MedPath

Placebo-controlled, Study of Concurrent Chemoradiation Therapy With Pembrolizumab Followed by Pembrolizumab and Olaparib in Newly Diagnosed Treatment-Naïve Limited-Stage Small Cell Lung Cancer (LS-SCLC) (MK 7339-013/KEYLYNK-013)

Phase 3
Active, not recruiting
Conditions
Small Cell Lung Cancer
Interventions
Drug: Platinum, investigator's choice
Radiation: Standard Thoracic Radiotherapy
Radiation: Prophylactic Cranial Irradiation (PCI)
Registration Number
NCT04624204
Lead Sponsor
Merck Sharp & Dohme LLC
Brief Summary

Researchers are looking for new ways to treat Limited-Stage Small Cell Lung Cancer (LS-SCLC), a type of lung cancer that has not spread from the lung to other parts of the body. The purpose of this study is to learn if pembrolizumab and olaparib, when given with chemotherapy and radiation treatment (CRT), can be effective in treating LS-SCLC. The researchers want to know if participants who receive CRT and pembrolizumab, with or without olaparib, have a longer overall survival compared to participants who only receive CRT.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
672
Inclusion Criteria
  1. Has pathologically (histologically or cytologically) confirmed Small Cell Lung Cancer (SCLC).

    Note: Note: Participants with histology showing a mixed tumor with small cell and non-small cell elements are not eligible.

  2. Has Limited-Stage SCLC (Stage I-III, by AJCC 8th Edition Cancer Staging), and can be safely treated with definitive radiation doses.

  3. Has no evidence of metastatic disease by whole body positron emission tomography /computed tomography (PET/CT scan), CT or magnetic resonance imaging (MRI) scans

  4. Has at least 1 lesion that meets the criteria for being measurable, as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)

  5. Has not received prior treatment (chemotherapy or radiotherapy or surgery resection) of LS-SCLC.

  6. Is not expected to require tumor resection during the course of the study.

  7. Must submit a pre-treatment tumor tissue sample (formalin-fixed, paraffin embedded blocks are preferred to slides) including cytologic sample, if tissue sample unavailable.

  8. Has Eastern Cooperative Oncology Group (ECOG) Performance score 0 or 1 assessed within 7 days prior to the first administration of study intervention.

  9. Has a life expectancy of at least 6 months.

  10. Has adequate organ function.

  11. Male and female participants who are not pregnant and of childbearing potential must follow contraceptive guidance during the treatment period and for the time needed to eliminate each study intervention.

  12. Male and female participants who are at least 18 years of age at the time of signing the information consent.

  13. Male participants must refrain from donating sperm during the treatment period and for the time needed to eliminate each study intervention.

  14. Abstains from breastfeeding during the study intervention period and for at least the following period after the last study intervention:

    • Pembrolizumab: 120 days
    • Olaparib: 7 days
Exclusion Criteria
  1. Has history, current diagnosis, or features suggestive of myelodysplastic syndrome/ acute myeloid leukemia (MDS/AML).
  2. Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PDL1), or anti- programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
  3. Has received prior therapy with olaparib or with any other polyadenosine 5'diphosphoribose (polyADP ribose) polymerization (PARP) inhibitor.
  4. Had major surgery <4 weeks prior to the first dose of study intervention (except for placement of vascular access).
  5. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
  6. 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 the first dose of study intervention.
  7. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  8. Has severe hypersensitivity (≥ Grade 3) to study intervention and/or any of its excipients.
  9. Has an active autoimmune disease that has required systemic treatment in past 2 years
  10. Has a history of (non-infectious) pneumonitis/interstitial lung disease that requires steroids
  11. Has an active infection requiring systemic therapy.
  12. Has a known history of human immunodeficiency virus (HIV) infection or Hepatitis B or known active Hepatitis C virus infection.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group A - Pembrolizumab 200 mgPembrolizumab 200 mgParticipants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab 200 mg every 3 weeks (Q3W) concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab 400 mg every 6 weeks (Q6W) plus olaparib matching placebo twice daily (BID) for 12 months or until specific discontinuation criteria are met.
Group A - Pembrolizumab 200 mgPembrolizumab 400 mgParticipants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab 200 mg every 3 weeks (Q3W) concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab 400 mg every 6 weeks (Q6W) plus olaparib matching placebo twice daily (BID) for 12 months or until specific discontinuation criteria are met.
Group B - Pembrolizumab 200 mg plus Olaparib 300 mg BIDPembrolizumab 400 mgParticipants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab 200 mg Q3W concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab 400 mg Q6W plus olaparib 300 mg BID for 12 months or until specific discontinuation criteria are met.
Group B - Pembrolizumab 200 mg plus Olaparib 300 mg BIDEtoposide 100 mg/m^2Participants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab 200 mg Q3W concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab 400 mg Q6W plus olaparib 300 mg BID for 12 months or until specific discontinuation criteria are met.
Group C (Pembrolizumab and Olaparib Matching Placebos)Pembrolizumab placebo (saline)Participants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab placebo (saline) Q3W concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab placebo (saline) Q6W plus olaparib matching placebo for 12 months or until specific discontinuation criteria are met.
Group C (Pembrolizumab and Olaparib Matching Placebos)Etoposide 100 mg/m^2Participants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab placebo (saline) Q3W concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab placebo (saline) Q6W plus olaparib matching placebo for 12 months or until specific discontinuation criteria are met.
Group B - Pembrolizumab 200 mg plus Olaparib 300 mg BIDOlaparib 300 mg BIDParticipants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab 200 mg Q3W concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab 400 mg Q6W plus olaparib 300 mg BID for 12 months or until specific discontinuation criteria are met.
Group A - Pembrolizumab 200 mgOlaparib matching placeboParticipants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab 200 mg every 3 weeks (Q3W) concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab 400 mg every 6 weeks (Q6W) plus olaparib matching placebo twice daily (BID) for 12 months or until specific discontinuation criteria are met.
Group A - Pembrolizumab 200 mgStandard Thoracic RadiotherapyParticipants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab 200 mg every 3 weeks (Q3W) concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab 400 mg every 6 weeks (Q6W) plus olaparib matching placebo twice daily (BID) for 12 months or until specific discontinuation criteria are met.
Group B - Pembrolizumab 200 mg plus Olaparib 300 mg BIDStandard Thoracic RadiotherapyParticipants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab 200 mg Q3W concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab 400 mg Q6W plus olaparib 300 mg BID for 12 months or until specific discontinuation criteria are met.
Group A - Pembrolizumab 200 mgEtoposide 100 mg/m^2Participants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab 200 mg every 3 weeks (Q3W) concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab 400 mg every 6 weeks (Q6W) plus olaparib matching placebo twice daily (BID) for 12 months or until specific discontinuation criteria are met.
Group A - Pembrolizumab 200 mgPlatinum, investigator's choiceParticipants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab 200 mg every 3 weeks (Q3W) concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab 400 mg every 6 weeks (Q6W) plus olaparib matching placebo twice daily (BID) for 12 months or until specific discontinuation criteria are met.
Group A - Pembrolizumab 200 mgProphylactic Cranial Irradiation (PCI)Participants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab 200 mg every 3 weeks (Q3W) concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab 400 mg every 6 weeks (Q6W) plus olaparib matching placebo twice daily (BID) for 12 months or until specific discontinuation criteria are met.
Group B - Pembrolizumab 200 mg plus Olaparib 300 mg BIDPembrolizumab 200 mgParticipants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab 200 mg Q3W concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab 400 mg Q6W plus olaparib 300 mg BID for 12 months or until specific discontinuation criteria are met.
Group B - Pembrolizumab 200 mg plus Olaparib 300 mg BIDPlatinum, investigator's choiceParticipants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab 200 mg Q3W concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab 400 mg Q6W plus olaparib 300 mg BID for 12 months or until specific discontinuation criteria are met.
Group B - Pembrolizumab 200 mg plus Olaparib 300 mg BIDProphylactic Cranial Irradiation (PCI)Participants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab 200 mg Q3W concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab 400 mg Q6W plus olaparib 300 mg BID for 12 months or until specific discontinuation criteria are met.
Group C (Pembrolizumab and Olaparib Matching Placebos)Olaparib matching placeboParticipants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab placebo (saline) Q3W concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab placebo (saline) Q6W plus olaparib matching placebo for 12 months or until specific discontinuation criteria are met.
Group C (Pembrolizumab and Olaparib Matching Placebos)Platinum, investigator's choiceParticipants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab placebo (saline) Q3W concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab placebo (saline) Q6W plus olaparib matching placebo for 12 months or until specific discontinuation criteria are met.
Group C (Pembrolizumab and Olaparib Matching Placebos)Standard Thoracic RadiotherapyParticipants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab placebo (saline) Q3W concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab placebo (saline) Q6W plus olaparib matching placebo for 12 months or until specific discontinuation criteria are met.
Group C (Pembrolizumab and Olaparib Matching Placebos)Prophylactic Cranial Irradiation (PCI)Participants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab placebo (saline) Q3W concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab placebo (saline) Q6W plus olaparib matching placebo for 12 months or until specific discontinuation criteria are met.
Primary Outcome Measures
NameTimeMethod
Progression-free Survival Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1); the time from randomization to progression or death due to any cause, whichever occurs firstUp to approximately 59 months

Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) is the time from randomization to progression or death due to any cause, whichever occurs first.

