Clinical trial NCT05211895: A Global Study to Assess the Effects of Durvalumab + Domvanalimab Following Concurrent Chemoradiation in Participants With Stage III Unresectable NSCLC
Official title: A Phase III, Randomised, Double-blind, Placebo-controlled, Multicentre, International Study of Durvalumab Plus Domvanalimab(AB154) in Participants With Locally Advanced (Stage III), Unresectable Non-small Cell Lung Cancer Whose Disease Has Not Progressed Following Definitive Platinum-based Concurrent Chemoradiation Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Keywords: non-small cell lung cancer
locally advanced
NSCLC
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Arcus Biosciences, Inc.
First posted: 2022-01-27
Enrollment: 860
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase III, randomised, double-blind, placebo-controlled, multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736) and domvanalimab (AB154) compared with durvalumab plus placebo in adults with locally advanced (Stage III), unresectable NSCLC whose disease has not progressed following definitive platinum-based cCRT.


Eligibility criteria: INCLUSION CRITERIA:

1. Participant must be ≥ 18 years at the time of screening.
2. Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease
3. Provision of a tumour tissue sample obtained prior to CRT
4. Documented tumour PD-L1 status ≥ 1% by central lab
5. Documented EGFR and ALK wild-type status (local or central).
6. Patients must not have progressed following definitive, platinum-based, concurrent chemoradiotherapy
7. Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy
8. Participants must have received a total dose of radiation of 60 Gy ±10% (54 Gy to 66 Gy) as part of the chemoradiation therapy, to be randomised. Radiation therapy should be administered by intensity modulated RT (preferred) or 3D-conforming technique.
9. WHO performance status of 0 or 1 at randomization
10. Adequate organ and marrow function

EXCLUSION CRITERIA:

1. History of another primary malignancy, except for:

   * Malignancies treated with curative intent and adequate follow-up with no known active disease and have not required active treatment within the past 3 years before the first dose of study intervention and of low potential risk of recurrence.
   * Adequately resected non melanoma skin cancer or lentigo maligna without evidence of disease .
   * Adequately treated carcinoma in situ, including Ta tumors without evidence of disease.
2. Mixed small cell and non-small cell lung cancer histology.
3. Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC.
4. Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT.
5. Any unresolved toxicity CTCAE \>Grade 2 from the prior chemoradiation therapy (excluding alopecia).
6. Participants with ≥ grade 2 pneumonitis from prior chemoradiation therapy.
7. History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, or idiopathic pneumonitis - regardless of time of onset prior to randomisation. Evidence of active non-CRT induced pneumonitis (≥ Grade 2), active pneumonia, active ILD, active or recently treated pleural effusion, or current pulmonary fibrosis
8. Active or prior documented autoimmune or inflammatory disorders (with exceptions)
9. Active EBV infection, or known or suspected chronic active EBV infection at screening
10. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Up to 8 years after randomization
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Up to 8 years after randomization
measure: Overall Survival (OS)
timeFrame: Approximately 8 years after randomization
measure: Objective Response Rate (ORR)
timeFrame: Approximately 8 years after randomization
measure: Duration of Response (DoR)
timeFrame: Approximately 8 years after randomization
measure: Time from randomization to second progression (PFS2)
timeFrame: Approximately 8 years after randomization
measure: Time from randomization to first date of distant metastasis or death (TTDM)
timeFrame: Approximately 8 years after randomization
measure: Time to first subsequent therapy (TFST)
timeFrame: Approximately 8 years after randomization
measure: Concentration of Durvalumab and Domvanalimab
timeFrame: Approximately 12 weeks after last IP dose
measure: PFS6, PFS12, PFS18, PFS24
timeFrame: Approximately 6, 12, 18 and 24 months after randomization
measure: Anti-Drug Antibodies (ADAs)
timeFrame: Approximately 12 weeks after last IP dose.
measure: Time to deterioration in pulmonary symptoms (TTFCD)
timeFrame: Approximately 8 years after randomization
measure: PFS investigator
timeFrame: Up to 8 years after randomization
measure: OS 24
timeFrame: Approximately 24 months after randomization
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Research Site
state: Arizona
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Fountain Valley
country: United States
facility: Research Site
state: California
city: Santa Rosa
country: United States
facility: Research Site
state: California
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Jacksonville
country: United States
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state: Florida
city: Orlando
country: United States
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state: Florida
city: Saint Augustine
country: United States
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state: Florida
city: Macon
country: United States
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state: Georgia
city: Elmhurst
country: United States
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state: Illinois
city: Maywood
country: United States
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state: Illinois
city: Naperville
country: United States
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state: Illinois
city: Louisville
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state: Kentucky
city: Baltimore
country: United States
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state: Maryland
city: Silver Spring
country: United States
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state: Maryland
city: Detroit
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state: Michigan
city: Minneapolis
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city: Rochester
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state: Minnesota
city: East Brunswick
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state: New Jersey
city: Florham Park
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state: New Jersey
city: Buffalo
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state: New York
city: Johnson City
country: United States
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state: New York
city: Asheville
country: United States
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state: North Carolina
city: Asheville
country: United States
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state: North Carolina
city: Charlotte
country: United States
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state: North Carolina
city: Winston-Salem
country: United States
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state: North Carolina
city: Columbus
country: United States
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state: Ohio
city: Oklahoma City
country: United States
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state: Oklahoma
city: Pittsburgh
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state: Pennsylvania
city: Charleston
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state: South Carolina
city: Nashville
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state: Tennessee
city: Fort Sam Houston
country: United States
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state: Texas
city: Kingwood
country: United States
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state: Texas
city: Arlington
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state: Virginia
city: Fort Belvoir
country: United States
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state: Virginia
city: Spokane Valley
country: United States
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state: Washington
city: Appleton
country: United States
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state: Wisconsin
city: Brussels
country: Belgium
facility: Research Site
city: Edegem
country: Belgium
facility: Research Site
city: Haine-Saint-Paul
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Liege
country: Belgium
facility: Research Site
city: Sint-Niklaas
country: Belgium
facility: Research Site
city: Barretos
country: Brazil
facility: Research Site
city: Londrina
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Velho
country: Brazil
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city: Rio de Janeiro
country: Brazil
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city: Santo Andre
country: Brazil
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city: Sao Paulo
country: Brazil
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city: Sao Paulo
country: Brazil
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city: São Paulo
country: Brazil
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city: São Paulo
country: Brazil
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city: Taubaté
country: Brazil
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city: Calgary
country: Canada
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state: Alberta
city: Kelowna
country: Canada
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state: British Columbia
city: Laval
country: Canada
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state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Las Condes
country: Chile
facility: Research Site
city: Puerto Montt
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
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city: Santiago
country: Chile
facility: Research Site
city: Temuco
country: Chile
facility: Research Site
city: Aix en Provence
country: France
facility: Research Site
city: Angers
country: France
facility: Research Site
city: Bobigny
country: France
facility: Research Site
city: Clermont-Ferrand
country: France
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city: Lille
country: France
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city: Paris Cedex 14
country: France
facility: Research Site
city: Pau cedex
country: France
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city: Quimper
country: France
