Clinical trial NCT03745222: A Study of Tislelizumab (BGB-A317) Plus Chemoradiotherapy Followed by Tislelizumab Monotherapy in Newly Diagnosed, Stage III Subjects With Locally Advanced, Unresectable Non-small Cell Lung Cancer
Official title: A PHASE 3, RANDOMIZED, BLINDED, PLACEBO-CONTROLLED STUDY OF TISLELIZUMAB (BGB-A317) PLUS CHEMORADIOTHERAPY FOLLOWED BY TISLELIZUMAB MONOTHERAPY IN NEWLY DIAGNOSED, STAGE III SUBJECTS WITH LOCALLY ADVANCED, UNRESECTABLE NON-SMALL CELL LUNG CANCER
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Locally Advanced, Unresectable Non-Small Cell Lung Cancer
Non-Small Cell Lung Cancer
NSCLC
Randomized
BGB-A317
Tislelizumab
PD-1
Lead sponsor: Celgene
Sponsor class: INDUSTRY
Collaborators: name: BeiGene
First posted: 2018-11-19
Enrollment: 1
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 3, randomized, double-blind, placebo-controlled multicenter global study designed to compare the efficacy and safety of tislelizumab in combination with concurrent chemoradiotherapy (cCRT) followed by tislelizumab monotherapy versus cCRT alone, and tislelizumab given sequentially after cCRT versus cCRT alone, in newly diagnosed stage III subjects with locally advanced, unresectable non-small cell lung cancer (NSCLC). The primary endpoint is centrally-assessed progression free survival (PFS) in the intent-to-treat (ITT) population. .


Eligibility criteria: Inclusion Criteria:

1. Newly diagnosed, histologically confirmed, locally advanced, stage III unresectable non small cell lung cancer (NSCLC).

   Staging will be confirmed at screening by positron emission tomography-computed tomography (PET/CT) and brain imaging by magnetic resonance imaging (MRI) or computed tomography (CT) with contrast.
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
3. Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) gene translocation status available prior to randomization.
4. Provision of fresh or archival tumor tissue or discussion with Sponsor.
5. Adequate hematologic and end-organ function.

Exclusion Criteria:

1. Prior therapies including those targeting PD-1 or PD-L1 or chemotherapy, radiation, targeted therapy, biologic therapy, immunotherapy or investigational agent used to control non-small cell lung cancer (NSCLC).
2. History of severe hypersensitivity reactions to other monoclonal antibodies or any contraindication to the planned chemotherapy regimen.
3. History of, or ongoing, interstitial lung disease; pneumonitis requiring steroids; or clinically significant pericardial effusion.
4. Any active malignancy less than or equal to 2 years before randomization, with the exception of non-small cell lung cancer (NSCLC) and any locally recurring cancer that has been treated curatively.
5. Severe chronic or active infections including those requiring systemic antibacterial, antifungal or antiviral therapy; known human immunodeficiency virus (HIV) infection; untreated chronic hepatitis B or chronic hepatitis B virus carries or active hepatitis C; or active autoimmune disease.
6. Prior allogeneic stem cell transplantation or organ transplantation.
7. Significant cardiovascular disease or other condition which places the patient at risk.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Up to approximately 5 years; date of randomization to the date of tumor progression or death; until study withdrawal date of 26 June 2019
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 5 years; date of randomization to date of death from any cause.
measure: Overall Survival at 24 Months
timeFrame: Up to approximately 24 months
measure: Percentage of Participants Who Achieved a Best Overall Response of Complete Response or Partial Response
timeFrame: Up to approximately 5 years
measure: Duration of Response
timeFrame: Up to approximately 5 years
measure: Percentage of Participants Alive and Progression-Free at 12 Months (APF12)
timeFrame: Up to 12 months
measure: Percentage of Participants Alive and Progression-free at 18 Months (APF18)
timeFrame: Up to approximately 18 months
measure: Time to Distant Metastasis (TTDM)
timeFrame: Up to approximately 5 years
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug up to study withdrawal date of 26 June 2019; 15 days.
measure: Number of Participants With Lung Cancer Symptoms Assessed by the Corresponding Domains of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC-QLQ-C30) and Lung-Cancer Specific QLQ-LC13
timeFrame: Up to approximately 5 years
measure: Percentage of Participants Who Would Have Continued on to Monotherapy Phase
timeFrame: Up to approximately 5 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Jacksonville
country: United States
facility: Cancer Specialists of North Florida - Jacksonville
state: Florida
city: Winter Haven
country: United States
facility: Bond Clinic, P.A.
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Hazard
country: United States
facility: Appalachian Regional Healthcare, Inc.
state: Kentucky
city: Louisville
country: United States
facility: Norton Healthcare - Norton Cancer Institute
state: Kentucky
city: Bethesda
country: United States
facility: Center For Cancer and Blood Disorders
state: Maryland
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kettering
country: United States
facility: Dayton Physicians, LLC
state: Ohio
city: Youngstown
country: United States
facility: Mercy Health Youngstown Hospital, LLC
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Houston
country: United States
facility: Millennium Oncology
state: Texas
city: Spokane
country: United States
facility: Medical Oncology Associates, P.S.
state: Washington
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
city: Beijing
country: China
facility: Chinese PLA General Hospital / 307 Hospital
city: Beijing
country: China
facility: Beijing Cancer Hospital - Beijing Institute for Cancer Research
city: Bengbu Shi
country: China
facility: Bengbu Medical College - First Affiliated Hospital
city: Changchun Shi
country: China
facility: Jilin Province Cancer Hospital
city: Changchun
country: China
facility: First Hospital of Jilin University
city: Changsha-shi
country: China
facility: Central South University - Xiangya School of Medicine - Hunan Cancer Hospital
city: Changsha
country: China
facility: Central South University - Xiangya School of Medicine - Hunan Cancer Hospital
city: Chengdu
country: China
facility: Sichuan Cancer Hospital & Institute
city: Chengdu
country: China
facility: Sichuan University - West China Hospital
city: Foshan
country: China
facility: Foshan First People's Hospital
city: Fuzhou Shi
country: China
facility: Fujian Medical University - Fujian Provincial Cancer Hospital
city: Guangzhou
country: China
facility: Cancer Center of Guangzhou Medical University
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
city: Hangzhou
country: China
facility: Zhejiang University School of Medicine - The Second Affiliated Hospital
city: Hangzhou
country: China
facility: Zhejiang Medical University - Zhejiang Cancer Hospital
city: Harbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
city: Kunming Shi
country: China
facility: Yunnan Cancer Hospital
city: Nanning
country: China
facility: Guangxi Tumour Institute and Hospital
city: Nantong
country: China
facility: Nantong Tumor Hospital
city: Shanghai Shi
country: China
facility: Shanghai Chest Hospital
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shapingbaqu
country: China
facility: Chongqing Cancer Hospital
city: Shenyang Shi
country: China
facility: Liaoning Cancer Hospital & Institute
city: Urumqi
country: China
facility: The First Hospital of Xinjiang Medical University
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
city: Xi'an City
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
city: Xiamen
country: China
facility: First Hospital of Xiamen
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
city: Zhengzhou
country: China
facility: Zhengzhou University (ZZU) - Henan Cancer Hospital
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
city: Tampere
country: Finland
facility: Tampereen yliopistollinen sairaala
city: Turku
country: Finland
facility: Turku University Hospital
city: Caen Cedex 5
country: France
facility: Centre Francois Baclesse
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Saint Herblain
country: France
facility: Institut de Cancerologie de l'Ouest (ICO) - Saint-Herblain
