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
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Interventions
- Registration Number
- NCT03745222
- Lead Sponsor
- Celgene
- 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. .
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 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.
-
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
-
Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) gene translocation status available prior to randomization.
-
Provision of fresh or archival tumor tissue or discussion with Sponsor.
-
Adequate hematologic and end-organ function.
- 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).
- History of severe hypersensitivity reactions to other monoclonal antibodies or any contraindication to the planned chemotherapy regimen.
- History of, or ongoing, interstitial lung disease; pneumonitis requiring steroids; or clinically significant pericardial effusion.
- 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.
- 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.
- Prior allogeneic stem cell transplantation or organ transplantation.
- Significant cardiovascular disease or other condition which places the patient at risk.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1:Tislelizumab + cCRT followed by tislelizumab monotherapy Concurrent chemoradiotherapy (cCRT) Tislelizumab 200 mg is administered by intravenous (IV) administration and given together upfront with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by tislelizumab 200 mg by IV adminstration monotherapy. The standard platinum-based chemotherapy options include carboplatin/ paclitaxel and cisplatin/etoposide Arm 2: Placebo + cCRT followed by tislelizumab monotherapy Concurrent chemoradiotherapy (cCRT) Placebo is given with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by tislelizumab 200 mg by IV administration monotherapy. The standard platinum-based chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide. Arm 3: Placebo + cCRT followed by placebo monotherapy Concurrent chemoradiotherapy (cCRT) Placebo is given with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by placebo monotherapy. The standard platinum-based chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide. Arm 2: Placebo + cCRT followed by tislelizumab monotherapy Placebo Placebo is given with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by tislelizumab 200 mg by IV administration monotherapy. The standard platinum-based chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide. Arm 3: Placebo + cCRT followed by placebo monotherapy Placebo Placebo is given with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by placebo monotherapy. The standard platinum-based chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide. Arm 1:Tislelizumab + cCRT followed by tislelizumab monotherapy Tislelizumab Tislelizumab 200 mg is administered by intravenous (IV) administration and given together upfront with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by tislelizumab 200 mg by IV adminstration monotherapy. The standard platinum-based chemotherapy options include carboplatin/ paclitaxel and cisplatin/etoposide Arm 2: Placebo + cCRT followed by tislelizumab monotherapy Tislelizumab Placebo is given with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by tislelizumab 200 mg by IV administration monotherapy. The standard platinum-based chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Up to approximately 5 years; date of randomization to the date of tumor progression or death; until study withdrawal date of 26 June 2019 Progression-free survival was defined as the time from the date of randomization to the date of the first objectively tumor progression as assessed by the blinded independent central review per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria (documented by radiological assessment) or death (any cause) on or prior to the clinical cut-off date, which ever occurred first. Stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for Progressive disease (PD)• Progressive Disease- At least a 20% increase in the sum of diameters of target lesions from nadir.
- Secondary Outcome Measures
Name Time Method Overall Survival at 24 Months Up to approximately 24 months Overall survival was defined as the time between randomization of treatment and death from any cause.
Duration of Response Up to approximately 5 years Duration of Response is defined as the time from the first occurrence of a documented objective response to the time of relapse, as determined by blinded independent central review per RECIST v1.1, or death from any cause, whichever comes first.
Overall Survival (OS) Up to approximately 5 years; date of randomization to date of death from any cause. Overall survival was defined as the time between randomization of treatment and death from any cause.
Percentage of Participants Who Achieved a Best Overall Response of Complete Response or Partial Response Up to approximately 5 years Overall Response was defined as percentage of participants who had a radiologic confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) guidelines, between Day 1 of treatment and subsequent anti-cancer therapy, death or study discontinuation. Complete response was defined as the disappearance of all target lesions; partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions from baseline; stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for progressive disease (PD).
Percentage of Participants Alive and Progression-Free at 12 Months (APF12) Up to 12 months Progression-free survival was defined as the time from the date of randomization to the date of the first objectively tumor progression as assessed by the blinded independent central review per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria (documented by radiological assessment) or death (any cause) on or prior to the clinical cut-off date, which ever occurred first
Percentage of Participants Who Would Have Continued on to Monotherapy Phase Up to approximately 5 years Included the percentage of participants who would have received at least one dose of tislelizumab or placebo in the monotherapy phase before progression.