Overall Survival: the time from randomization to death due to any causeUp to approximately 82 months

Overall Survival (OS) is the time from randomization to death due to any cause.

Secondary Outcome Measures
NameTimeMethod
Objective Response (OR): Complete Response (CR) or Partial Response (PR)Up to approximately 82 months

Percentage of participants in the analysis population who have a best overall response of either confirmed CR or a PR per RECIST 1.1.

Time to True Deterioration (TTD) in Chest Pain (LC13/Item 10) Scale ScoreUp to approximately 82 months post randomization

The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQC30 questionnaire. Participant responses to the question "How was your chest pain?" 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 (at randomization) to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in EORTC QLQ-LC13 chest pain (Item 10) scale score.

Time to True Deterioration (TTD) in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale ScoreUp to approximately 82 months post randomization

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning 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 higher score indicates a better quality of life. TTD was defined as the time from baseline (at randomization) to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in EORTC QLQ-C30 physical functioning (Items 1 to 5) scale scores.

Number of Participants Experiencing an Adverse Events (AEs)Up to approximately 82 months

An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Number of Participants Discontinuing Study Treatment Due to Adverse Events (AEs)Up to approximately 82 months

An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Change from Baseline at Cycle 1 in European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status / Quality of Life (Items 29 & 30) Scale ScoreBaseline and 82 months post randomization

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "How would you rate your overall health during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 scores will be presented.

Duration of Response (DOR): the time from the earliest date of first documented evidence of confirmed CR or PR until the earliest date of disease progression or death from any cause, whichever comes firstUp to approximately 82 months

DOR is the time from the earliest date of first documented evidence of confirmed CR or PR until the earliest date of disease progression or death from any cause, whichever comes first.

Change from Baseline at Cycle 1 in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale ScoreBaseline and 82 months post randomization

The EORTC QLQ-LC13 is a lung cancer specific supplemental questionnaire used in combination with the EORTC QLQC30 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 to 100. A lower score indicates a better outcome. The change from baseline in EORTC QLQ-LC13 cough (Item 1) score will be presented.

Change from Baseline at Cycle 1 in EORTC QLQ-LC13 Chest Pain (Item 10) Scale ScoreBaseline and 82 months post randomization

The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQC30 questionnaire. Participant responses to the question "How was your chest pain?" 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. The change from baseline in EORTC QLQ-LC13 chest pain (Item 10) score will be presented.

Change from Baseline at Cycle 1 in EORTC QLQ-C30 Dyspnea (Item 8) Scale ScoreBaseline and 82 months post randomization

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life 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. The change from baseline in EORTC QLQ-LC13 dyspnea (Item 8) score will be presented.

Change from Baseline at Cycle 1 in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale ScoreBaseline and 82 months post randomization

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning 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 higher score indicates a better quality of life. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) score will be presented.

Time to True Deterioration (TTD) in EORTC QLQ-C30 Global Health Status / Quality of Life (Items 29 & 30) Scale ScoreUp to approximately 82 months post randomization

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "How would you rate your overall health during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. TTD was defined as the time from baseline (at randomization) to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in EORTC QLQ-C30 Items 29 and 30 scale scores.

Time to True Deterioration (TTD) in Cough (LC13/Item 1) Scale ScoreUp to approximately 82 months post randomization

The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQC30 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 to 100. A lower score indicates a better outcome. TTD was defined as the time from baseline (at randomization) to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in cough EORTC QLQLC13 cough (Item 1) scale score.

Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale ScoreUp to approximately 82 months post randomization

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life 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 (at randomization) to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in EORTC QLQ-C30 dyspnea (Item 8) scale score.

Progression-free Survival (PFS, according to RECIST 1.1 by BICR) assessed by programmed cell death ligand 1 (PD-L1) expression levelsUp to approximately 59 months

Progression-free Survival Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1); the time from randomization to progression or death due to any cause, whichever occurs first, analyzed by programmed cell death ligand 1 (PD-L1) expression levels.

Overall Survival (OS) assessed by programmed cell death ligand 1 (PD-L1) expression levelsUp to approximately 82 months

Overall Survival: the time from randomization to death due to any cause, analyzed by programmed cell death ligand 1 (PD-L1) expression levels.

Objective Response (OR, according to RECIST 1.1 by BICR) assessed by programmed cell death ligand 1 (PD-L1) expression levelsUp to approximately 82 months

Percentage of participants in the analysis population who have a best overall response of either confirmed CR or a PR per RECIST 1.1, analyzed by programmed cell death ligand 1 (PD-L1) expression levels.

Duration of Response (DOR, according to RECIST 1.1 by BICR) assessed by programmed cell death ligand 1 (PD-L1) expression levelsUp to approximately 82 months

DOR is the time from the earliest date of first documented evidence of confirmed CR or PR until the earliest date of disease progression or death from any cause, whichever comes first, analyzed by programmed cell death ligand 1 (PD-L1) expression levels.

Trial Locations

Locations (188)

Fairview Hospital-Moll Cancer Center ( Site 0141)

🇺🇸

Cleveland, Ohio, United States

Cleveland Clinic Main ( Site 0139)

🇺🇸

Cleveland, Ohio, United States

MD Anderson Cancer Center ( Site 0100)

🇺🇸

Houston, Texas, United States

Millennium Research & Clinical Development ( Site 0143)

🇺🇸

Houston, Texas, United States

CHU UCL Namur Site de Godinne ( Site 1004)

🇧🇪

Yvoir, Namur, Belgium

Nacionalinis Vezio Institutas ( Site 2300)

🇱🇹

Vilnius, Vilniaus Miestas, Lithuania

Centro Hospitalar Lisboa Norte E.P.E. - Hospital Pulido Valente ( Site 1704)

🇵🇹

Lisboa, Portugal

Amethyst Radiotherapy Center-Oncologie Medicala ( Site 2805)

🇷🇴

Florești, Cluj, Romania

Communal Noncommercial Enterprise "Podillia Regional Oncolog-Chemotherapy Department ( Site 2114)

🇺🇦

Vinnytsia, Vinnytska Oblast, Ukraine

Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 2803)

🇷🇴

Cluj-Napoca, Cluj, Romania

Taunton and Somerset Hospital ( Site 2404)

🇬🇧

Taunton, England, United Kingdom

Grand Hopital de Charleroi ( Site 1003)

🇧🇪

Charleroi, Hainaut, Belgium

C.I.U. Hopital Ambroise Pare ( Site 1001)

🇧🇪

Mons, Hainaut, Belgium

SA Tartu Ulikooli Kliinikum ( Site 2200)

🇪🇪

Tartu, Tartumaa, Estonia

Institute for Oncology and Radiology of Serbia ( Site 2995)

🇷🇸

Belgrade, Beograd, Serbia

Hospital Universitario "Dr. Jose Eleuterio Gonzalez" ( Site 0404)

🇲🇽

Monterrey, Nuevo Leon, Mexico

Medical Center Verum ( Site 2106)

🇺🇦

Kyiv, Kyivska Oblast, Ukraine

Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0401)

🇲🇽

Guadalajara, Jalisco, Mexico

Medical center Medikal Plaza of Ecodnipro LLC ( Site 2107)

🇺🇦

Dnipro, Dnipropetrovska Oblast, Ukraine

Municipal non-profit Enterprise "Khmelnytskyi Regional Antitumor Center" ( Site 2115)

🇺🇦

Khmelnytskyi, Khmelnytska Oblast, Ukraine

Uzsoki Utcai Korhaz ( Site 1303)

🇭🇺

Budapest, Hungary

Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 1306)

🇭🇺

Kecskemét, Bacs-Kiskun, Hungary

Ironwood Cancer & Research Centers ( Site 0007)

🇺🇸

Chandler, Arizona, United States

Georgetown University ( Site 0017)

🇺🇸

Washington, District of Columbia, United States

University of Chicago Medical Center ( Site 0136)

🇺🇸

Chicago, Illinois, United States

Fort Wayne Medical Oncology and Hematology ( Site 0034)

🇺🇸

Fort Wayne, Indiana, United States

University of Kentucky Chandler Medical Center ( Site 0138)

🇺🇸

Lexington, Kentucky, United States

Harry & Jeanette Weinberg Cancer Institute ( Site 0045)

🇺🇸

Baltimore, Maryland, United States

Overton Brooks VAMC ( Site 0041)

🇺🇸

Shreveport, Louisiana, United States

Memorial Sloan Kettering - Basking Ridge ( Site 0133)

🇺🇸

Basking Ridge, New Jersey, United States

St. Vincent Healthcare Frontier Cancer Center ( Site 0056)