city: Aurich
country: Germany
facility: Medical Study Company NORD-WEST GmbH Oncology Aurich
city: Berlin
country: Germany
facility: Helios Klinikum Emil Von Behring
city: Dusseldorf
country: Germany
facility: Florence Nightingale KH der Kaiserwerther Diakonie
city: Esslingen Am Neckar
country: Germany
facility: Klinikum Esslingen GmbH
city: Gauting
country: Germany
facility: Asklepios Fachkliniken Muenchen Gauting
city: Goslar
country: Germany
facility: Oncological practice Goslar
city: Hamm
country: Germany
facility: Evangelisches Krankenhaus Hamm
city: Kassel
country: Germany
facility: Health Nordhessen Holding AG - Klinikum Kassel - Medical Clinic IV
city: Koln
country: Germany
facility: Kliniken der Stadt Koln gGmbH - Krankenhaus Merheim
city: Loewenstein
country: Germany
facility: Klinik Loewenstein gGmbH
city: München
country: Germany
facility: LMU Klinikum der Universität
city: Schweiler
country: Germany
facility: St. Antonius-Hospital
city: Westerstede
country: Germany
facility: Medizinische Studiengesellschaft Nord-West
city: Athens
country: Greece
facility: Sotiria Chest Hospital of Athens
city: Athens
country: Greece
facility: IASO General
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion
city: Kifissia
country: Greece
facility: Agioi Anargyroi Cancer Hospital
city: Piraeus
country: Greece
facility: Metaxa Cancer Hospital of Piraeus
city: Pylaia
country: Greece
facility: Interbalkan Medical Center of Thessaloniki
city: Rio Patras
country: Greece
facility: University General Hospital of Patras
city: Thessaloniki
country: Greece
facility: Bioclinic Thessaloniki Galinos clinic
city: Thessaloniki
country: Greece
facility: EUROMEDICA General Clinic of Thessaloniki
city: Thessaloniki
country: Greece
facility: Papageorgiou General Hospital of Thessaloniki
city: Szekesfehervar
country: Hungary
facility: Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
city: Torokbalint
country: Hungary
facility: Pulmonary Institute Torokbalint
city: Dublin
country: Ireland
facility: Beacon Hospital
city: Dublin
country: Ireland
facility: St James Hospital
city: Limerick
country: Ireland
facility: MidWestern Regional Hospital
city: Catania
country: Italy
facility: Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele - Ospedale Gaspare Rodolico
city: Genova
country: Italy
facility: IRCCS AziendaOspedaliera Universitaria San Martino
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori (I.R.S.T.)
city: Roma
country: Italy
facility: Universita Campus Bio-Medico di Roma
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena di Roma
city: Habikino-shi
country: Japan
facility: Osaka Prefectural Medical Center for Respiratory and Allergic Diseases
city: Hirakata-shi
country: Japan
facility: Kansai Medical University Hospital
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Kanazawa-shi
country: Japan
facility: Kanazawa University Hospital
city: Matsusaka-shi
country: Japan
facility: Matsusaka Municipal Hospital
city: Minato-ku
country: Japan
facility: Toranomon Hospital
city: Morioka
country: Japan
facility: Iwate Medical University Hospital
city: Nagoya-shi
country: Japan
facility: National Hospital Organization - Nagoya Medical Center
city: Nagoya-shi
country: Japan
facility: Nagoya University Hospital
city: Niigata-shi
country: Japan
facility: Niigata Cancer Center Hospital
city: Osaka
country: Japan
facility: Osaka City University Hospital
city: Ota-ku
country: Japan
facility: Gunma Prefectural Cancer Center
city: Sagamihara
country: Japan
facility: Kitasato University Hospital
city: Sendai-shi
country: Japan
facility: Sendai Kousei Hospital
city: Yokohama-shi
country: Japan
facility: Kanagawa Cardiovascular and Respiratory Center
city: Yokohama-shi
country: Japan
facility: Yokohama Municipal Citizen's Hospital
city: Cheongju
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Suwon si
country: Korea, Republic of
facility: Ajou University Hospital
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum (VUMC)
city: Zutphen
country: Netherlands
facility: Gelre Hospitals
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Tauranga
country: New Zealand
facility: Tauranga Hospital
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. prof. Franciszka Lukaszczyka w Bydgoszczy
city: Gliwice
country: Poland
facility: Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie
city: Poznan
country: Poland
facility: Med Polonia Sp. z o.o. NSZOZ
city: Warszawa
country: Poland
facility: Centrum Onkologii-Instytut im.Marii Sklodowskiej-Curie
city: Amadora
country: Portugal
facility: Hospital Prof. Doutor Fernando Fonseca
city: Coimbra
country: Portugal
facility: Centro Hospitalar E Universitario de Coimbra EPE
city: Guimaraes
country: Portugal
facility: Centro Hospitalar do Alto Ave, Hospital da Senhora da Oliveira Guimaraes
city: Lisboa
country: Portugal
facility: CUF Descobertas Hospital
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto - Hospital de Santo António
city: Porto
country: Portugal
facility: CUF Porto Hospital
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe
city: Bucharest
country: Romania
facility: Oncology Institute Professor Doctor Alexandru Trestioreanu
city: Cluj-Napoca
country: Romania
facility: Prof. Dr. I. Chiricuta Institute of Oncology
city: Cluj-Napoca
country: Romania
facility: Medisprof SRL
city: Constanta
country: Romania
facility: Sf. Apostol Andrei Constanta Emergency Clinical County Hospital
city: Craiova
country: Romania
facility: Oncology Center Sfantul Nectarie
city: Timisoara
country: Romania
facility: Life Search SRL
city: Timisoara
country: Romania
facility: Oncocenter Clinical Oncology
city: Moscow
country: Russian Federation
facility: Principal Military Clinical Hospital n.a. N.N. Burdenko
city: Omsk
country: Russian Federation
facility: Omsk Regional Oncology Center
city: Ryazan
country: Russian Federation
facility: Ryazan State Medical University n.a. I.P. Pavlov
city: Saransk
country: Russian Federation
facility: Mordovia State University
city: St. Petersburg
country: Russian Federation
facility: Clinical Hospital of the Russian Academy of Sciences
city: St. Petersburg
country: Russian Federation
facility: GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology)
city: St. Petersburg
country: Russian Federation
facility: Research Oncology Institute of Rosmed Technologies n.a. prof. N.N. Petrov
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Raffles Hospital
city: A Coruna
country: Spain
facility: Hospital Universitario a Coruna
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
city: Las Palmas de Gran Canaria
country: Spain
facility: Insular-Maternal and Child University Hospital Complex
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Majadahonda, Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro-Majadahonda
city: Malaga
country: Spain
facility: Hospital General Carlos Haya
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Dalin
country: Taiwan
facility: Buddhist Dalin Tzu Chi General Hospital
city: Kaohsiung, San Ming Dist.
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: Kaohsiung
country: Taiwan
facility: E-DA Hospital
city: Niao-Sung Hsiang Kaohsiung County
country: Taiwan
facility: Chang Gung Medical Foundation, Kaohsiung Memorial Hospital
city: Taipei, Zhongzheng Dist.
country: Taiwan
facility: National Taiwan University Hospital
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital
city: Colchester
country: United Kingdom
facility: East Suffolk and North Essex NHS Foundation Trust - Colchester Hospital
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust - University College Hospital
city: London
country: United Kingdom
facility: Guys Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: Maidstone
country: United Kingdom
facility: Maidstone and Tunbridge Wells NHS Trust - Maidstone Hospital
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust - Wythenshawe Hospital - North West Lung Centre
city: Northwood
country: United Kingdom
facility: The Hillingdon Hospitals NHS Foundation Trust - Mount Vernon Hospital
city: Sheffield South Yorkshire
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust - Weston Park Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospitals Trust
Study officials:
affiliation: Celgene
name: Marie Nguyen, MD
role: STUDY_DIRECTOR
References: