Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (MK-7902/E7080) in Adults With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Treatment-naïve Nonsmall Cell Lung Cancer (NSCLC) (MK-7902-007/E7080-G000-314/LEAP-007)
- Conditions
- Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT03829332
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combined with lenvatinib (MK-7902/E7080) compared to pembrolizumab alone (with placebo for lenvatinib) in treatment-naïve adults with no prior systemic therapy for their metastatic non-small cell lung cancer (NSCLC) whose tumors have a programmed cell death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) greater than or equal to 1%.
The primary study hypotheses are that: 1) the combination of pembrolizumab and lenvatinib is superior to pembrolizumab alone as assessed by Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1); and 2) the combination of pembrolizumab and lenvatinib is superior to pembrolizumab alone as assessed by Overall Survival (OS).
- Detailed Description
As of 30-Jul-2021, active participants, investigator, and sponsor personnel or delegate(s) involved in the treatment administration or clinical evaluation of the participants will be unblinded. Participants will discontinue lenvatinib and placebo, and participants who remain on treatment will receive open-label pembrolizumab only.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 623
- Has a histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)
- Has Stage IV NSCLC (American Joint Committee on Cancer [AJCC 8th edition])
- Has measurable disease based on RECIST 1.1
- Has tumor tissue that demonstrates programmed cell death-ligand 1 (PD-L1) expression in ≥1% of tumor cells (Tumor Proportion Score [TPS] ≥1%) as assessed by immunohistochemistry (IHC) 22C3 pharmDx assay (Dako North America, Inc.) at a central laboratory
- Has a life expectancy of ≥3 months
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before the first dose of study treatment but before randomization
- Male participants must agree to the following during the treatment period and for ≥7 days after the last dose of lenvatinib/matching placebo: 1) Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR 2) Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause)
- Female participants are eligible to participate if not pregnant or breastfeeding, and ≥1 of the following applies: 1) Is not a woman of child-bearing potential (WOCBP), OR 2) Is a WOCBP and is using a highly effective contraceptive method that has a low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle during the treatment period and for ≥120 days post pembrolizumab or ≥30 days post lenvatinib/matching placebo, whichever occurs last
- Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg and no change in antihypertensive medications within 1 week before randomization
- Has adequate organ function
- Has known untreated central nervous system metastases and/or carcinomatous meningitis
- Has active hemoptysis (at least 0.5 teaspoon of bright red blood) within 2 weeks prior to the first dose of study intervention
- Has radiographic evidence of intratumoral cavitations, encasement, or invasion of a major blood vessel
- Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for ≥3 years since initiation of that therapy. (Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.)
- Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed
- Has had an allogeneic tissue/solid organ transplant
- Has a known history of human immunodeficiency virus (HIV) infection
- Has a history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease
- Has a known history of hepatitis B or known active hepatitis C virus infection
- Has a history of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral study drug absorption.
- Has significant cardiovascular impairment within 12 months of the first dose of study treatment, such as a history of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocardial infarction, cerebrovascular accident/stroke, or cardiac arrhythmia associated with hemodynamic instability
- Has not recovered adequately from any toxicity and/or complications from major surgery before starting study treatment
- Has a known history of active tuberculosis (TB)
- Has an active infection requiring systemic therapy
- Has previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity or intolerance to any component of lenvatinib or pembrolizumab
- Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Tumor necrosis factor receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor superfamily member 9 [CD137]) or has received lenvatinib as monotherapy or in combination with anti- programmed cell death protein (anti-PD-1) agents
- Has received radiotherapy within 14 days before the first dose of study treatment or received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment. (Note: Participants must have recovered from all radiation-related toxicities to ≤Grade 1, not require corticosteroids, and not have had radiation pneumonitis.)
- Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days before the first dose of study treatment
- Is receiving systemic steroid therapy (doses >10 mg daily of prednisone equivalent) within 7 days before the first dose of study treatment
- Has received a live or attenuated vaccine within 30 days before the first dose of study treatment
- Has had major surgery within 3 weeks prior to first dose of study treatment
- Has pre-existing ≥Grade 3 gastrointestinal or nongastrointestinal fistula
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab + Placebo Placebo for lenvatinib Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. Pembrolizumab + Placebo Pembrolizumab Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. Pembrolizumab + Lenvatinib Pembrolizumab Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. Pembrolizumab + Lenvatinib Lenvatinib Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Up to approximately 25 months PFS was defined as the time from date of randomization to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Data are from the product-limit (Kaplan-Meier) method for censored data. PFS as assessed by blinded independent central review (BICR) per RECIST 1.1 was presented.
Overall Survival (OS) Up to approximately 25 months OS was defined as the time from date of randomization to date of death from any cause. OS was presented.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Up to approximately 25 months ORR was defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR as assessed by BICR per RECIST 1.1 is presented.
Number of Participants Who Experienced an Adverse Event (AE) Through 90 days post last dose of study treatment (Up to approximately 27 months) An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experienced an AE were reported
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) Through last dose of study treatment (Up to approximately 24 months) An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued study treatment due to an AE were reported.
Change From Baseline in European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core30 (QLQ-C30) Combined Global Health Status/Quality of Life (Items 29 & 30) Scale Combined Score Baseline and Week 21 EORTC QLQ-C30 is a questionnaire to assess the overall quality of life (QoL) of cancer patients. Participant responses to questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and QoL ("How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) is computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. Per protocol, the change from baseline in GHS and QoL combined score was presented.
Change From Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score Baseline and Week 21 The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "How much did you cough?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. Per protocol, the change from baseline in cough (EORTC QLQ-LC13 Item 31) score was presented.
Change From Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) Score Baseline and Week 21 The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. Per protocol, the change from baseline in EORTC QLQ-LC13 chest pain (Item 40) score was presented.
Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score Baseline and Week 21 EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to the question: "Were you short of breath?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. Per protocol, the change from baseline in EORTC QLQ-C30 dyspnea (Item 8) score was presented.
Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score Baseline and Week 21 EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. Per protocol, the change from baseline in EORTC QLQ-C30 physical functioning (Items 1-5) combined score was presented.
Time to True Deterioration (TTD) in EORTC QLQ-C30 Combined Global Health Status /Quality of Life (Items 29 & 30) Scale Combined Score Up to approximately 25 months EORTC QLQ-C30 is a questionnaire to assess QoL of cancer patients. Participant responses to questions on GHS ("How would you rate your overall health during the past week?") and QoL ("How would you rate your overall QoL during the past week?") were scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) was computed by averaging raw scores of the 2 items and applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in GHS-QoL combined score. A longer TTD indicates a better outcome.
Time to True Deterioration (TTD) in EORTC QLQ-LC13 Cough (Item 31) Scale Score Up to approximately 25 months EORTC QLQ-LC13 is a lung cancer specific questionnaire. Participant responses to the question: "How much did you cough?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0-100. A lower score indicates a better outcome. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in cough (Item 31). A longer TTD indicates a better outcome.
Time to True Deterioration (TTD) in EORTC QLQ-LC13 Chest Pain (Item 40) Scale Score Up to approximately 25 months EORTC QLQ-LC13 is a lung cancer specific questionnaire. Participant responses to the question: "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0-100. A lower score indicates a better outcome. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in cough (Item 40). A longer TTD indicates a better outcome.
Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score Up to approximately 25 months EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to the question: "Were you short of breath?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in dyspnea (Item 8). A longer TTD indicates a better outcome.
Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score Up to approximately 25 months EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in physical functioning (Items 1 to 5). A longer TTD indicates a better outcome.
Time to True Deterioration (TTD) Based on Change From Baseline in the Composite Endpoint of Cough (EORTC QLQ-LC13 Item 31), Chest Pain (EORTC QLQ-LC13 Item 40), or Dyspnea (EORTC QLQ-C30 Item 8) Up to approximately 25 months The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients, including a single-item scale score for dyspnea (Item 8; score range:1=Not at All to 4=Very Much). Used in combination with QLQ-C30, the EORTC QLQ-LC13 is a supplemental lung cancer-specific module, including a single-item scale score for cough (Item 31; score range:1=Not at All to 4=Very Much ) and chest pain (Item 40, score range: 1=Not at All to 4=Very Much). The combined score of items 31, 40 and 8 was computed by averaging the raw scores of the items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. The TTD in the composite endpoint of EORTC QLQ-LC13 Item 31, EORTC QLQ-LC13 Item 40, EORTC QLQ-C30 Item 8 scale score was presented, defined as the time to first onset of a ≥10point decrease from baseline in anyone of the three scale items. A longer TTD indicates better outcome.
