospital Clinic Barcelona
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28007
    • IOB Madrd Institute of Oncology Hospital Beata Maria Ana de Jesus
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Pozuelo de Alarcón, Spain, 28223
    • NEXT Madrid
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Valencia, Spain, 46015
    • Hospital Arnau De Vilanova
  • Valencia, Spain, 46009
    • Fundacion Instituto Valeciano De Oncologia
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 0*6200
    • Abdurrahman Yurtaslan Oncology Hospital
• United Kingdom
  • Liverpool, United Kingdom, L7 8YA
    • The Clatterbridge Cancer Centre NHS Foundation Trust
  • London, United Kingdom, N18 1QX
    • North Middlesex University Hospital
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute UK; Ltd
  • London, United Kingdom, W1T 7HA
    • University College London Hospitals NHS Foundation Trust; The London Clinic - Main Hospital
• United States
  • Alabama
    • Dothan, Alabama, United States, 36303
      • Dothan Hematology and Oncology
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic - Arizona
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology Group
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Los Alamitos, California, United States, 90720
      • OPN Healthcare (Los Alamitos Location)
    • Los Angeles, California, United States, 90048
      • Cedars Sinai
    • Los Angeles, California, United States, 90095
      • UCLA UCLA Hem/Onc - Clinical Research Unit
    • San Francisco, California, United States, 94158
      • UCSF Helen Diller Family Comprehensive Cancer Center
    • Whittier, California, United States, 90603
      • TOI Clinical Research
  • Colorado
    • Lone Tree, Colorado, United States, 80124
      • Rocky Mountain Cancer Centers
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20037
      • George Washington Cancer Center
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Advent Health (Florida Hospital) - Altamonte Springs
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Feinberg Scholl of Medicine Prentice Women's Hospital
  • Kansas
    • Merriam, Kansas, United States, 66204
      • MD Alliance for Multispecialty Research, LLC
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine in St. Louis
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Astera Cancer Care
    • Florham Park, New Jersey, United States, 07932
      • Summit Medical Group
    • New Brunswick, New Jersey, United States, 08901
      • Cooperman Barnabas Medical Center
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • W&IH of RI Breast Health Center of Women and Infants Hospital of Rhode Island
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute / Tennessee Oncology
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor Charles A. Sammons Cancer Center
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center Texas
    • San Antonio, Texas, United States, 78229
      • UT Health San Antonio
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates
  • Washington
    • Spokane Valley, Washington, United States, 99216
      • Cancer Care Northwest
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties (Nwms) - Puyallup - Medical Oncology (Rainier Hematology-Oncology)/Exigent Research Network; LLC
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of WI - Carbone Cancer Center (Phase II only)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant has signed the informed consent before all study specific activities are conducted.

2. Women or men aged ≥18 years (or the minimum age of consent in accordance with the local law), at the time of informed consent signature. Female participants may be of any menopausal status.

   • Postmenopausal status is defined as follows or in accordance with local regulations:

     1. Age ≥60 years or
     2. Age <60 years and amenorrhea for 12 or more months (without an alternative cause) and follicle-stimulating hormone value and an estradiol level within the postmenopausal range per local laboratory reference or
     3. Documentation of bilateral oophorectomy, at least 1 month before first dose of trial therapy.
   • Premenopausal and perimenopausal women (who do not fit postmenopausal criteria) and men must be receiving a luteinizing hormone-releasing hormone (LHRH) agonist and must be initiated at least 3 weeks (4 depending on local label) before the start of trial therapy and are planning to continue LHRH agonist treatment during the study treatment.
3. Histopathological or cytological confirmed ER+, HER2-, breast cancer, per local laboratory, as per the American Society of Clinical Oncology/College of American Pathologists guidelines. Note: In the context of this trial, ER status will be considered positive if ≥10% of tumor cells demonstrate positive nuclear staining by immunohistochemistry, with or without progesterone positivity.
4. Documented radiological disease progression during or after the most recent therapy.
5. At least 1 measurable lesion as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Tumor lesions previously irradiated or subjected to any locoregional treatment will only be considered measurable if there is clear, documented progression at the treated site. For participants with bone only disease, lesions: must be lytic or mixed (lytic + blastic / sclerotic), confirmed and accurately assessed by computed tomography or magnetic resonance imaging, and must have an identifiable soft tissue component meeting the definition of measurability per RECIST v1.1. Note: participants with blastic / sclerotic bone lesions only are not eligible.
6. Eastern Cooperative Oncology Group performance status of 0 or 1.

7. Participant has adequate bone marrow and organ function, as defined by the following laboratory values:

   1. Absolute neutrophil count ≥1.5 × 10^9/liter (L)
   2. Platelets ≥100 × 10^9/L
   3. Hemoglobin ≥9.0 grams/deciliter (g/dL)

   4. Creatinine is ≤ 1.5 x upper limit of normal (ULN) or if creatinine is > 1.5 x ULN, then creatinine clearance must be ≥50 milliliters/minute based on the Cockcroft-Gault formula. Note: C-G formula:

      • Creatinine clearance (male) = ([140-age in years] × weight in kilograms [kg])/ ([serum creatinine in milligrams/deciliter (mg/dL)] × 72)
      • Creatinine clearance (female) = (0.85 × [140-age in years] × weight in kg)/ ([serum creatinine in mg/dL] × 72)

   f. Serum albumin ≥3.0 g/dL (≥30 g/L)

   g. In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × ULN. If the participant has liver metastases, ALT and AST ≤ 5 × ULN

   h. Total serum bilirubin <1.5 × ULN except for participants with Gilbert's syndrome who may be included if the total serum bilirubin is ≤3.0 × ULN or direct bilirubin ≤ 1.5 × ULN.

Additional Criteria for the Alpelisib Combination (Phase 1b and Arm A): In general, the prescription information of the respective combination drug should be consulted for instructions/restrictions with respect to interactions with concomitant medications.

1. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation by local laboratory assessment.
2. One or up to two prior hormonal therapies in the advanced or metastatic setting, one of which was in combination with a cyclin-dependent kinase targeting enzymes CDK4 and CDK6 (CDK4/6) inhibitor.

Additional Criteria for the Everolimus Combination (Phase 1b and Arm B), the Abemaciclib Combination (Arm C), the Ribociclib Combination (Phase 1b and Arm C), and the Palbociclib Combination (Phase 1b): One or up to two prior hormonal therapies in the advanced or metastatic setting, one of which was in combination with a CDK4/6 inhibitor.

Additional Criteria for the Palbociclib Combination (Arm D), the Abemaciclib Combination (Arm D), and the Ribociclib Combination (Arm D): One or up to two prior hormonal therapies in the advanced or metastatic setting.

Additional Criteria for Capivasertib Combination (Phase 1b and Arm E): Recruitment in this combination will occur only in countries where capivasertib is locally approved and available.

1. PIK3CA/AKT1/PTEN-alteration as detected by an FDA and/or locally approved test (local result).
2. One or up to two prior hormonal therapies in the advanced or metastatic setting or participants who have radiological evidence of breast cancer recurrence or progression within 12 months from the end of adjuvant treatment with endocrine therapy, as these participants are considered as first line relapsed participants. Prior CDK4/6i treatment is allowed but not required.

Exclusion Criteria:

1. Active or newly diagnosed central nervous system metastases, or meningeal carcinomatosis. Note: Participants with stable brain or subdural metastases are allowed if the participant has completed local therapy and was on a stable or decreasing dose of corticosteroids at baseline for management of brain metastasis for at least 4 weeks before starting treatment in this study. The dose must be ≤2.0 mg/day of dexamethasone or equivalent. Any signs (for example, radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.
2. Participants with advanced, symptomatic visceral spread, who are at risk of life-threatening complications in the short term, including massive uncontrolled effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis, or liver involvement >50%.
3. Prior chemotherapy or elacestrant in the advanced/metastatic setting.
4. Participants with known germline BRCA mutation without prior treatment with a PARP inhibitor before study entry.
5. Prior therapy with elacestrant or other investigational selective estrogen receptor degraders, or investigational alike agents such as selective estrogen receptor modulators, selective estrogen receptor covalent antagonists, complete estrogen receptor antagonists, and proteolysis-targeting chimeras, in the metastatic setting. Prior treatment with fulvestrant is not exclusionary, except for Arm E, as it is an approved medication.
6. Participant has a concurrent malignancy or history of invasive malignancy within 3 years of enrollment, except basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix that has completed curative therapy. Other malignancies with low risk of recurrence may be considered eligible with Sponsor approval.