🇺🇸

Billings, Montana, United States

Memorial Sloan Kettering - Bergen ( Site 0130)

🇺🇸

Montvale, New Jersey, United States

Rutgers Cancer Institute of New Jersey ( Site 0123)

🇺🇸

New Brunswick, New Jersey, United States

Memorial Sloan Kettering - Westchester-Thoracic Oncology ( Site 0134)

🇺🇸

Harrison, New York, United States

Cleveland Clinic - Hillcrest Hospital-Hillcrest Hospital Cancer Center ( Site 0140)

🇺🇸

Mayfield Heights, Ohio, United States

Penn State Hershey Cancer Institute ( Site 0081)

🇺🇸

Hershey, Pennsylvania, United States

Saint Francis Cancer Center ( Site 0087)

🇺🇸

Greenville, South Carolina, United States

The University of Tennessee Medical Center ( Site 0116)

🇺🇸

Knoxville, Tennessee, United States

Texas Oncology - Dallas (Presbyterian)_McIntyre ( Site 0098)

🇺🇸

Dallas, Texas, United States

Texas Oncology - Dallas (Sammons) ( Site 0093)

🇺🇸

Dallas, Texas, United States

Providence Regional Cancer Partnership ( Site 0106)

🇺🇸

Everett, Washington, United States

Medical Oncology Associates, PS ( Site 0142)

🇺🇸

Spokane, Washington, United States

Virginia Mason Memorial- North Star Lodge Cancer Center ( Site 0112)

🇺🇸

Yakima, Washington, United States

Nepean Hospital ( Site 3001)

🇦🇺

Kingswood, New South Wales, Australia

Calvary Mater Newcastle ( Site 3000)

🇦🇺

Waratah, New South Wales, Australia

Gold Coast University Hospital ( Site 3003)

🇦🇺

Southport, Queensland, Australia

Frankston Hospital-Oncology and Haematology ( Site 3007)

🇦🇺

Frankston, Victoria, Australia

Austin Health-Austin Hospital ( Site 3006)

🇦🇺

Heidelberg, Victoria, Australia

Western Health-Sunshine Hospital ( Site 3004)

🇦🇺

St Albans, Victoria, Australia

Saint-Luc UCL ( Site 1005)

🇧🇪

Brussels, Bruxelles-Capitale, Region De, Belgium

UZ Leuven ( Site 1002)

🇧🇪

Leuven, Vlaams-Brabant, Belgium

Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0212)

🇨🇦

Hamilton, Ontario, Canada

Cross Cancer Institute ( Site 0206)

🇨🇦

Edmonton, Alberta, Canada

CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0202)

🇨🇦

Montreal, Quebec, Canada

AZ Delta ( Site 1000)

🇧🇪

Roeselare, West-Vlaanderen, Belgium

MHAT "Uni Hospital" OOD ( Site 2507)

🇧🇬

Panagyurishte, Pazardzhik, Bulgaria

McGill University Health Centre ( Site 0210)

🇨🇦

Montréal, Quebec, Canada

Cancer Hospital Chinese Academy of Medical Sciences ( Site 3104)

🇨🇳

Beijing, Beijing, China

CIUSSS de la Mauricie et du Centre du Quebec ( Site 0200)

🇨🇦

Trois-Rivieres, Quebec, Canada

Peking Union Medical College Hospital ( Site 3102)

🇨🇳

Beijing, Beijing, China

Beijing Cancer Hospital ( Site 3127)

🇨🇳

Beijing, Beijing, China

Beijing Cancer hospital-Oncology Radiotherapy Department ( Site 3140)

🇨🇳

Beijing, Beijing, China

Chongqing Cancer Hospital ( Site 3135)

🇨🇳

Chongqing, Chongqing, China

Daping Hospital,Third Military Medical University ( Site 3136)

🇨🇳

Chongqing, Chongqing, China

Fujian Provincial Cancer Hospital ( Site 3126)

🇨🇳

Fuzhou, Fujian, China

The First Affiliated Hospital of Xiamen University ( Site 3121)

🇨🇳

Xiamen, Fujian, China

Peking University Shenzhen Hospital ( Site 3118)

🇨🇳

Shenzhen, Guangdong, China

Henan Cancer Hospital ( Site 3105)

🇨🇳

Zhengzhou, Henan, China

Wuhan Union Hospital ( Site 3123)

🇨🇳

Wuhan, Hubei, China

Tongji Medical College Huazhong University of Science and Technology ( Site 3138)

🇨🇳

Wuhan, Hubei, China

Hunan Cancer Hospital ( Site 3133)

🇨🇳

Changsha, Hunan, China

Hubei Cancer Hospital ( Site 3120)

🇨🇳

Wuhan, Hubei, China

Xiangya Hospital of Central South University ( Site 3137)

🇨🇳

Changsha, Hunan, China

The First Hospital of Jilin University ( Site 3132)

🇨🇳

Changchun, Jilin, China

The Second Affiliated Hospital of Nanchang University ( Site 3106)

🇨🇳

Nanchang, Jiangxi, China

Jiangsu Cancer Hospital ( Site 3139)

🇨🇳

Nanjing, Jiangsu, China

Shandong Province Cancer Hospital ( Site 3100)

🇨🇳

Jinan, Shandong, China

Shanghai Chest Hospital ( Site 3107)

🇨🇳

Shangai, Shanghai, China

West China Hospital of Sichuan University ( Site 3114)

🇨🇳

Chengdu, Sichuan, China

Shanghai Pulmonary Hospital ( Site 3101)

🇨🇳

Shanghai, Shanghai, China

Tianjin Medical University Cancer Institute & Hospital ( Site 3103)

🇨🇳

Tianjin, Tianjin, China

Hangzhou Cancer Hospital ( Site 3129)

🇨🇳

Hanghzou, Zhejiang, China

The 1st Affil Hosp of College of Medicine, Zhejiang Univ ( Site 3131)

🇨🇳

Hangzhou, Zhejiang, China

SA Pohja-Eesti Regionaalhaigla ( Site 2201)

🇪🇪

Tallinn, Harjumaa, Estonia

Clinique Clairval ( Site 1108)

🇫🇷

Marseille, Bouches-du-Rhone, France

Institut De Cancerologie De L Ouest ( Site 1110)

🇫🇷

Saint Herblain, Loire-Atlantique, France

Hopital Avicenne ( Site 1106)

🇫🇷

Bobigny, Seine-Saint-Denis, France

Institut de Cancerologie de l Ouest Site Paul Papin ( Site 1103)

🇫🇷

Angers, Maine-et-Loire, France

H.I.A. Sainte-Anne ( Site 1101)

🇫🇷

Toulon, Var, France

Henry Dunant Hospital ( Site 1205)

🇬🇷

Athens, Attiki, Greece

Orszagos Onkologiai Intezet ( Site 1310)

🇭🇺

Budapest, Hungary

Anti-Cancer Hospital of Thessaloniki Theagenio ( Site 1204)

🇬🇷

Thessaloniki, Kentriki Makedonia, Greece

Petz Aladar Megyei Oktato Korhaz ( Site 1312)

🇭🇺

Gyor, Gyor-Moson-Sopron, Hungary

University General Hospital of Larisa ( Site 1201)

🇬🇷

Larissa, Thessalia, Greece

Orszagos Koranyi Pulmonologiai Intezet ( Site 1301)

🇭🇺

Budapest, Hungary

Rambam Health Care Campus-Oncology Division ( Site 1401)

🇮🇱

Haifa, Israel

Chaim Sheba Medical Center ( Site 1400)

🇮🇱

Ramat Gan, Israel

Azienda Ospedaliera Spedali Civili di Brescia ( Site 1512)

🇮🇹

Brescia, Italy

A O U Policlinico di Modena ( Site 1503)

🇮🇹

Modena, Emilia-Romagna, Italy

Azienda Ospedaliero Universitaria Careggi ( Site 1509)

🇮🇹

Florence, Firenze, Italy

Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Trento-Oncology Unit ( Site 1513

🇮🇹

Verona, Veneto, Italy

IRCCS Ospedale San Raffaele ( Site 1500)

🇮🇹

Milano, Italy

Istituto Nazionale dei Tumori ( Site 1504)

🇮🇹

Milano, Italy

IRCCS Istituto Oncologico Veneto ( Site 1506)

🇮🇹

Padova, Italy

Istituto Europeo di Oncologia ( Site 1501)

🇮🇹

Milano, Italy

Policlinico Universitario Agostino Gemelli ( Site 1505)

🇮🇹

Roma, Italy

Aichi Cancer Center Hospital ( Site 4010)

🇯🇵

Nagoya, Aichi, Japan

Kobe Minimally Invasive Cancer Center ( Site 4003)

🇯🇵

Kobe, Hyogo, Japan

Kansai Medical University Hospital ( Site 4009)

🇯🇵

Hirakata, Osaka, Japan

Kanagawa Cancer Center ( Site 4001)

🇯🇵

Yokohama, Kanagawa, Japan

Osaka Medical and Pharmaceutical University Hospital ( Site 4007)

🇯🇵

Takatsuki, Osaka, Japan

National Hospital Organization Kyushu Cancer Center ( Site 4000)

🇯🇵

Fukuoka, Japan

Okayama University Hospital ( Site 4012)

🇯🇵

Okayama, Japan

Shizuoka Cancer Center ( Site 4014)

🇯🇵

Nagaizumi, Shizuoka, Japan

Niigata Cancer Center Hospital ( Site 4004)

🇯🇵

Niigata, Japan

Juntendo University Hospital ( Site 4008)

🇯🇵

Tokyo, Japan

Osaka International Cancer Institute ( Site 4005)

🇯🇵

Osaka, Japan

Tokyo Metropolitan Komagome Hospital ( Site 4011)

🇯🇵

Tokyo, Japan

The Cancer Institute Hospital of JFCR ( Site 4006)

🇯🇵

Tokyo, Japan

Showa University Hospital ( Site 4002)

🇯🇵

Tokyo, Japan

The Catholic University of Korea St. Vincent s Hospital ( Site 3303)

🇰🇷

Suwon-si, Kyonggi-do, Korea, Republic of

National Cancer Center ( Site 3306)

🇰🇷

Goyang-si, Kyonggi-do, Korea, Republic of

Keimyung University Dongsan Hospital CRC room 1 ( Site 3302)

🇰🇷

Daegu, Taegu-Kwangyokshi, Korea, Republic of

Seoul National University Bundang Hospital ( Site 3301)

🇰🇷

Seongnam-si, Kyonggi-do, Korea, Republic of

LSMUL Kauno Klinikos ( Site 2301)

🇱🇹

Kaunas, Lithuania

Samsung Medical Center ( Site 3300)

🇰🇷

Seoul, Korea, Republic of

Severance Hospital Yonsei University Health System ( Site 3304)

🇰🇷

Seoul, Korea, Republic of

Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE ( Site 1705)

🇵🇹

Lisboa, Portugal

Spitalul Municipal Ploiesti ( Site 2801)

🇷🇴

Ploiesti, Prahova, Romania

Moscow Regional Oncological Dispensary-Oncology (thoracic surgery) Department №1 ( Site 1815)

🇷🇺

Balashikha, Moskovskaya Oblast, Russian Federation

S.C.Focus Lab Plus S.R.L ( Site 2804)

🇷🇴

Bucuresti, Romania

Cabinet Medical Oncomed ( Site 2802)

🇷🇴

Timisoara, Timis, Romania

Nizhniy Novgorod Region Oncology Dispensary ( Site 1811)

🇷🇺

Nizhny Novgorod, Nizhegorodskaya Oblast, Russian Federation

MROI n.a. P.A. Herzen - branch of FSBI NMICR of MoH of Russia ( Site 1800)

🇷🇺

Moscow, Moskva, Russian Federation

Omsk Clinical Oncology Dispensary ( Site 1806)

🇷🇺

Omsk, Omskaya Oblast, Russian Federation

Sverdlovsk Regional Oncology Hospital ( Site 1807)

🇷🇺

Ekaterinburg, Sverdlovskaya Oblast, Russian Federation

Republican Clinical Oncology Dispensary-Chemotherapy #1 ( Site 1814)

🇷🇺

Kazan, Tatarstan, Respublika, Russian Federation

Groote Schuur Hospital ( Site 5002)

🇿🇦

Cape Town, Western Cape, South Africa

Institut za plucne bolesti Vojvodine Sremska Kamenica ( Site 2991)

🇷🇸

Sremska Kamenica, Sremski Okrug, Serbia

Steve Biko Academic Hospital ( Site 5000)

🇿🇦

Pretoria, Gauteng, South Africa

Hospital Duran i Reynals ( Site 1903)

🇪🇸

Hospitalet de Llobregat, Barcelona, Spain

Hospital Universitari Vall d Hebron ( Site 1904)

🇪🇸

Barcelona, Spain

Hospital Universitario Central de Asturias ( Site 1900)

🇪🇸

Oviedo, Asturias, Spain

Hospital Universitario 12 de Octubre ( Site 1902)

🇪🇸

Madrid, Spain

Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 2009)

🇹🇷

Istanbul, Turkey

Hospital Regional Universitario de Malaga ( Site 1905)

🇪🇸

Malaga, Spain

Medipol Universite Hastanesi ( Site 2005)

🇹🇷

Istanbul, Turkey

Hospital Universitario Virgen Macarena-Unidad de Investigación Oncológica ( Site 1907)

🇪🇸

Sevilla, Spain

Grigoriev Institute for medical Radiology NAMS of Ukraine ( Site 2110)

🇺🇦

Kharkiv, Kharkivska Oblast, Ukraine

Ankara Bilkent Sehir Hastanesi ( Site 2007)

🇹🇷

Ankara, Turkey

Ege Universitesi Tip Fakultesi Hastanesi ( Site 2001)

🇹🇷

Izmir, Turkey

Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 2003)

🇹🇷

Istanbul, Turkey

LISOD. Hospital ( Site 2111)

🇺🇦

Pliuty, Kyiv, Ukraine

Medical Center of Yuriy Spizhenko LLC.-Clinical Trial ( Site 2104)

🇺🇦

Kapitanivka Village, Kyivska Oblast, Ukraine

Royal Infirmary Aberdeen ( Site 2403)

🇬🇧

Aberdeen, Aberdeen City, United Kingdom

Clinic of National Cancer Institute ( Site 2101)

🇺🇦

Kyiv, Kyivska Oblast, Ukraine

Kyiv City Clinical Oncology Center ( Site 2100)

🇺🇦

Kyiv, Ukraine

Ninewells Hospital and Medical School ( Site 2401)

🇬🇧

Dundee, Dundee City, United Kingdom

Guy s & St Thomas NHS Foundation Trust ( Site 2408)

🇬🇧

London, London, City Of, United Kingdom

Multicare Institute For Research And Innovation ( Site 0108)

🇺🇸

Tacoma, Washington, United States

Moffitt Cancer Center ( Site 0137)

🇺🇸

Tampa, Florida, United States

VA Ann Arbor Healthcare System ( Site 0050)

🇺🇸

Ann Arbor, Michigan, United States

Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0061)

🇺🇸

Omaha, Nebraska, United States

John Theurer Cancer Center ( Site 0064)

🇺🇸

Hackensack, New Jersey, United States

Memorial Sloan Kettering Cancer Center ( Site 0069)

🇺🇸

New York, New York, United States

Campbelltown Hospital ( Site 3002)

🇦🇺

Campbelltown, New South Wales, Australia

Cancer Hospital Chinese Academy Of Medical Sciences. Shenzhen Center ( Site 3113)

🇨🇳

Shenzhen, Guangdong, China

Second Xiangya Hospital of Central-South University ( Site 3128)

🇨🇳

Changsha, Hunan, China

CHU de Bordeaux Hop St ANDRE ( Site 1115)

🇫🇷

Bordeaux, Aquitaine, France

Zhejiang Cancer Hospital.... ( Site 3108)

🇨🇳

Hangzhou, Zhejiang, China

C.H. de Saint Quentin ( Site 1111)

🇫🇷

Saint Quentin, Aisne, France

University General Hospital of Herakleion ( Site 1202)

🇬🇷

Heraklion, Irakleio, Greece

CHU Grenoble -Hop Michallon ( Site 1102)

🇫🇷

Grenoble, Isere, France

Sotiria Regional Chest Diseases Hospital of Athens ( Site 1200)

🇬🇷

Athens, Attiki, Greece

Reformatus Pulmonologiai Centrum ( Site 1304)

🇭🇺

Torokbalint, Pest, Hungary

Takarazuka City Hospital ( Site 4013)

🇯🇵

Takarazuka, Hyogo, Japan

National Cancer Center Hospital ( Site 4015)

🇯🇵

Tokyo, Japan

Inje University Haeundae Paik Hospital ( Site 3307)

🇰🇷

Busan, Pusan-Kwangyokshi, Korea, Republic of

Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E. ( Site 1701)

🇵🇹

Porto, Portugal

Main Military Clinical Hospital n.a. N.N.Burdenko ( Site 1812)

🇷🇺

Moscow, Moskva, Russian Federation

Barts Health NHS Trust ( Site 2409)

🇬🇧

London, London, City Of, United Kingdom

Memorial Sloan Kettering- Commack ( Site 0132)

🇺🇸

Commack, New York, United States

Loma Linda University Cancer Center ( Site 0011)

🇺🇸

Loma Linda, California, United States

Memorial Sloan Kettering - Nassau ( Site 0131)

🇺🇸

Uniondale, New York, United States

Memorial Sloan Kettering - Monmouth ( Site 0135)

🇺🇸

Middletown, New Jersey, United States

Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 1105)

🇫🇷

Paris, Ile-de-France, France

Asan Medical Center ( Site 3308)

🇰🇷

Songpagu, Seoul, Korea, Republic of

The Christie NHS Foundation Trust ( Site 2405)

🇬🇧

Manchester, United Kingdom

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