Trial Locations
- Locations (162)
Universita Magna Grecia ( Site 0230)
🇮🇹Catanzaro, Italy
Bnei Zion Medical Center ( Site 0227)
🇮🇱Haifa, Heifa, Israel
Sourasky Medical Center ( Site 0225)
🇮🇱Tel Aviv, Israel
Oncomedica S.A. ( Site 0372)
🇨🇴Monteria, Cordoba, Colombia
CHU Jean Minjoz ( Site 0167)
🇫🇷Besancon, Doubs, France
Centre Hospitalier de la Cote Basque ( Site 0173)
🇫🇷Bayonne, Pyrenees-Atlantiques, France
ICM Val D Auerelle ( Site 0177)
🇫🇷Montpellier, Herault, France
CHU de Grenoble - Hopital Michallon ( Site 0169)
🇫🇷La Tronche, Isere, France
Policlinico Gemelli di Roma ( Site 0237)
🇮🇹Roma, Italy
Kanagawa Cancer Center ( Site 0023)
🇯🇵Yokohama, Kanagawa, Japan
Rambam Medical Center ( Site 0223)
🇮🇱Haifa, Israel
Osaka International Cancer Institute ( Site 0019)
🇯🇵Osaka, Japan
Kanagawa Cardiovascular and Respiratory Center ( Site 0026)
🇯🇵Yokohama, Kanagawa, Japan
Soroka Medical Center ( Site 0222)
🇮🇱Beer Sheva, Israel
SMG-SNU Boramae Medical Center ( Site 0078)
🇰🇷Seoul, Korea, Republic of
Sendai Kousei Hospital ( Site 0022)
🇯🇵Sendai, Miyagi, Japan
Miyagi Cancer Center ( Site 0028)
🇯🇵Natori, Miyagi, Japan
Rabin Medical Center ( Site 0224)
🇮🇱Petah Tikva, Israel
Chungbuk National University Hospital ( Site 0079)
🇰🇷Cheongju si, Chungbuk, Korea, Republic of
Institut Curie ( Site 0166)
🇫🇷Paris, France
Seoul National University Bundang Hospital ( Site 0075)
🇰🇷Seongnam-si, Kyonggi-do, Korea, Republic of
Aichi Cancer Center Hospital ( Site 0018)
🇯🇵Nagoya, Aichi, Japan
Sheba Medical Center ( Site 0220)
🇮🇱Ramat Gan, Tel Aviv, Israel
Barzilai Medical Center ( Site 0226)
🇮🇱Ashkelon, Ḥeifā, Israel
National Hospital Organization Kinki-chuo Chest Medical Center ( Site 0027)
🇯🇵Sakai, Osaka, Japan
Kindai University Hospital ( Site 0017)
🇯🇵Osakasayama, Osaka, Japan
Juntendo University Hospital ( Site 0029)
🇯🇵Tokyo, Japan
Presidio Ospedaliero San Vincenzo ( Site 0231)
🇮🇹Taormina, Messina, Italy
Hyogo Cancer Center ( Site 0021)
🇯🇵Akashi, Hyogo, Japan
Okayama University Hospital ( Site 0020)
🇯🇵Okayama, Japan
Kurume University Hospital ( Site 0025)
🇯🇵Kurume, Fukuoka, Japan
Koo Foundation Sun Yat-Sen Cancer Center ( Site 0091)
🇨🇳Taipei, Taiwan
Necmettin Erbakan Universitesi Meram Tip Fakultesi ( Site 0321)
🇹🇷Konya, Adana, Turkey
St John of God Murdoch Medical Clinic ( Site 0001)
🇦🇺Perth, Western Australia, Australia
SA Pohja-Eesti Regionaalhaigla ( Site 0162)
🇪🇪Tallin, Harjumaa, Estonia
Institut de Cancerologie de l Ouest Centre Rene Gauducheau ( Site 0185)
🇫🇷Saint Herblain, Loire-Atlantique, France
CHU de Rouen ( Site 0174)
🇫🇷Rouen, Seine-Maritime, France
Azienda Ospedaliera S. Giovanni Addolorata-Oncologia Medica ( Site 0233)
🇮🇹Roma, Lazio, Italy
Hospital Pulau Pinang. ( Site 0065)
🇲🇾Georgetown, Pulau Pinang, Malaysia
Centro Medico Imbanaco de Cali S.A ( Site 0369)
🇨🇴Cali, Valle Del Cauca, Colombia
Semmelweis Egyetem ( Site 0210)
🇭🇺Budapest, Hungary
CHU Amiens Sud ( Site 0182)
🇫🇷Amiens, Somme, France
AS Ida-Tallinna Keskhaigla ( Site 0161)
🇪🇪Tallinn, Harjumaa, Estonia
SA Tartu Ulikooli Kliinikum ( Site 0160)
🇪🇪Tartu, Tartumaa, Estonia
Centre hospitalier Toulon Sainte-Musse ( Site 0172)