7. Uncontrolled significant active infections.

   • Participants with hepatitis B virus and/or hepatitis C virus infection must have undetectable viral load during screening.
   • Participants known to be human immunodeficiency virus+ are allowed if they have undetectable viral load at baseline.
8. Documented pneumonitis/interstitial lung disease prior to Cycle 1 Day 1.
9. Major surgery within 28 days before starting trial therapy.
10. Inability to take oral medications, refractory or chronic nausea, gastrointestinal conditions (including significant gastric or bowel resection), history of malabsorption syndrome, or any other uncontrolled gastrointestinal condition that impact the absorption of the study drug.
11. Known intolerance to elacestrant or any of its excipients.

12. Pregnant and breast-feeding women are excluded from the study. In addition, women of childbearing potential are excluded who:

    • Within 28 days before starting trial therapy, did not use a highly effective method of contraception.
    • Do not agree to use a highly effective method of contraception (Appendix F) or abstain from heterosexual intercourse throughout the entire study period and for 120 days after trial therapy discontinuation.
13. Men or women who do not agree to abstain from donating sperm or ova, or to use a highly effective method of contraception, 28 days prior, during the course of the treatment period and for 120 days after the last dose of study treatment.

14. Participant is currently receiving or received any of the following medications prior to first dose of trial therapy:

    • Anti-cancer therapy within 14 days (28 days for anticancer antibody based treatment) or 5 half-lives, whichever is shorter.

    Please note: Toxicity from prior therapy must be resolved to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 Grade ≤1, except alopecia and peripheral sensory neuropathy (Grade ≤2).

    • Known strong or moderate inducers or inhibitors of cytochrome P450 (CYP) 3A4 within 14 days or 5 half-lives, whichever is shorter, (refer to https://drug-interactions.medicine.iu.edu/maintable.aspx or https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers).
    • Herbal preparations/medications within 7 days. These include, but are not limited to, St. John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone, yohimbe, saw palmetto, and ginseng.
    • Vaccination, including but not limited to vaccination against COVID-19, during the 7 days prior to starting trial therapy.
15. Evidence of ongoing alcohol or drug abuse as assessed by the investigator.
16. Any severe medical or psychiatric condition that, in the Investigator's opinion, would preclude the participant's participation in a clinical study.

Additional Criteria for the Alpelisib Combination (Phase 1b and Arm A):

1. Prior therapy with alpelisib or any other phosphoinositide 3-kinase (PI3K) inhibitor.
2. Type 1 diabetes or uncontrolled type 2 diabetes (fasting plasma glucose level of >140 mg/dL [7.7 millimole (mmol)/L], or glycosylated hemoglobin [HbA1c] level of >6.4%).
3. Known intolerance to alpelisib or any of its excipients.
4. Participant is currently receiving or received drugs known to be a breast cancer resistant protein inhibitor (for example, curcumin, cyclosporine A, eltrombopag, febuxostat, fostamatinib, rolapitant, teriflunomide) within 14 days or 5 half-lives, whichever is shorter, prior to first dose of trial therapy (refer to Table 5.2 of https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers).
5. Participant has ongoing osteonecrosis of the jaw from previous or concurrent treatment with bisphosphonates or denosumab

Additional Criteria for the Everolimus Combination (Phase 1b and Arm B):

1. Prior therapy with everolimus.
2. Known intolerance to everolimus or any of its excipients.

Additional Criteria for the Abemaciclib Combination (Arm C):

1. Prior therapy with abemaciclib in the advanced or metastatic setting. Adjuvant therapy with abemaciclib is also exclusionary.
2. Known intolerance to abemaciclib or any of its excipients.
3. History of deep vein thrombosis or pulmonary embolism (unless on anticoagulation), cerebrovascular accident, or myocardial infarction, in the past 6 months. Participants on anticoagulation should have been on a stable dose for at least 3 months prior to enrollment.

Additional Criteria for the Ribociclib Combination (Phase 1b and Arm C):

1. Prior therapy with ribociclib in the advanced or metastatic setting. Prior adjuvant therapy with ribociclib is also exclusionary.
2. Known intolerance to ribociclib or any of its excipients.
3. QTcF interval corrected by Fridericia formula (QTcF) values ≥450 milliseconds (msec).

4. Participants who already have or who are at significant risk of developing QTc prolongation, including participants with:

   • Long QT syndrome
   • Uncontrolled or significant cardiac disease including recent (6 months) myocardial infarction, congestive heart failure, unstable angina, and brady-arrhythmias
   • Electrolyte abnormalities (K+, Ca++, Phos, Mg++) ≥Grade 1
5. Participant is currently receiving or received drugs known to prolong QT interval within 14 days or 5 half-lives, whichever is shorter, before the first dose of trial therapy.

Additional Criteria for the Palbociclib Combination (Phase 1b):

1. Prior therapy with palbociclib in the advanced or metastatic setting.
2. Known intolerance to palbociclib or any of its excipients

Additional Criteria for the Palbociclib Combination (Arm D):

1. Prior therapy with a CDK4/6i in the metastatic setting.
2. Known intolerance to palbociclib or any of its excipients.

Additional Criteria for the Abemaciclib Combination (Arm D):

1. Prior therapy with any CDK4/6i.
2. Known intolerance to abemaciclib or any of its excipients.

Additional Criteria for Ribociclib Combination (Arm D):

1. Prior therapy with a CDK4/6i in the advanced or metastatic setting.
2. Known intolerance to ribociclib or any of its excipients.
3. QTcF values ≥450 msec.

4. Participants who already have or who are at significant risk of developing QTc prolongation, including participants with:

   • Long QT syndrome
   • Uncontrolled or significant cardiac disease including recent (6 months) myocardial infarction, congestive heart failure, unstable angina, and brady-arrhythmias
   • Electrolyte abnormalities (K+, Ca++, Phos, Mg++) ≥Grade 1
5. Participant is currently receiving or received drugs known to prolong QT interval within 14 days or 5 half-lives, whichever is shorter, before the first dose of trial therapy.

Additional Criteria for Capivasertib Combination (Phase 1b and Arm E): Recruitment in this combination will occur only in countries where capivasertib is locally approved and available.