Percentage of Participants Alive and Progression-free at 18 Months (APF18) Up to approximately 18 months Progression-free survival was defined as the time from the date of randomization to the date of the first objectively tumor progression as assessed by the blinded independent central review per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria (documented by radiological assessment) or death (any cause) on or prior to the clinical cut-off date, which ever occurred first
Time to Distant Metastasis (TTDM) Up to approximately 5 years TTDM was defined as the time from the date of randomization until the first date of distant metastasis or death in the absence of distant metastasis. Distant metastasis was defined as any new lesion that is outside of the radiation field according to RECIST v1.1 or proven by biopsy.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) From first dose of study drug up to study withdrawal date of 26 June 2019; 15 days. TEAEs include any adverse events (AEs) that had an onset date or a worsening in severity from baseline on or after the first dose of study drug up to 30 days following study drug discontinuation or initiation of new anticancer therapy, whichever occurred first. TEAEs also included all immune-related AEs recorded up to 90 days after the last dose of tislelizumab or placebo, regardless of whether or not the particpant started a new anticancer therapy. In addition, any serious AE with an onset date more than 30 days after the last dose of study drug that is assessed by the investigator as related to study drug were considered a TEAE."
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 Up to approximately 5 years The EORTC QLQ-C30 is a 30-item, questionnaire assessing quality of life (QoL), psychosocial burden and physical symptoms. It is classified into 15 domains: 5 functional subscales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning); 3 multi-item symptom subscales (fatigue, nausea/vomiting, and pain); each item is measured on a 4 point response scale; (not at all, a little, quite a bit, very much), with the exception of the 2 items measuring global health and QoL, (measured on a 7-point response scale). Scores are linearly transformed to 0 to 100 scores. Scores vary from 0 (worst) to 100 (best) for the functional dimensions and GHS, and from 0 (best) to 100 (worst) for the symptom dimensions; higher scores = better QoL, better functioning, or more severe symptoms, respectively. The LC13 covers 13 typical symptoms of lung cancer patients, such as coughing, pain, dyspnea, sore mouth, peripheral neuropathy, and hair loss.
Trial Locations
- Locations (163)
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Fort Wayne Medical Oncology and Hematology
🇺🇸Fort Wayne, Indiana, United States
Dayton Physicians, LLC
🇺🇸Kettering, Ohio, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Sichuan University - West China Hospital
🇨🇳Chengdu, China
Fujian Medical University - Fujian Provincial Cancer Hospital
🇨🇳Fuzhou Shi, China
Cancer Center of Guangzhou Medical University
🇨🇳Guangzhou, China
Yunnan Cancer Hospital
🇨🇳Kunming Shi, China
Guangxi Tumour Institute and Hospital
🇨🇳Nanning, China
Chongqing Cancer Hospital
🇨🇳Shapingbaqu, China
Liaoning Cancer Hospital & Institute
🇨🇳Shenyang Shi, China
The First Hospital of Xinjiang Medical University
🇨🇳Urumqi, China
Zhongnan Hospital of Wuhan University
🇨🇳Wuhan, China
Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
🇨🇳Wuhan, China
First Hospital of Xiamen
🇨🇳Xiamen, China
Zhengzhou University (ZZU) - Henan Cancer Hospital
🇨🇳Zhengzhou, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, China
Agioi Anargyroi Cancer Hospital
🇬🇷Kifissia, Greece
Sotiria Chest Hospital of Athens
🇬🇷Athens, Greece
Kansai Medical University Hospital
🇯🇵Hirakata-shi, Japan
Matsusaka Municipal Hospital
🇯🇵Matsusaka-shi, Japan
Yokohama Municipal Citizen's Hospital
🇯🇵Yokohama-shi, Japan
Med Polonia Sp. z o.o. NSZOZ
🇵🇱Poznan, Poland
Tampereen yliopistollinen sairaala
🇫🇮Tampere, Finland
Pulmonary Institute Torokbalint
🇭🇺Torokbalint, Hungary
Iwate Medical University Hospital
🇯🇵Morioka, Japan
Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie
🇵🇱Gliwice, Poland