🇫🇷Toulon, Var, France
Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktatokorhaz ( Site 0202)
🇭🇺Miskolc, Borsod-Abauj-Zemplen, Hungary
Biomelab S A S ( Site 0365)
🇨🇴Barranquilla, Atlantico, Colombia
Bekes Megyei Kozponti Korhaz - Pandy Kalman Tagkorhaza ( Site 0207)
🇭🇺Gyula, Bekes, Hungary
Petz Aladar Megyei Oktato Korhaz ( Site 0213)
🇭🇺Gyor, Gyor-Moson-Sopron, Hungary
Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 0203)
🇭🇺Szolnok, Jasz-Nagykun-Szolnok, Hungary
Tudogyogyintezet Torokbalint ( Site 0205)
🇭🇺Torokbalint, Pest, Hungary
Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 0217)
🇭🇺Kaposvar, Hungary
Institut Curie - Centre Rene Huguenin ( Site 0181)
🇫🇷Saint-Cloud, Hauts-de-Seine, France
CRU Hungary KFT ( Site 0209)
🇭🇺Miskolc, Borsod-Abauj-Zemplen, Hungary
Krakowski Szpital Specjalistyczny im Jana Pawla II ( Site 0253)
🇵🇱Krakow, Malopolskie, Poland
Sarawak General Hospital ( Site 0064)
🇲🇾Kuching, Sarawak, Malaysia
Centro di Riferimento Oncologico CRO ( Site 0235)
🇮🇹Aviano, Pordenone, Italy
Institut Kanser Negara - National Cancer Institute ( Site 0063)
🇲🇾Putrajaya, Wilayah Persekutuan Putrajaya, Malaysia
Oaxaca Site Management Organization SC ( Site 0389)
🇲🇽Oaxaca, Mexico
Oregon Health Sciences University ( Site 0544)
🇺🇸Portland, Oregon, United States
Beacon Hospital Sdn Bhd ( Site 0067)
🇲🇾Petaling Jaya, Selangor, Malaysia
Azienda Ospedaliera San Giuseppe Moscati ( Site 0234)
🇮🇹Avellino, Italy
A.O. Universitaria Careggi ( Site 0236)
🇮🇹Firenze, Italy
Ospedale Santa Maria delle Croci ( Site 0232)
🇮🇹Ravenna, Italy
National Hospital Organization Kyushu Medical Center ( Site 0015)
🇯🇵Fukuoka, Japan
Kyushu University Hospital ( Site 0030)
🇯🇵Fukuoka, Japan
Toranomon Hospital ( Site 0016)
🇯🇵Tokyo, Japan
Nippon Medical School Hospital ( Site 0024)
🇯🇵Tokyo, Japan
Asan Medical Center ( Site 0076)
🇰🇷Seoul, Korea, Republic of
Scripps Cancer Center ( Site 0521)
🇺🇸La Jolla, California, United States
Alaska Clinical Research Center ( Site 0511)
🇺🇸Anchorage, Alaska, United States
CBCC Global Research, Inc. ( Site 0532)
🇺🇸Bakersfield, California, United States
Florida Hospital ( Site 0526)
🇺🇸Orlando, Florida, United States
Northwest Georgia Oncology Centers PC ( Site 0518)
🇺🇸Marietta, Georgia, United States
Illinois Cancer Care, PC ( Site 0557)
🇺🇸Peoria, Illinois, United States
Parkview Cancer Center ( Site 0542)
🇺🇸Fort Wayne, Indiana, United States
University of Kentucky School of Medicine & Hospitals ( Site 0517)
🇺🇸Lexington, Kentucky, United States
Anne Arundel Medical Center Oncology and Hematology ( Site 0514)
🇺🇸Annapolis, Maryland, United States
Munson Medical Center ( Site 0512)
🇺🇸Traverse City, Michigan, United States
University of Missouri Health Care ( Site 0555)
🇺🇸Columbia, Missouri, United States
Park Nicollet Frauenshuh Cancer Center ( Site 0554)
🇺🇸Saint Louis Park, Minnesota, United States
Samsun Medical Park Hastanesi ( Site 0320)
🇹🇷Samsun, Turkey
Billings Clinic Cancer Center ( Site 0508)
🇺🇸Billings, Montana, United States
Orange Health Services ( Site 0002)
🇦🇺Orange, New South Wales, Australia
Wollongong Private Hospital ( Site 0005)
🇦🇺Wollongong, New South Wales, Australia
The Prince Charles Hospital ( Site 0011)
🇦🇺Chermside, Queensland, Australia
Cross Cancer Institute ( Site 0400)
🇨🇦Edmonton, Alberta, Canada
Lions Gate Hospital ( Site 0407)
🇨🇦North Vancouver, British Columbia, Canada
Ballarat Oncology and Haematology Services ( Site 0008)
🇦🇺Wendouree, Victoria, Australia
William Osler Health System (Brampton Civic Hospital) ( Site 0402)
🇨🇦Brampton, Ontario, Canada
Windsor Regional Cancer Program ( Site 0404)
🇨🇦Windsor, Ontario, Canada
McGill University Health Centre ( Site 0418)
🇨🇦Montreal, Quebec, Canada
Beijing Chest Hospital Capital Medical University ( Site 0111)
🇨🇳Beijing, Anhui, China
Anhui Provincial Hospital ( Site 0108)
🇨🇳Hefei, Anhui, China
The First Affiliated Hospital of Anhui Medical University ( Site 0113)
🇨🇳Hefei, Anhui, China
Peking Union Medical College Hospital ( Site 0105)
🇨🇳Beijing, Beijing, China
Beijing Cancer Hospital ( Site 0102)
🇨🇳Beijing, Beijing, China
Hunan Cancer Hospital ( Site 0104)
🇨🇳Changsha, Hunan, China
Xiangya Hospital of Central South University ( Site 0115)
🇨🇳Changsha, Hunan, China
The First Hospital of Jilin University ( Site 0110)
🇨🇳Chang chun, Jilin, China
Jiangsu Cancer Hospital ( Site 0101)
🇨🇳Nanjing, Jiangsu, China
Zhongshan Hospital Fudan University ( Site 0100)
🇨🇳Shanghai, Shanghai, China
Abdurrahman Yurtaslan Onkoloji Hastanesi ( Site 0318)
🇹🇷Ankara, Turkey
Shanghai Chest Hospital ( Site 0112)
🇨🇳Shanghai, Shanghai, China
1st Affil Hosp of Med College of Xi'an Jiaotong University ( Site 0103)
🇨🇳XiAn, Shanxi, China
West China Hospital of Sichuan University ( Site 0117)
🇨🇳Chengdu, Sichuan, China
Hangzhou First People's Hospital ( Site 0109)
🇨🇳Hangzhou, Zhejiang, China
Zhejiang Cancer Hospital ( Site 0116)
🇨🇳Hangzhou, Zhejiang, China
The First Affiliated Hospital Zhejiang University ( Site 0106)
🇨🇳Hangzhou, Zhejiang, China
2nd Affil Hosp of Zhejiang University College of Medicine ( Site 0114)
🇨🇳Hangzhou, Zhejiang, China
Hospital General de Medellin Luz Castro de Gutierrez ( Site 0368)
🇨🇴Medellin, Antioquia, Colombia
Fundacion Centro de Investigacion Clinica CIC ( Site 0366)
🇨🇴Medellin, Antioquia, Colombia
Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 0374)
🇨🇴Valledupar, Cesar, Colombia
Sakarya Universitesi Egitim ve Arastirma Hastanesi ( Site 0323)
🇹🇷Sakarya, Turkey
Ulsan University Hospital ( Site 0077)
🇰🇷Ulsan, Ulsan-Kwangyokshi, Korea, Republic of
Hospital Tengku Ampuan Afzan ( Site 0062)
🇲🇾Kuantan, Pahang, Malaysia
University Malaya Medical Centre ( Site 0061)
🇲🇾Kuala Lumpur, Malaysia
Gleneagles Penang ( Site 0066)
🇲🇾Pulau Pinang, Malaysia
Medica Sur S.A.B de C.V. ( Site 0384)
🇲🇽Mexico City, Distrito Federal, Mexico
Centro de Estudios de Investigacion Metabolicos y Cardiovasculares ( Site 0381)
🇲🇽Madero, Tamaulipas, Mexico
Szpital Uniwersytecki im. Karola Marcinkowskiego ( Site 0247)
🇵🇱Zielona Gora, Lubuskie, Poland
SPZOZ USK nr 1 im. Norberta Barlickiego UM w Lodzi ( Site 0256)
🇵🇱Lodz, Lodzkie, Poland
Instituto Nacional de Cancerologia. ( Site 0382)
🇲🇽Mexico City, Mexico
Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie ( Site 0243)
🇵🇱Krakow, Malopolskie, Poland