1. Prior treatment with any of the following: AKT, PI3K and mammalian target of rapamycin inhibitors and, for Arm E, fulvestrant.
2. Known intolerance to capivasertib or any of its excipients.
3. QTcF values ≥470 msec or factors that increase the risk of corrected QT interval (QTc) prolongation or risk of arrhythmic events such as heart failure, hypokalemia, potential for torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age, or any concomitant medication known to prolong the QT interval.
4. Clinically significant abnormalities of glucose metabolism as defined by any of the following: Participants with diabetes mellitus type 1; participants with diabetes mellitus type 2 requiring insulin treatment or participants with HbA1c level of >8.0% (63.9 mmol/mol).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1b Arm B: elacestrant with everolimus; Elacestrant Dihydrochloride 300 mg or 400 mg + Everolimus 5.0 mg, 7.5 mg or possibly 10 mg	Drug: Elacestrant; Elacestrant 86 mg, 172 mg, 258 mg or 345 mg once daily in cycles of 28 days; Drug: Everolimus; Everolimus 5 mg, 7.5 mg, or 10 mg once daily in cycles of 28 days; Other Names: Afinitor
Experimental: Phase 1b Arm E: Elacestrant Dihydrochloride 300 mg, 400 mg + Capivasertib 200 mg, 320 mg, 400 mg	Drug: Elacestrant; Elacestrant 86 mg, 172 mg, 258 mg or 345 mg once daily in cycles of 28 days; Drug: Capivasertib; Capivasertib 200 mg or 320 mg or 400 mg twice daily for 4 days on, 3 days off in cycles of 28 days; Other Names: Truqap
Experimental: Phase 1b Arm A: elacestrant with alpelisib; Elacestrant Dihydrochloride 300 milligrams (mg) or 400 mg + Alpelisib 150 mg to 250 mg	Drug: Elacestrant; Elacestrant 86 mg, 172 mg, 258 mg or 345 mg once daily in cycles of 28 days; Drug: Alpelisib; Alpelisib 150 mg or 250 mg once daily in cycles of 28 days; Other Names: Piqray
Experimental: Phase 1b Arm C: elacestrant with abemaciclib or ribociclib: Elacestrant Dihydrochloride 100 mg, 200 mg, 300 mg + Ribociclib 400 mg or possibly 600 mg The RP2D for the combination of elacestrant and abemaciclib is evaluated in the ongoing ELECTRA trial (ClinicalTrials.gov Identifier: NCT04791384)	Drug: Elacestrant; Elacestrant 86 mg, 172 mg, 258 mg or 345 mg once daily in cycles of 28 days; Drug: Ribociclib; Ribociclib 400 mg or 600 mg once daily for 21 days followed by 7 days off in cycles of 28 days; Other Names: Kisqali; Drug: Abemaciclib; Abemaciclib 100 mg or 150 mg twice daily in cycles of 28 consecutive days; Other Names: Verzenio
Experimental: Phase 1b Arm D: elacestrant with either palbociclib, abemaciclib, or ribociclib (no prior CDK4/6i); Elacestrant Dihydrochloride 300 mg or 400 mg + Palbociclib 100 mg,125 mg or the RP2D for the combination of elacestrant and abemaciclib is evaluated in the ongoing ELECTRA trial (ClinicalTrials.gov Identifier: NCT04791384) Elacestrant 86 mg, 172 mg, 258 mg + Ribociclib 400 mg or possibly 600 mg	Drug: Elacestrant; Elacestrant 86 mg, 172 mg, 258 mg or 345 mg once daily in cycles of 28 days; Drug: Ribociclib; Ribociclib 400 mg or 600 mg once daily for 21 days followed by 7 days off in cycles of 28 days; Other Names: Kisqali; Drug: Palbociclib; Palbociclib 100 mg or 125 mg once daily for 21 days followed by 7 days off in cycles of 28 days; Other Names: Ibrance; Drug: Abemaciclib; Abemaciclib 100 mg or 150 mg twice daily in cycles of 28 consecutive days; Other Names: Verzenio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with DLTs Observed During the First Cycle	Number of dose-limiting toxicities during the first cycle	28 days
Progression-free Survival	The time from the date of the first dose to the date of the first radiological documentation of disease progression or death, whichever comes first.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Time from the date of the first dose to the date of death from any cause	36 months
Duration of Response	Time from the date of the first documented CR/PR until the first radiological documentation of disease progression or death	36 months
Standard Pharmacokinetics (PK) Parameters Including AUC0-tau, Cmax, Tmax, and Ctrough	The plasma PK of elacestrant and each of the combination drugs	36 months
Overall Response Rate	Proportion of participants who achieve a best overall response of confirmed partial response (PR) or complete response (CR)	36 months
Clinical Benefit Rate	Proportion of participants who have the best overall response with a complete response, partial response or stable disease	36 months
Progression-free Survival Rate	Time from the date of the first dose to the date of the first radiological documentation of disease progression or death, whichever comes first	36 months

Collaborators and Investigators

• Sponsor: Stemline Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2023
• Primary Completion (Estimated): December 27, 2026
• Study Completion (Estimated): December 28, 2028

Study Registration Dates

• First Submitted: September 22, 2022
• First Submitted That Met QC Criteria: September 28, 2022
• First Posted (Actual): October 3, 2022

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 10, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: breast cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Organic Chemicals; Macrolides; Lactones; Sirolimus; Everolimus; abemaciclib; capivasertib; ribociclib; palbociclib; elacestrant; Alpelisib
• Other Study ID Numbers: STML-ELA-0222

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No