Open-Label Umbrella Study To Evaluate Safety And Efficacy Of Elacestrant In Various Combination In Patients With Metastatic Breast Cancer

Phase 1

Recruiting

• Conditions: Breast Cancer; Metastatic Breast Cancer
• Interventions: Drug: Elacestrant; Drug: Ribociclib; Drug: Everolimus; Drug: Alpelisib; Drug: Capivasertib; Drug: Palbociclib; Drug: Abemaciclib

• Registration Number: NCT05563220
• Lead Sponsor: Stemline Therapeutics, Inc.

Brief Summary

This is a multicenter, Phase 1b/2 trial. The phase 1b part of the trial aims to determine the RP2D of elacestrant when administered in combination with alpelisib, everolimus, palbociclib, abemaciclib, and ribociclib. The Phase 2 part of the trial will evaluate the efficacy and safety of the various combinations in patients with ER+/HER2- advanced/metastatic breast cancer.

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 patients experiencing a DLT of elacestrant when administered in combination with alpelisib, everolimus, palbociclib, abemaciclib, and ribociclib, that is, ≤1 patient experiencing a DLT out of 6 DLT evaluable patients. For each combination, this phase will have between 1 and 3 cohorts of 6 DLT-evaluable patients each. The total number of DLT-evaluable patients in all the combinations will vary between 24 and 72.

The Phase 2 part of the trial will evaluate the efficacy and safety of the various combinations in patients with ER+/HER2- advanced/metastatic breast cancer.

The treatment arms will be:

* Arm A: 50 patients: elacestrant with alpelisib;

* Arm B: 50 patients: elacestrant with everolimus;

* Arm C: 60 patients (30 patients in each combination): elacestrant with either abemaciclib or ribociclib;

* Arm D: 90 patients (30 patients in each combination): elacestrant with either palbociclib, abemaciclib, or ribociclib

* Arm E: 60 patients: elacestrant with capivasertib

Phase 1b will have a total of 90 patients, while Phase 2 will have 310 patients for all treatment arm combinations.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2022-09-22
• Study First Submitted QC: 2022-09-28
• Study First Posted: 2022-10-03
• Study Start: 2023-01-24
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-21
• Last Update Posted: 2024-12-27
• Primary Completion: 2024-12-31
• Study Completion: 2026-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

1. Patient 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 patients may be of any menopausal status.

   • Postmenopausal status is defined by:

     1. Age ≥60 years
     2. Age <60 years and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) or a follicle-stimulating hormone (FSH) value >40 mIU/mL and an estradiol value<40 pg/mL (140 pmol/L) or in postmenopausal ranges per local reference ranges
     3. Documentation of prior surgical sterilization (i.e., bilateral tubal ligation, total hysterectomy, or 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 concurrently receiving a luteinizing hormone-releasing hormone (LHRH) agonist initiated at least 4 weeks before the start of trial therapy and are planning to continue LHRH agonist treatment during the study treatment.

   • For perimenopausal women to be considered of non-childbearing potential, FSH levels must be >40 mIU/ml.

3. Histopathological or cytological confirmed ER+, HER2-, breast cancer, per local laboratory, as per the American Society of Clinical Oncology (ASCO)/College of American Pathologists(CAP) guidelines (Allison et al, 2020, Wolff et al, 2018). 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 PGR positivity. .

4. At least 1 not previously irradiated measurable lesion as per RECIST version 1.1 and/or at least 1 lytic or mixed (lytic +sclerotic) bone lesion with identifiable soft tissue components meeting the definition of measurability by RECIST version 1.1 that can be evaluated by CT or MRI; patients with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible.

5. ECOG performance status of 0 or 1.

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

   1. Absolute neutrophil count (ANC) ≥1.5 × 10^9/L

   2. Platelets ≥100 × 10^9/L

   3. Hemoglobin ≥9.0 g/dL

   4. Potassium, sodium, calcium (corrected for serum albumin) and magnesium CTCAE grade ≤1

   5. Creatinine is ≤ 1.5 x ULN or if creatinine is > 1.5 x ULN, then creatinine clearance must be ≥50 mL/min based on the Cockcroft-Gault formula. Note: C-G formula:

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

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

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

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

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Exclusion Criteria

1. Active or newly diagnosed CNS metastases, including meningeal carcinomatosis. Note: Patients with stable brain or subdural metastases are allowed if the patient 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 (e.g., radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.

2. Patients with advanced, symptomatic visceral spread, that 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. Patients 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 (SERDs), or investigational alike agents such as selective estrogen receptor modulators (SERM), selective estrogen receptor covalent antagonists (SERCANs), complete estrogen receptor antagonists (CERANs), and proteolysis-targeting chimeras (PROTACs), in the metastatic setting. Prior treatment with fulvestrant is not exclusionary as it is an approved medication.

6. Patient 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. • Patients with HBV and/or HCV infection must have undetectable viral load during screening.

   • Patients known to be HIV+ are allowed if they have undetectable viral load at baseline.

8. Documented pneumonitis/ILD 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, during the course of the treatment period and for 120 days after the last dose of study treatment.

14. Patient 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 NCI CTCAE 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 http://medicine.iupui.edu/clinpharm/ddis/ 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 (DHEA), yohimbe, saw palmetto, and ginseng.

    • Vaccination, including but not limited to vaccination against COVID-19, during the 7 days prior to randomization.

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 patient's participation in a clinical study.

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

Inclusion:

In general, the SmPC of the respective combination drug should be consulted for instructions/restrictions with respect to interactions with concomitant medications.

1. 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 CDK4/6 inhibitor.

Exclusion:

1. Prior therapy with alpelisib or any other PI3K inhibitor.
2. Type 1 diabetes or uncontrolled type 2 diabetes (fasting plasma glucose level of >140 mg/dL [7.7 mmol/L], or glycosylated hemoglobin [HbA1c] level of >6.4%).
3. Known intolerance to alpelisib or any of its excipients.
4. Patient is currently receiving or received drugs known to be a BCRP inhibitor within 14 days or 5 half-lives, whichever is shorter, prior to first dose of trial therapy
5. Patient has ongoing osteonecrosis of the jaw from previous or concurrent treatment with bisphosphonates or denosumab

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

Inclusion:

1. 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.

Exclusion:

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

Additional Eligibility for the Abemaciclib Combination (Arm C)

Inclusion:

1. 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.

Exclusion:

1. Prior therapy with abemaciclib in the advanced or metastatic setting. Adjuvant therapy with abemaciclib is exclusionary if the patient relapsed within the past 12 months.
2. Known intolerance to abemaciclib or any of its excipients.

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

Inclusion:

1. 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.

Exclusion:

1. Prior therapy with ribociclib in the metastatic setting. Prior adjuvant therapy with ribociclib is also exclusionary if the patient relapsed within the past 12 months.

2. Known intolerance to ribociclib or any of its excipients.

3. QTcF values ≥450 msec.

4. Patients who already have or who are at significant risk of developing QTc prolongation, including patients 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

5. Patient 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 Eligibility for the Palbociclib Combination (Phase 1b)

Inclusion:

1. 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.

Exclusion:

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

Additional Eligibility for the Palbociclib Combination (Arm D)

Inclusion:

1. One or up to two prior hormonal therapies in the advanced or metastatic setting.

Exclusion:

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

Additional Eligibility for the Abemaciclib Combination (Arm D)

Inclusion:

1. One or up to two prior hormonal therapies in the advanced or metastatic setting.

Exclusion:

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

Additional Eligibility for Ribociclib Combination (Arm D)

Inclusion:

1. One or up to two prior hormonal therapies in the advanced or metastatic setting.

Exclusion:

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. Patients who already have or who are at significant risk of developing QTc prolongation, including patients 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

5. Patient 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 1b Arm C: elacestrant with abemaciclib or ribociclib:	Ribociclib	Elacestrant Dihydrochloride 100 mg, 200 mg, 300 mg + Ribociclib 400 mg or possibly 600 mg The recommended Phase 2 dose for the combination of elacestrant and abemaciclib is evaluated in the ongoing ELECTRA trial (ClinicalTrials.gov Identifier: NCT04791384)
Phase 1b Arm D: elacestrant with either palbociclib, abemaciclib, or ribociclib (no prior CDK4/6i)	Abemaciclib	Elacestrant Dihydrochloride 300 mg or 400 mg + Palbociclib 100 mg,125 mg OR The recommended Phase 2 dose 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
Phase 1b Arm B: elacestrant with everolimus	Everolimus	Elacestrant Dihydrochloride 300 mg or 400 mg + Everolimus 5.0 mg, 7.5 mg or possibly 10 mg
Phase 1b Arm A: elacestrant with alpelisib	Elacestrant	Elacestrant Dihydrochloride 300 mg or 400 mg + Alpelisib 250 mg or 300 mg
Phase 1b Arm A: elacestrant with alpelisib	Alpelisib	Elacestrant Dihydrochloride 300 mg or 400 mg + Alpelisib 250 mg or 300 mg
Phase 1b Arm B: elacestrant with everolimus	Elacestrant	Elacestrant Dihydrochloride 300 mg or 400 mg + Everolimus 5.0 mg, 7.5 mg or possibly 10 mg
Phase 1b Arm C: elacestrant with abemaciclib or ribociclib:	Elacestrant	Elacestrant Dihydrochloride 100 mg, 200 mg, 300 mg + Ribociclib 400 mg or possibly 600 mg The recommended Phase 2 dose for the combination of elacestrant and abemaciclib is evaluated in the ongoing ELECTRA trial (ClinicalTrials.gov Identifier: NCT04791384)
Phase 1b Arm D: elacestrant with either palbociclib, abemaciclib, or ribociclib (no prior CDK4/6i)	Elacestrant	Elacestrant Dihydrochloride 300 mg or 400 mg + Palbociclib 100 mg,125 mg OR The recommended Phase 2 dose 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
Phase 1b Arm C: elacestrant with abemaciclib or ribociclib:	Abemaciclib	Elacestrant Dihydrochloride 100 mg, 200 mg, 300 mg + Ribociclib 400 mg or possibly 600 mg The recommended Phase 2 dose for the combination of elacestrant and abemaciclib is evaluated in the ongoing ELECTRA trial (ClinicalTrials.gov Identifier: NCT04791384)
Phase 1b Arm D: elacestrant with either palbociclib, abemaciclib, or ribociclib (no prior CDK4/6i)	Ribociclib	Elacestrant Dihydrochloride 300 mg or 400 mg + Palbociclib 100 mg,125 mg OR The recommended Phase 2 dose 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
Phase 1b Arm D: elacestrant with either palbociclib, abemaciclib, or ribociclib (no prior CDK4/6i)	Palbociclib	Elacestrant Dihydrochloride 300 mg or 400 mg + Palbociclib 100 mg,125 mg OR The recommended Phase 2 dose 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
Phase 1b Arm E:	Elacestrant	Elacestrant Dihydrochloride 300 mg, 400 mg + Capivasertib 200 mg, 320 mg, 400 mg
Phase 1b Arm E:	Capivasertib	Elacestrant Dihydrochloride 300 mg, 400 mg + Capivasertib 200 mg, 320 mg, 400 mg

Primary Outcome Measures

Name	Time	Method
Estimation of PFS rate at 6 months	6 months	PFS rate for each of the combination arms in patients who received prior ET and CDK4/6i in the metastatic setting
Number of DLTs observed during the first cycle	28 days	Number of dose-limiting toxicities during the first cycle

Secondary Outcome Measures

Name	Time	Method
Overall Survival	36 months	Time from the date of the first dose to the date of death from any cause
Overall Response Rate	36 months	Proportion of patients who achieve a best overall response (BOR) of confirmed partial response (PR) or complete response (CR)
Duration of Response	36 months	Time from the date of the first documented CR/PR until the first radiological documentation of disease progression or death
Progression-free survival	36 months	Time from the date of the first dose to the date of the first radiological documentation of disease progression or death, whichever occurs first
Standard PK parameters including AUC0-tau, Cmax, Tmax, and Ctrough	36 months	The plasma PK of elacestrant and each of the combination drugs
Clinical Benefit Rate	36 months	Proportion of patients who have the best overall response with a complete response, partial response or stable disease

Trial Locations

Locations (113)

Kliniken Essen-Mitte (KEM); 🇩🇪 Essen, Germany

Gesundheit Nordhessen Klinikum Kassel; 🇩🇪 Kassel, Germany

Universitaetsklinikum Tuebingen; 🇩🇪 Tübingen, Germany

Semmelweis Egyetem Klinikai Kozpont - Onkologiai Intezet; 🇭🇺 Budapest, Hungary

Orszagos Onkologiai Intezet; 🇭🇺 Budapest, Hungary

Samson Assuta Ashdod University Hospital - The Institute of Oncology; 🇮🇱 Ashdod, Israel

Marienhospital Bottrop; 🇩🇪 Bottrop, Germany

Azienda Ospedaliero-Universitaria Pisana; 🇮🇹 Pisa, Italy

Klinika Onkologii; Wojskowy Instytut Medyczny - Państwowy Instytut Badawczy; 🇵🇱 Warszawa, Mazowieckie, Poland

Dothan Hematology and Oncology; 🇺🇸 Dothan, Alabama, United States

Mayo Clinic - Arizona; 🇺🇸 Phoenix, Arizona, United States

Highlands Oncology Group; 🇺🇸 Springdale, Arkansas, United States

OPN Healthcare (Arcadia Location); 🇺🇸 Arcadia, California, United States

Glendale Adventist; 🇺🇸 Glendale, California, United States

OPN Healthcare (Los Alamitos Location); 🇺🇸 Los Alamitos, California, United States