Centrum Medyczne Pratia Ostroleka ( Site 0242)
🇵🇱Ostroleka, Mazowieckie, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0252)
🇵🇱Warszawa, Mazowieckie, Poland
Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 0250)
🇵🇱Przemysl, Podkarpackie, Poland
Ars Medical Sp. z o.o. ( Site 0254)
🇵🇱Pila, Wielkopolskie, Poland
SBHI Samara Regional Clinical Oncology Dispensary ( Site 0265)
🇷🇺Samara, Samarskaya Oblast, Russian Federation
SBHI Leningrad Regional Clinical Hospital ( Site 0263)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 0262)
🇷🇺Ufa, Baskortostan, Respublika, Russian Federation
Railway Hospital of OJSC ( Site 0268)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0266)
🇷🇺Krasnoyarsk, Krasnoyarskiy Kray, Russian Federation
City Clinical Oncology Center ( Site 0260)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 0269)
🇷🇺Kazan, Tatarstan, Respublika, Russian Federation
Taipei Medical University Shuang Ho Hospital ( Site 0090)
🇨🇳New Taipei, Taiwan
National Taiwan University Hospital Hsin-Chu Branch ( Site 0087)
🇨🇳Hsinchu, Taiwan
National Cheng Kung University Hospital ( Site 0086)
🇨🇳Tainan, Taiwan
Taipei Veterans General Hospital ( Site 0089)
🇨🇳Taipei, Taiwan
National Taiwan University Hospital ( Site 0088)
🇨🇳Taipei, Taiwan
Gulhane Egitim ve Arastirma Hastanesi ( Site 0316)
🇹🇷Ankara, Turkey
Baskent Universitesi Ankara Hastanesi ( Site 0319)
🇹🇷Ankara, Turkey
Akdeniz Universitesi Tip Fakultesi ( Site 0322)
🇹🇷Antalya, Turkey
Dokuz Eylul Universitesi Arastirma Uygulama Hastanesi ( Site 0314)
🇹🇷Izmir, Turkey
Antalya Memorial Hospital Department of Medical Oncology ( Site 0324)
🇹🇷Antalya, Turkey
Cherkasy Regional Hospital ( Site 0336)
🇺🇦Cherkasy, Cherkaska Oblast, Ukraine
City Clinical Hosp.4 of DCC ( Site 0338)
🇺🇦Dnipro, Dnipropetrovska Oblast, Ukraine
MI Precarpathian Clinical Oncology Center ( Site 0346)
🇺🇦Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine
Regional Centre of Oncology-Thoracic organs ( Site 0337)
🇺🇦Kharkiv, Kharkivska Oblast, Ukraine
Ukranian Center of TomoTherapy ( Site 0344)
🇺🇦Kropyvnytskiy, Kirovohradska Oblast, Ukraine
Medical Center Verum ( Site 0334)
🇺🇦Kyiv, Kyivska Oblast, Ukraine
Lviv State Oncology Regional Treatment and Diagnostic Center ( Site 0341)
🇺🇦Lviv, Lvivska Oblast, Ukraine
Kyiv City Clinical Oncology Centre ( Site 0339)
🇺🇦Kyiv, Kyivska Oblast, Ukraine
Medical and Diagnostic Centre LLC Dobryi Prognoz ( Site 0331)
🇺🇦Kyiv, Kyivska Oblast, Ukraine
MI Odessa Regional Oncological Centre ( Site 0333)
🇺🇦Odesa, Odeska Oblast, Ukraine
Podillya Regional Center of Oncology ( Site 0343)
🇺🇦Vinnytsia, Vinnytska Oblast, Ukraine
Central Texas Veterans Healthcare System ( Site 0533)
🇺🇸Temple, Texas, United States
Meir Medical Center ( Site 0221)
🇮🇱Kfar-Saba, Israel
Cone Health Cancer Center at Alamance Regional ( Site 0527)
🇺🇸Greensboro, North Carolina, United States
Ironwood Cancer & Research Centers ( Site 0541)
🇺🇸Chandler, Arizona, United States
Genesis Cancer Care Center ( Site 0559)
🇺🇸Zanesville, Ohio, United States
Consultorios de Medicina Especializada del Sector Privado ( Site 0388)
🇲🇽Guadalajara, Jalisco, Mexico