Lenvatinib in Combination With Pembrolizumab Versus Treatment of Physician's Choice in Participants With Advanced Endometrial Cancer (MK-3475-775/E7080-G000-309 Per Merck Standard Convention [KEYNOTE-775])

Phase 3

Active, not recruiting

• Conditions: Endometrial Neoplasms
• Interventions: Drug: Pembrolizumab; Drug: Paclitaxel; Drug: Lenvatinib; Drug: Doxorubicin

• Registration Number: NCT03517449
• Lead Sponsor: Eisai Inc.

Brief Summary

This is a study of pembrolizumab (MK-3475, KEYTRUDA®) in combination with lenvatinib (E7080) versus treatment of physician's choice (doxorubicin or paclitaxel) for the treatment of advanced endometrial cancer. Participants will be randomly assigned to receive either pembrolizumab and lenvatinib or treatment of physician's choice. The primary study hypothesis is that pembrolizumab in combination with lenvatinib prolongs progression free survival (PFS) and overall survival (OS) when compared to treatment of physician's choice.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-04-25
• Study First Submitted QC: 2018-04-25
• Study First Posted: 2018-05-07
• Study Start: 2018-06-11
• Primary Completion: 2020-10-26
• Results First Submitted: 2021-10-19
• Results First Submitted QC: 2021-10-19
• Results First Posted: 2021-11-17
• Status Verified: 2024-11
• Last Update Submitted: 2025-01-20
• Last Update Posted: 2025-01-22
• Study Completion: 2025-02-24

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 827

Inclusion Criteria

1. Has a histologically confirmed diagnosis of endometrial carcinoma (EC)

2. Documented evidence of advanced, recurrent or metastatic EC.

3. Has radiographic evidence of disease progression after 1 prior systemic, platinum-based chemotherapy regimen for EC. Participants may have received up to 1 additional line of platinum-based chemotherapy if given in the neoadjuvant or adjuvant treatment setting.

   Note: There is no restriction regarding prior hormonal therapy.

4. Has historical or fresh tumor biopsy specimen for determination of mismatch repair (MMR) status.

5. Has at least 1 measurable target lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and confirmed by Blinded Independent Central Review BICR.

6. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of starting study treatment.

7. Is not pregnant, breastfeeding, and agrees to use a highly effective method of contraception during the treatment period and for at least 120 days (for participants treated with lenvatinib plus pembrolizumab) or at least 180 days (for participants treated with treatment of physician's choice [TPC]) after the last dose of study treatment.

Exclusion Criteria

1. Has carcinosarcoma (malignant mixed mullerian tumor), endometrial leiomyosarcoma and endometrial stromal sarcomas.
2. Has unstable central nervous system (CNS) metastases.
3. Has active malignancy (except for endometrial cancer, definitively treated in-situ carcinomas [e.g. breast, cervix, bladder], or basal or squamous cell carcinoma of the skin) within 24 months of study start.
4. Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
5. Has a pre-existing greater than or equal (>=) Grade 3 gastrointestinal or non-gastrointestinal fistula.
6. Has radiographic evidence of major blood vessel invasion/infiltration.
7. Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study treatment.
8. Has a history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, cerebrovascular accident (CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability within 12 months of the first dose of study treatment.
9. Has an active infection requiring systemic treatment.
10. Has not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy.
11. Is positive for Human Immunodeficiency Virus (HIV).
12. Has active Hepatitis B or C.
13. Has a history of (non-infectious) pneumonitis that required treatment with steroids, or has current pneumonitis.
14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
15. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to study start -Has an active autoimmune disease (with the exception of psoriasis) that has required systemic treatment in the past 2 years.
16. Is pregnant or breastfeeding.
17. Has had an allogenic tissue/solid organ transplant.
18. Has received >1 prior systemic chemotherapy regimen (other than adjuvant or neoadjuvant) for Endometrial Cancer. Participants may receive up to 2 regimens of platinum-based chemotherapy in total, as long as one is given in the neoadjuvant or adjuvant treatment setting.
19. Has received prior anticancer treatment within 28 days of study start. All acute toxicities related to prior treatments must be resolved to Grade ≤1, except for alopecia and Grade ≤2 peripheral neuropathy.
20. Has received prior treatment with any treatment targeting VEGF-directed angiogenesis, any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
21. Has received prior treatment with an agent directed to a stimulatory or co-inhibitory T-cell receptor other than an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, and who has discontinued from that treatment due to a Grade 3 or higher immune-related adverse event.
22. Has received prior radiation therapy within 21 days of study start with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks of study start. Participants must have recovered from all radiation-related toxicities and/or complications prior to randomization.
23. Has received a live vaccine within 30 days of study start.
24. Has a known intolerance to study treatment (or any of the excipients).
25. Prior enrollment on a clinical study evaluating pembrolizumab and lenvatinib for endometrial carcinoma, regardless of treatment received.
26. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks of study start.
27. Participants with urine protein ≥1 gram (g)/24 hour.
28. Prolongation of corrected QT (QTc) interval to >480 milliseconds (ms).
29. Left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lenvatinib 20 mg + Pembrolizumab 200 mg	Pembrolizumab	Participants will receive pembrolizumab 200 milligram (mg) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle plus lenvatinib 20 mg administered orally (PO) once daily (QD) during each 21-day cycle for up to 35 cycles.
Lenvatinib 20 mg + Pembrolizumab 200 mg	Lenvatinib	Participants will receive pembrolizumab 200 milligram (mg) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle plus lenvatinib 20 mg administered orally (PO) once daily (QD) during each 21-day cycle for up to 35 cycles.
Treatment of Physician's Choice	Doxorubicin	Participants will receive either of the following treatments: doxorubicin 60 milligram per square meter (mg/m\^2) administered by IV on Day 1 of each 21-day cycle for up to a maximum cumulative dose of 500 mg/m\^2 OR paclitaxel 80 mg/m\^2 administered by IV on a 28-day cycle: 3 weeks receiving paclitaxel once a week and 1 week not receiving paclitaxel.
Treatment of Physician's Choice	Paclitaxel	Participants will receive either of the following treatments: doxorubicin 60 milligram per square meter (mg/m\^2) administered by IV on Day 1 of each 21-day cycle for up to a maximum cumulative dose of 500 mg/m\^2 OR paclitaxel 80 mg/m\^2 administered by IV on a 28-day cycle: 3 weeks receiving paclitaxel once a week and 1 week not receiving paclitaxel.

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From the date of randomization until the date of death from any cause or up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)	OS was defined as the time from the date of randomization to the date of death due to any cause. Participants who were lost to follow-up and those who were alive at the date of data cut-off were censored at the date the participant was last known alive, or date of data cut-off, whichever occurred first.
Progression-free Survival (PFS)	From the date of randomization to the date of the first documentation of disease progression or death, whichever occurred first or up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)	PFS was defined as the time from the date of randomization to the date of the first documentation of disease progression, as determined by Blinded Independent Central Review (BICR) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeter \[mm\]) in the sum of diameter of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.

Secondary Outcome Measures

Name	Time	Method
Model Predicted Area Under the Plasma Drug Concentration-time Curve (AUC) for Lenvatinib	Cycle 1 Day 1: 0.5-10 hours post-dose; Cycle 1 Day 15: 0-12 hours post-dose; Cycle 2 Day 1: 0.5-10 hours post-dose (each cycle length=21 days)	Sparse PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Individual predicted AUC for lenvatinib was then derived from the PK model. The data was collected and analyzed for lenvatinib plus pembrolizumab arm only.
Objective Response Rate (ORR)	From date of randomization up to first documentation of PD or date of death, whichever occurred first up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)	ORR was defined as the percentage of participants who had best overall response of either complete response (CR) or partial response (PR) as determined by BICR per RECIST 1.1. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (\<) 10mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Health-Related Quality of Life (HRQoL) Assessed by European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQC30) Score	At baseline (prior to first dose of study drug), on Day 1 of each subsequent cycle (cycle length of either 21 or 28 days), and at the post-treatment visit (up to 5 years and 5 months)	EORTC QLQ-C30 was a questionnaire which included 30 questions that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores are transformed to a range of 0 to 100 using a standard EORTC algorithm. A high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/quality of life (QoL) represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problem. Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2023).
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Immune-Related Adverse Events (irAEs)	From the first dose of study drug up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)	TEAEs was defined as AEs that occurred (or worsened, if present at Baseline) after the first dose of study drug through 28 days after the last dose of study drug. AE was defined as any untoward medical occurrence in a participants or clinical study participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. A SAE was defined as any untoward medical occurrence at any dose if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect. irAE was defined as any unfavorable and unintended immune-related sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.
Percentage of Participants Discontinued Study Treatment Due to TEAEs	From the first dose of study drug up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)	TEAEs was defined as those AEs that occurred (or worsened, if present at Baseline) after the first dose of study drug through 30 days after the last dose of study drug. An AE was defined as any untoward medical occurrence in a participants or clinical study participant temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Time to Treatment Failure Due to Toxicity	From the date of randomization to the date of discontinuation of study treatment due to TEAEs (up to 5 years 5 months)	Time to treatment failure due to toxicity was defined as the time from the date of randomization to the date a participant discontinued study treatment due to TEAEs. Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2023).
Model Predicted Apparent Total Clearance (CL/F) for Lenvatinib	Cycle 1 Day 1: 0.5-10 hours post-dose; Cycle 1 Day 15: 0-12 hours post-dose; Cycle 2 Day 1: 0.5-10 hours post-dose (each cycle length=21 days)	Sparse pharmacokinetic (PK) samples were collected and analyzed using a population PK approach to estimate PK parameters. Individual predicted CL/F for lenvatinib was then derived from the PK model. The data was collected and analyzed for lenvatinib plus pembrolizumab arm only.

Trial Locations

Locations (162)

North Shore University Health System; 🇺🇸 Evanston, Illinois, United States

Greater Baltimore Medical Center; 🇺🇸 Baltimore, Maryland, United States

University of Texas Southwestern Medical Center at Dallas; 🇺🇸 Dallas, Texas, United States

Royal Brisbane and Women s Hospital; 🇦🇺 Herston, Queensland, Australia

Sunnybrook Health Science Centre; 🇨🇦 Toronto, Ontario, Canada

Centre Armoricain de Radiotherapie Imagerie medicale et Oncologie; 🇫🇷 Plerin, France

Istituto Europeo di Oncologia; 🇮🇹 Milano, Italy

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

Centrum Onkologii Instytut im. Marii Sklodowskiej Curie; 🇵🇱 Gliwice, Poland

Barts Health NHS Trust - St Bartholomew s Hospital; 🇬🇧 London, United Kingdom

Ottawa General Hospital; 🇨🇦 Ottawa, Ontario, Canada

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

Texas Oncology-San Antonio Medical Center; 🇺🇸 San Antonio, Texas, United States

Centre Hospitalier Lyon Sud; 🇫🇷 Pierre Benite, France

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

St John of God; 🇦🇺 Subiaco, Western Australia, Australia

University of Rochester; 🇺🇸 Rochester, New York, United States

Azienda Ospedaliera per l Emergenza Cannizzaro; 🇮🇹 Catania, Italy

Hospital Privado de la Comunidad; 🇦🇷 Mar del Plata, Buenos Aires, Argentina

Hospital Aleman; 🇦🇷 Buenos Aires, Argentina

Centro de Oncologia e Investigacion Buenos Aires COIBA; 🇦🇷 Berazategui, Buenos Aires, Argentina

John Theurer Cancer Center at Hackensack University Med Ctr; 🇺🇸 Hackensack, New Jersey, United States

Tom Baker Cancer Centre; 🇨🇦 Calgary, Alberta, Canada

Jewish General Hospital; 🇨🇦 Montreal, Quebec, Canada

Hadassah Medical Center. Ein Kerem; 🇮🇱 Jerusalem, Israel

EISAI Trial Site 15; 🇯🇵 Toon, Ehime, Japan

Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals; 🇪🇸 Hospitalet de Llobregat, Barcelona, Spain

Florence Nightingale Gayrettepe Hastanesi; 🇹🇷 Istanbul, Turkey

Holy Name Medical Center; 🇺🇸 Teaneck, New Jersey, United States

Willamette Valley Cancer Institute and Research Center; 🇺🇸 Eugene, Oregon, United States

Sanford Gynecology Oncology; 🇺🇸 Sioux Falls, South Dakota, United States

Peter MacCallum Cancer Centre; 🇦🇺 Melbourne, Victoria, Australia

CIUSSS de l'Estrie-CHUS; 🇨🇦 Sherbrooke, Quebec, Canada

CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont; 🇨🇦 Montreal, Quebec, Canada

Fundacion Colombiana de Cancerologia Clinica Vida; 🇨🇴 Medellin, Colombia

EISAI Trial Site 1; 🇯🇵 Hidaka, Saitama, Japan

EISAI Trial Site 5; 🇯🇵 Kurume, Fukoka, Japan

Mater Misericordiae University Hospital; 🇮🇪 Dublin, Ireland

Edith Wolfson Medical Center; 🇮🇱 Holon, Israel

Clinica del Country; 🇨🇴 Bogota, Cundinamarca, Colombia

Instituto de Investigaciones Metabolicas; 🇦🇷 Buenos Aires, Argentina

Oncomedica S.A.; 🇨🇴 Monteria, Colombia

EISAI Trial Site 4; 🇯🇵 Morioka, Iwate, Japan

Rambam Medical Center; 🇮🇱 Haifa, Israel

EISAI Trial Site 13; 🇯🇵 Tokyo, Japan

Instituto de Oncologia Angel H. Roffo; 🇦🇷 Buenos Aires, Argentina

Biomelab S A S; 🇨🇴 Barranquilla, Colombia

Chaim Sheba Medical Center; 🇮🇱 Ramat Gan, Israel

EISAI Trial Site 18; 🇯🇵 Kashiwa, Chiba, Japan

Centre Hospitalier de l Universite de Montreal - CHUM; 🇨🇦 Montreal, Quebec, Canada

EISAI Trial Site 2; 🇯🇵 Sunto-gun, Shizuoka, Japan

Fundacion Valle del Lili; 🇨🇴 Cali, Valle Del Cauca, Colombia

EISAI Trial Site 6; 🇯🇵 Tokyo, Japan

EISAI Trial Site 3; 🇯🇵 Niigata, Japan

Soroka Medical Center; 🇮🇱 Beer Sheva, Israel

Rabin Medical Center; 🇮🇱 Petah Tikva, Israel

EISAI Trial Site 7; 🇯🇵 Matsuyama, Ehime, Japan

EISAI Trial Site 11; 🇯🇵 Sapporo, Hokkaido, Japan

EISAI Trial Site 17; 🇯🇵 Tsukuba, Ibaraki, Japan

Centrum Onkologii. Instytut im. Marii Sklodowskiej-Curie; 🇵🇱 Warszawa, Mazowieckie, Poland

Beskidzkie Centrum Onkologii im. Jana Pawla II; 🇵🇱 Bielsko-Biala, Poland

Mordovia Republican Oncological Dispensary; 🇷🇺 Saransk, Russian Federation

Basken Adana Dr.Turgut Noyan Uygulama ve Arastirma Merkezi; 🇹🇷 Adana, Turkey

Acibadem Bursa Hastanesi; 🇹🇷 Bursa, Turkey

EISAI Trial Site 19; 🇯🇵 Isehara, Kanagawa, Japan

EISAI Trial Site 14; 🇯🇵 Sendai, Miyagi, Japan

EISAI Trial Site 16; 🇯🇵 Kagoshima, Japan

Grupo Medico Camino SC; 🇲🇽 Mexico City, Mexico

Szpital Morski im. PCK Szpitale Wojewodzkie w Gdyni Sp. z o.o.; 🇵🇱 Gdynia, Poland

SPb SBHI City Clinical Oncological Dispensary; 🇷🇺 Saint Petersburg, Russian Federation

Tomsk National Research Medical Center of Russian Academy of Sciences; 🇷🇺 Tomsk, Russian Federation

Kaohsiung Veterans General Hospital; 🇨🇳 Kaohsiung, Taiwan

EISAI Trial Site 10; 🇯🇵 Tokyo, Japan

Alivia Clinica de Alta Especialidad S.A. de C.V.; 🇲🇽 Monterrey, Nuevo Leon, Mexico

Pomorski Uniwersytet Medyczny w Szczecinie; 🇵🇱 Szczecin, Poland

Hacettepe University Medical Faculty; 🇹🇷 Ankara, Turkey

Ege Universitesi Tip Fakultesi; 🇹🇷 Izmir, Turkey

National Cancer Center; 🇰🇷 Goyang-si, Gyeonggi-do, Korea, Republic of

Faicic S de RL de CV; 🇲🇽 Veracruz, Mexico

Republican Clinical Oncology Dispensary of Tatarstan MoH; 🇷🇺 Kazan, Russian Federation

Republican Clinical Oncology Dispensary of Republic of Bashkortostan; 🇷🇺 Ufa, Russian Federation

Taipei Veterans General Hospital; 🇨🇳 Taipei, Beitou, Taiwan

Chang Gung Medical Foundation. Linkou Branch; 🇨🇳 Taoyuan, Taiwan

FSBI National Medical Oncology Research Center n.a. N.N. Blokhina; 🇷🇺 Moscow, Russian Federation

Cancer Care Manitoba; 🇨🇦 Winnipeg, Manitoba, Canada

University of California Los Angeles; 🇺🇸 Santa Monica, California, United States

University of Miami Health System; 🇺🇸 Miami, Florida, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Maryland Oncology Hematology, P.A.; 🇺🇸 Wheaton, Maryland, United States

Instituto Medico Especializado Alexander Fleming; 🇦🇷 Buenos Aires, Argentina

Centro Oncologico Riojano Integral; 🇦🇷 La Rioja, Argentina

Royal North Shore Hospital; 🇦🇺 Sydney, New South Wales, Australia

Hospital Araujo Jorge; 🇧🇷 Goiania, GO, Brazil

Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs; 🇧🇷 Porto Alegre, RS, Brazil

Hospital de Clinicas de Porto Alegre; 🇧🇷 Porto Alegre, RS, Brazil

Instituto Nacional do Cancer II; 🇧🇷 Rio de Janeiro, RJ, Brazil

Fundacao Dr Amaral Carvalho; 🇧🇷 Jau, SP, Brazil

Instituto do Cancer de Sao Paulo - ICESP; 🇧🇷 Sao Paulo, SP, Brazil

Faculdade de Medicina da Universidade Federal de Minas Gerais; 🇧🇷 Belo Horizonte, Brazil

Clinica de Pesquisas e Ctro de Estudos Onc. Ginecol. e Mamaria Ltda; 🇧🇷 Sao Paulo, SP, Brazil

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

CHU de Quebec-Universite Laval-Hotel Dieu de Quebec; 🇨🇦 Quebec, Canada

Clinica Colsanitas S.A. - Sede Clinica Universitaria Colombia; 🇨🇴 Bogota, Colombia

Rodrigo Botero SAS; 🇨🇴 Medellin, Colombia

Institut Bergonie; 🇫🇷 Bordeaux, France

Groupe Hospitalier Broca Cochin Hotel Dieu; 🇫🇷 Paris, France

Centre de Lutte Contre le Cancer Francois Baclesse; 🇫🇷 Caen, France

Centre Oscar Lambret; 🇫🇷 Lille, France

Centre Leon Berard; 🇫🇷 Lyon, France

Hopital prive du Confluent; 🇫🇷 Nantes, France

Centre Eugene Marquis; 🇫🇷 Rennes, France

Institut Regional du Cancer de Montpellier - ICM; 🇫🇷 Montpellier, France

Hopital Diaconesses Croix Saint Simon; 🇫🇷 Paris, France

Institut Gustave Roussy; 🇫🇷 Villejuif, France

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori; 🇮🇹 Meldola, Italy

Ospedale San Raffaele; 🇮🇹 Milano, Italy

Istituto Nazionale Tumori IRCCS Fondazione Pascale; 🇮🇹 Napoli, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori; 🇮🇹 Milan, Italy

Policlinico Universitario Agostino Gemelli; 🇮🇹 Roma, Italy

EISAI Trial Site 9; 🇯🇵 Nagoya, Aichi, Japan

EISAI Trial Site 8; 🇯🇵 Akashi, Hyogo, Japan

EISAI Trial Site 12; 🇯🇵 Tokyo, Japan

Szpital Kliniczny im Ks Anny Mazowieckiej; 🇵🇱 Warszawa, Poland

Investigacion Onco Farmaceutica S de RL de CV; 🇲🇽 La Paz, Baja California, Mexico

Auckland City Hospital; 🇳🇿 Auckland, New Zealand

Centro Hemato Oncologico Privado; 🇲🇽 Toluca, Mexico

Instytut Centrum Zdrowia Matki Polki; 🇵🇱 Lodz, Poland

FSBI-FRCC of Special Types Med. Care & Technologies FMBA of Russia; 🇷🇺 Moscow, Russian Federation

Altay Regional Oncology Dispensary; 🇷🇺 Barnaul, Russian Federation

Leningrad Regional Oncology Center; 🇷🇺 Saint-Petersburg, Russian Federation

Hospital Ramon y Cajal; 🇪🇸 Madrid, Spain

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

Hospital Universitario Gregorio Maranon; 🇪🇸 Madrid, Spain

Clinica Universitaria Navarra - Madrid; 🇪🇸 Madrid, Spain

Hospital Clinico San Carlos; 🇪🇸 Madrid, Spain

Hospital Universitario y Politecnico La Fe de Valencia; 🇪🇸 Valencia, Spain

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Kaohsiung Chang Gung Memorial Hospital of the C.G.M.F.; 🇨🇳 Kaohsiung, Taiwan

Taichung Veterans General Hospital; 🇨🇳 Taichung, Taiwan

Acibadem Universitesi Atakent Hastanesi; 🇹🇷 Istanbul, Turkey

Baskent Universitesi Ankara Hastanesi; 🇹🇷 Ankara, Turkey

Addenbrookes Hospital; 🇬🇧 Cambridge, United Kingdom

Royal Sussex County Hospital; 🇬🇧 Brighton, United Kingdom

University Hospital Southampton NHS Foundation Trust; 🇬🇧 Southampton, United Kingdom

Imperial College Healthcare NHS Trust; 🇬🇧 London, United Kingdom

The Royal Marsden Foundation Trust; 🇬🇧 London, United Kingdom

The Royal Marsden NHS Foundation Trust; 🇬🇧 London, United Kingdom

Guy s & St Thomas NHS Foundation Trust; 🇬🇧 London, United Kingdom

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

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

Georgia Cancer Center at Augusta University; 🇺🇸 Augusta, Georgia, United States

Arizona Oncology Associates, PC- HAL; 🇺🇸 Phoenix, Arizona, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Smilow Cancer Hospital at Yale New Haven; 🇺🇸 New Haven, Connecticut, United States

Florida Hospital Cancer Institute; 🇺🇸 Orlando, Florida, United States

University Medical Center New Orleans; 🇺🇸 New Orleans, Louisiana, United States

Stephenson Cancer Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Texas Oncology-South Austin; 🇺🇸 Austin, Texas, United States

Utah Cancer Specialists; 🇺🇸 Salt Lake City, Utah, United States

University College Hospital; 🇬🇧 London, United Kingdom

UT West Cancer Center; 🇺🇸 Germantown, Tennessee, United States