Cedars Sinai; 🇺🇸 Los Angeles, California, United States

UCLA UCLA Hem/Onc - Clinical Research Unit; 🇺🇸 Los Angeles, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center; 🇺🇸 San Francisco, California, United States

TOI Clinical Research; 🇺🇸 Whittier, California, United States

Rocky Mountain Cancer Centers; 🇺🇸 Lone Tree, Colorado, United States

Yale School Of Medicine - Smilow Cancer Hospital - Breast Center; 🇺🇸 New Haven, Connecticut, United States

George Washington Cancer Center; 🇺🇸 Washington, District of Columbia, United States

Advent Health (Florida Hospital) - Altamonte Springs; 🇺🇸 Altamonte Springs, Florida, United States

Mayo Clinic - Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Ocala Oncology; 🇺🇸 Ocala, Florida, United States

Northside Hospital Atlanta Cancer Care; 🇺🇸 Cumming, Georgia, United States

Northwestern Feinberg Scholl of Medicine Prentice Women's Hospital; 🇺🇸 Chicago, Illinois, United States

Fort Wayne Medical Oncology and Hematology; 🇺🇸 Fort Wayne, Indiana, United States

MD Alliance for Multispecialty Research, LLC; 🇺🇸 Merriam, Kansas, United States

New England Cancer Specialists; 🇺🇸 Scarborough, Maine, United States

Johns Hopkins School of Medicine; 🇺🇸 Baltimore, Maryland, United States

Universitatskinikum Carl Gustav Carus Dresden; 🇩🇪 Dresden, Germany

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Barbara Ann Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Minnesota Oncology Hematology; 🇺🇸 Minneapolis, Minnesota, United States

Mayo Clinic - Rochester; 🇺🇸 Rochester, Minnesota, United States

Washington University School of Medicine in St. Louis; 🇺🇸 Saint Louis, Missouri, United States

Astera Cancer Care; 🇺🇸 East Brunswick, New Jersey, United States

Summit Medical Group; 🇺🇸 Florham Park, New Jersey, United States

Cooperman Barnabas Medical Center; 🇺🇸 New Brunswick, New Jersey, United States

NYU Langone Health; 🇺🇸 New York, New York, United States

New York Cancer and Blood Specialists; 🇺🇸 Port Jefferson Station, New York, United States

W&IH of RI Breast Health Center of Women and Infants Hospital of Rhode Island; 🇺🇸 Providence, Rhode Island, United States

Sarah Cannon Research Institute / Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

Texas Oncology - Baylor Charles A. Sammons Cancer Center; 🇺🇸 Dallas, Texas, United States

MD Anderson Cancer Center Texas; 🇺🇸 Houston, Texas, United States

UT Health San Antonio; 🇺🇸 San Antonio, Texas, United States

Inova Schar Cancer Institute; 🇺🇸 Fairfax, Virginia, United States

Virginia Cancer Specialists; 🇺🇸 Fairfax, Virginia, United States

Virginia Oncology Associates; 🇺🇸 Norfolk, Virginia, United States

Cancer Care Northwest; 🇺🇸 Spokane Valley, Washington, United States

Northwest Medical Specialties (Nwms) - Puyallup - Medical Oncology (Rainier Hematology-Oncology)/Exigent Research Network; LLC; 🇺🇸 Tacoma, Washington, United States

University of WI - Carbone Cancer Center (Phase II only); 🇺🇸 Madison, Wisconsin, United States

Centro Medico Austral; 🇦🇷 Buenos Aires, Argentina

Hospital Britanico De Buenos Aires; 🇦🇷 Buenos Aires, Argentina

Cemaic - Centro De Especialidades Medicas Ambulatorias E Investigacion Clinica; 🇦🇷 Cordoba, Argentina

Centro Oncologico Riojano Integral (Cori); 🇦🇷 La Rioja, Argentina

Macquarie University; 🇦🇺 Sydney, Australia

Institut Jules Bordet; 🇧🇪 Anderlecht, Belgium

Grand Hôpital de Charleroi - Site Notre Dame; 🇧🇪 Charleroi, Belgium

Universitaire Ziekenhuizen (Uz) Leuven - Campus Gasthuisberg - Multidisciplinair Borstcentrum (Multidisciplinary Breast Center) (Mbc); 🇧🇪 Leuven, Belgium

Algemeen Ziekenhuis Nikolaas; VITAZ; Oncologie Klinisch Studiecentrum; 🇧🇪 Sint-Niklaas, Belgium

ACCG - Hospital Araujo Jorge; 🇧🇷 Goiania, Brazil

Clinica Neoplasias Litoral; 🇧🇷 Itajai, Brazil

Hospital Sao Lucas da PUCRS; 🇧🇷 Porto Alegre, Brazil

Centro Gaucho Integrado de Oncologia; Hematologia; Ensino e Pesquisa - Hospital Mae de Deus/AESC; 🇧🇷 Porto Alegre, Brazil

Hospital Sirio-Libanes (HSL) - Centro De Oncologia - Sao Paulo; 🇧🇷 Sao Paulo, Brazil

Nemocnice Horovice Hospital; 🇨🇿 Hořovice, Czechia

Fakultni Nemocnice Olomouc; 🇨🇿 Olomouc, Czechia

Centre Hospitalier Lyon SUD- HCL; 🇫🇷 Lyon, France

Centre de Cancérologie du Grand Montpellier; 🇫🇷 Rouen, France

Centre Hospitalier Universitaire (Chu) De Toulouse - Institut Universitaire Du Cancer De Toulouse-Oncopole (Iuct-Oncopole) (Institut Claudius Regaud); 🇫🇷 Toulouse, France

Institut Gustave-Roussy-Umr 981; 🇫🇷 Villejuif, France

Universitaetsklinikum Mannheim; 🇩🇪 Mannheim, Baden-Wuerttemberg, Germany

Rambam Heath; 🇮🇱 Haifa, Israel

Shaare Zedek Medical Center; 🇮🇱 Jerusalem, Israel

Davidoff Rabin Medical Center; 🇮🇱 Petah Tikva, Israel

Sheba Medical Center; Center Israel; 🇮🇱 Ramat Gan, Israel

ASST degli Spedali Civili di Brescia; 🇮🇹 Brescia, Italy

Azienda Ospedaliera "Istituti Ospitalieri" Di Cremona; 🇮🇹 Cremona, Italy

Istituto Nazionale Tumori "Fondazione PASCALE"; 🇮🇹 Napoli, Italy

Ospedale Infermi di Rimini - Azienda Unita Sanitaria Locale Della Romagna; 🇮🇹 Rimini, Italy

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Gangnam Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

The Catholic University of Korea - Seoul St. Mary's Hospital; 🇰🇷 Seoul, Korea, Republic of

Korea University Anam Hospital; 🇰🇷 Seoul, Korea, Republic of

Ulsan University Hospital; 🇰🇷 Ulsan, Korea, Republic of

Centre Hospitalier De L'Ardenne; 🇱🇺 Libramont, Luxembourg

Przychodnia Lekarska "Komed" Roman Karaszewski; 🇵🇱 Konin, Poland

Med-Polonia Sp. Z o.o.; 🇵🇱 Poznań, Poland

Instytut Centrum Zdrowia Matki Polki; 🇵🇱 Łódź, Poland

Complejo Hospitalario Universitario A Coruna; 🇪🇸 A Coruña, Spain

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Clinic Barcelona; 🇪🇸 Barcelona, Spain

Hospital General Universitario Gregorio Maranon; 🇪🇸 Madrid, Spain

IOB Madrd Institute of Oncology Hospital Beata Maria Ana de Jesus; 🇪🇸 Madrid, Spain

Hospital Clinico San Carlos; 🇪🇸 Madrid, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Universitario Virgen de la Victoria; 🇪🇸 Malaga, Spain

NEXT Madrid; 🇪🇸 Pozuelo de Alarcon, Spain

Fundacion Instituto Valeciano De Oncologia; 🇪🇸 Valencia, Spain

Hospital Clinico Universitario de Valencia; 🇪🇸 Valencia, Spain

Hospital Arnau De Vilanova; 🇪🇸 Valencia, Spain

Abdurrahman Yurtaslan Oncology Hospital; 🇹🇷 Ankara, Turkey

Ankara Bilkent City Hospital, Bilkent Campus, Universiteler Mh. (old: Ankara Yildirim Beyazit Universitesi); 🇹🇷 Ankara, Turkey

The Clatterbridge Cancer Centre NHS Foundation Trust; 🇬🇧 Liverpool, United Kingdom

Liverpool Hospital; 🇬🇧 Liverpool, United Kingdom

North Middlesex University Hospital; 🇬🇧 London, United Kingdom

Sarah Cannon Research Institute UK; Ltd; 🇬🇧 London, United Kingdom

University College London Hospitals NHS Foundation Trust; The London Clinic - Main Hospital; 🇬🇧 London, United Kingdom