Centro Hospitalar do Alto Ave, Hospital da Senhora da Oliveira Guimaraes
🇵🇹Guimaraes, Portugal
Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe
🇵🇹Porto, Portugal
Prof. Dr. I. Chiricuta Institute of Oncology
🇷🇴Cluj-Napoca, Romania
Ryazan State Medical University n.a. I.P. Pavlov
🇷🇺Ryazan, Russian Federation
Turku University Hospital
🇫🇮Turku, Finland
Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
🇭🇺Szekesfehervar, Hungary
Niigata Cancer Center Hospital
🇯🇵Niigata-shi, Japan
Sendai Kousei Hospital
🇯🇵Sendai-shi, Japan
Beacon Hospital
🇮🇪Dublin, Ireland
MidWestern Regional Hospital
🇮🇪Limerick, Ireland
Nagoya University Hospital
🇯🇵Nagoya-shi, Japan
Osaka City University Hospital
🇯🇵Osaka, Japan
Kitasato University Hospital
🇯🇵Sagamihara, Japan
Kanagawa Cardiovascular and Respiratory Center
🇯🇵Yokohama-shi, Japan
Vrije Universiteit Medisch Centrum (VUMC)
🇳🇱Amsterdam, Netherlands
CUF Porto Hospital
🇵🇹Porto, Portugal
Research Oncology Institute of Rosmed Technologies n.a. prof. N.N. Petrov
🇷🇺St. Petersburg, Russian Federation
Kaohsiung Medical University Hospital
🇨🇳Kaohsiung, San Ming Dist., Taiwan
National Hospital Organization - Nagoya Medical Center
🇯🇵Nagoya-shi, Japan
Gelre Hospitals
🇳🇱Zutphen, Netherlands
Medisprof SRL
🇷🇴Cluj-Napoca, Romania
Sf. Apostol Andrei Constanta Emergency Clinical County Hospital
🇷🇴Constanta, Romania
Oncology Center Sfantul Nectarie
🇷🇴Craiova, Romania
Buddhist Dalin Tzu Chi General Hospital
🇨🇳Dalin, Taiwan
Centrum Onkologii-Instytut im.Marii Sklodowskiej-Curie
🇵🇱Warszawa, Poland
Oncology Institute Professor Doctor Alexandru Trestioreanu
🇷🇴Bucharest, Romania
Mordovia State University
🇷🇺Saransk, Russian Federation
CUF Descobertas Hospital
🇵🇹Lisboa, Portugal
Centro Hospitalar do Porto - Hospital de Santo António
🇵🇹Porto, Portugal
Oncocenter Clinical Oncology
🇷🇴Timisoara, Romania
E-DA Hospital
🇨🇳Kaohsiung, Taiwan
Chang Gung Medical Foundation, Kaohsiung Memorial Hospital
🇨🇳Niao-Sung Hsiang Kaohsiung County, Taiwan
Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori (I.R.S.T.)
🇮🇹Meldola, Italy
Cancer Hospital Chinese Academy of Medical Sciences
🇨🇳Beijing, China
Bengbu Medical College - First Affiliated Hospital
🇨🇳Bengbu Shi, China
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
Appalachian Regional Healthcare, Inc.
🇺🇸Hazard, Kentucky, United States
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Center For Cancer and Blood Disorders
🇺🇸Bethesda, Maryland, United States
Universitair Ziekenhuis Brussel
🇧🇪Brussels, Belgium
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Beijing Cancer Hospital - Beijing Institute for Cancer Research
🇨🇳Beijing, China
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Mercy Health Youngstown Hospital, LLC
🇺🇸Youngstown, Ohio, United States
Medical Oncology Associates, P.S.
🇺🇸Spokane, Washington, United States
Chinese PLA General Hospital / 307 Hospital
🇨🇳Beijing, China
Jilin Province Cancer Hospital
🇨🇳Changchun Shi, China
Central South University - Xiangya School of Medicine - Hunan Cancer Hospital
🇨🇳Changsha, China
First Hospital of Jilin University
🇨🇳Changchun, China
Sichuan Cancer Hospital & Institute
🇨🇳Chengdu, China
Foshan First People's Hospital
🇨🇳Foshan, China
The First Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, China
Shanghai Chest Hospital
🇨🇳Shanghai Shi, China
Zhejiang University School of Medicine - The Second Affiliated Hospital
🇨🇳Hangzhou, China
Zhejiang Medical University - Zhejiang Cancer Hospital
🇨🇳Hangzhou, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, China
The Affiliated Hospital of Xuzhou Medical University
🇨🇳Xuzhou, China
Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele - Ospedale Gaspare Rodolico
🇮🇹Catania, Italy
Centre Francois Baclesse
🇫🇷Caen Cedex 5, France
Health Nordhessen Holding AG - Klinikum Kassel - Medical Clinic IV
🇩🇪Kassel, Germany
Helios Klinikum Emil Von Behring
🇩🇪Berlin, Germany
The First Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Xi'an City, China
Istituto Nazionale Tumori Regina Elena di Roma
🇮🇹Roma, Italy
The First Affiliated Hospital of Harbin Medical University
🇨🇳Harbin, China
Nantong Tumor Hospital
🇨🇳Nantong, China
Institut de Cancerologie de l'Ouest (ICO) - Saint-Herblain
🇫🇷Saint Herblain, France
Metaxa Cancer Hospital of Piraeus
🇬🇷Piraeus, Greece
Interbalkan Medical Center of Thessaloniki
🇬🇷Pylaia, Greece
Medical Study Company NORD-WEST GmbH Oncology Aurich
🇩🇪Aurich, Germany
St. Antonius-Hospital
🇩🇪Schweiler, Germany
Clinique Victor Hugo
🇫🇷Le Mans, France
Asklepios Fachkliniken Muenchen Gauting
🇩🇪Gauting, Germany
University General Hospital of Patras
🇬🇷Rio Patras, Greece
Florence Nightingale KH der Kaiserwerther Diakonie
🇩🇪Dusseldorf, Germany
Oncological practice Goslar
🇩🇪Goslar, Germany
Kliniken der Stadt Koln gGmbH - Krankenhaus Merheim
🇩🇪Koln, Germany
Evangelisches Krankenhaus Hamm
🇩🇪Hamm, Germany
IASO General
🇬🇷Athens, Greece
University General Hospital of Heraklion
🇬🇷Heraklion, Greece
Klinik Loewenstein gGmbH
🇩🇪Loewenstein, Germany
Medizinische Studiengesellschaft Nord-West
🇩🇪Westerstede, Germany
Papageorgiou General Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
St James Hospital
🇮🇪Dublin, Ireland
Kanazawa University Hospital
🇯🇵Kanazawa-shi, Japan
IRCCS AziendaOspedaliera Universitaria San Martino
🇮🇹Genova, Italy
Universita Campus Bio-Medico di Roma
🇮🇹Roma, Italy
Osaka Prefectural Medical Center for Respiratory and Allergic Diseases
🇯🇵Habikino-shi, Japan
Waikato Hospital
🇳🇿Hamilton, New Zealand
Hiroshima University Hospital
🇯🇵Hiroshima, Japan
Toranomon Hospital
🇯🇵Minato-ku, Japan
Gunma Prefectural Cancer Center
🇯🇵Ota-ku, Japan
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Universitario a Coruna
🇪🇸A Coruna, Spain
Centrum Onkologii im. prof. Franciszka Lukaszczyka w Bydgoszczy
🇵🇱Bydgoszcz, Poland
Hospital Prof. Doutor Fernando Fonseca
🇵🇹Amadora, Portugal
Centro Hospitalar E Universitario de Coimbra EPE
🇵🇹Coimbra, Portugal
Life Search SRL
🇷🇴Timisoara, Romania
Omsk Regional Oncology Center
🇷🇺Omsk, Russian Federation
GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology)
🇷🇺St. Petersburg, Russian Federation
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Spain
Hospital Universitario Germans Trias i Pujol
🇪🇸Barcelona, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital General Universitario de Alicante
🇪🇸Alicante, Spain
Hospital Universitario Puerta de Hierro-Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Raffles Hospital
🇸🇬Singapore, Singapore
Hospital General Carlos Haya
🇪🇸Malaga, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸Valencia, Spain
Manchester University NHS Foundation Trust - Wythenshawe Hospital - North West Lung Centre
🇬🇧Manchester, United Kingdom
Maidstone and Tunbridge Wells NHS Trust - Maidstone Hospital
🇬🇧Maidstone, United Kingdom
University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
East Suffolk and North Essex NHS Foundation Trust - Colchester Hospital
🇬🇧Colchester, United Kingdom
The Hillingdon Hospitals NHS Foundation Trust - Mount Vernon Hospital
🇬🇧Northwood, United Kingdom
University College London Hospitals NHS Foundation Trust - University College Hospital
🇬🇧London, United Kingdom
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
LMU Klinikum der Universität
🇩🇪München, Germany
Norton Healthcare - Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Cancer Specialists of North Florida - Jacksonville
🇺🇸Jacksonville, Florida, United States
Bond Clinic, P.A.
🇺🇸Winter Haven, Florida, United States
Millennium Oncology
🇺🇸Houston, Texas, United States
Klinikum Esslingen GmbH
🇩🇪Esslingen Am Neckar, Germany
EUROMEDICA General Clinic of Thessaloniki
🇬🇷Thessaloniki, Greece
Bioclinic Thessaloniki Galinos clinic
🇬🇷Thessaloniki, Greece
Ajou University Hospital
🇰🇷Suwon si, Korea, Republic of
Chungbuk National University Hospital
🇰🇷Cheongju, Korea, Republic of
Tauranga Hospital
🇳🇿Tauranga, New Zealand
Principal Military Clinical Hospital n.a. N.N. Burdenko
🇷🇺Moscow, Russian Federation
Clinical Hospital of the Russian Academy of Sciences
🇷🇺St. Petersburg, Russian Federation
National University Hospital
🇸🇬Singapore, Singapore
Guys Hospital
🇬🇧London, United Kingdom
National Taiwan University Hospital
🇨🇳Taipei, Zhongzheng Dist., Taiwan
Insular-Maternal and Child University Hospital Complex
🇪🇸Las Palmas de Gran Canaria, Spain
Royal Marsden Hospital
🇬🇧London, United Kingdom
Royal Cornwall Hospitals Trust
🇬🇧Truro, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust - Weston Park Hospital
🇬🇧Sheffield South Yorkshire, United Kingdom