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city: Saint Gregoire
country: France
facility: Research Site
city: Saint-Quentin cedex
country: France
facility: Research Site
city: Vantoux
country: France
facility: Research Site
city: Villeurbanne
country: France
facility: Research Site
city: Berlin-Zehlendorf
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Braunschweig
country: Germany
facility: Research Site
city: Chemnitz
country: Germany
facility: Research Site
city: Erlangen
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Georgsmarienhuette
country: Germany
facility: Research Site
city: Giessen
country: Germany
facility: Research Site
city: Halle
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Homburg
country: Germany
facility: Research Site
city: Koblenz
country: Germany
facility: Research Site
city: Krefeld
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: Löwenstein
country: Germany
facility: Research Site
city: Moers
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Regensburg
country: Germany
facility: Research Site
city: Regensburg
country: Germany
facility: Research Site
city: Tübingen
country: Germany
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Holargos, Athens
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Hong Kong
country: Hong Kong
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city: Budapest
country: Hungary
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city: Budapest
country: Hungary
facility: Research Site
city: Deszk
country: Hungary
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city: Győr
country: Hungary
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city: Salgótarján
country: Hungary
facility: Research Site
city: Székesfehérvár
country: Hungary
facility: Research Site
city: Törökbálint
country: Hungary
facility: Research Site
city: Ahmedabad
country: India
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city: Bangalore
country: India
facility: Research Site
city: Bangalore
country: India
facility: Research Site
city: Delhi
country: India
facility: Research Site
city: Gurgaon
country: India
facility: Research Site
city: Howrah
country: India
facility: Research Site
city: Hyderabad
country: India
facility: Research Site
city: Jaipur
country: India
facility: Research Site
city: Kolkata
country: India
facility: Research Site
city: Marg Jaipur
country: India
facility: Research Site
city: Mohali
country: India
facility: Research Site
city: Namakkal
country: India
facility: Research Site
city: New Delhi
country: India
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city: New Delhi
country: India
facility: Research Site
city: Varanasi
country: India
facility: Research Site
city: Bergamo
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: Udine
country: Italy
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Bunkyo-ku
country: Japan
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city: Chiba-shi
country: Japan
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city: Fukuoka-shi
country: Japan
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city: Hidaka-shi
country: Japan
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city: Hirosaki-shi
country: Japan
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city: Itabashi-ku
country: Japan
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city: Kashihara-shi
country: Japan
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city: Koto-ku
country: Japan
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city: Kumamoto-shi
country: Japan
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city: Matsuyama-shi
country: Japan
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city: Nagoya-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
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city: Osakasayama-shi
country: Japan
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city: Sapporo-shi
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Tokyo
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
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city: Yokohama-shi
country: Japan
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Jinju-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon
country: Korea, Republic of
facility: Research Site
city: Johor Bahru
country: Malaysia
facility: Research Site
city: Kuala Lumpur
country: Malaysia
facility: Research Site
city: Kuching
country: Malaysia
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city: Selangor
country: Malaysia
facility: Research Site
city: Aguascalientes
country: Mexico
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city: Cdmx
country: Mexico
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city: Chihuahua
country: Mexico
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city: Guadalajara
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: Oaxaca
country: Mexico
facility: Research Site
city: San Pedro Garza Garcia
country: Mexico
facility: Research Site
city: Sonora
country: Mexico
facility: Research Site
city: Veracruz
country: Mexico
facility: Research Site
city: Bodø
country: Norway
facility: Research Site
city: Gjøvik
country: Norway
facility: Research Site
city: Oslo
country: Norway
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city: Trondheim
country: Norway
facility: Research Site
city: Bacolod
country: Philippines
facility: Research Site
city: Iloilo City
country: Philippines
facility: Research Site
city: Muntinlupa City
country: Philippines
facility: Research Site
city: Pasig City
country: Philippines
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city: Quezon City
country: Philippines
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city: Quezon City
country: Philippines
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Gliwice
country: Poland
facility: Research Site
city: Gliwice
country: Poland
facility: Research Site
city: Katowice
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Zielona Góra
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Bucuresti
country: Romania
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city: Bucuresti
country: Romania
facility: Research Site
city: Craiova
country: Romania
facility: Research Site
city: Floresti
country: Romania
facility: Research Site
city: Iasi
country: Romania
facility: Research Site
city: Oradea
country: Romania
facility: Research Site
city: Sibiu
country: Romania
facility: Research Site
city: Suceava
country: Romania
facility: Research Site
city: Timisoara
country: Romania
facility: Research Site
city: Amanzimtoti
country: South Africa
facility: Research Site
city: Amanzimtoti
country: South Africa
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Parktown
country: South Africa
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
city: Bilbao (Vizcaya)
country: Spain
facility: Research Site
city: Castello de la Plana
country: Spain
facility: Research Site
city: Cordoba
country: Spain
facility: Research Site
city: El Palmar
country: Spain
facility: Research Site
city: Palma de Mallorca
country: Spain
facility: Research Site
city: Sabadell (Barcelona)
country: Spain
facility: Research Site
city: Basel
country: Switzerland
facility: Research Site
city: Bern
country: Switzerland
facility: Research Site
city: Lausanne
country: Switzerland
facility: Research Site
city: Hsinchu
country: Taiwan
facility: Research Site
city: New-Taipei
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Adapazari
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Antalya
country: Turkey
facility: Research Site
city: Edirne
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Konya
country: Turkey
facility: Research Site
city: Çankaya
country: Turkey
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Brighton
country: United Kingdom
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Cardiff
country: United Kingdom
facility: Research Site
city: Cheltenham
country: United Kingdom
facility: Research Site
city: High Heaton/Newcastle Upon Tyn
country: United Kingdom
facility: Research Site
city: Leeds
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
Study officials:
affiliation: National Cancer Center Hospital
name: Hidehito Horinouchi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Virginia Cancer Specialists Research Institute
name: Alexander Spira, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Shandong Cancer Hospital and Institute
name: Jinming Yu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: