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

Carcinoma, Non-Small-Cell Lung Clinical Trial

— RATIONALE001  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03745222
• Other study ID #: BGB-A317-NSCL-001
• Secondary ID: U1111-1216-42942
• Status: Terminated
• Phase: Phase 3
• Start date: May 22, 2019
• Est. completion date: June 26, 2019

Study information

• Verified date: June 2020
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. .

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: June 26, 2019
• Est. primary completion date: June 26, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Drug:
• Tislelizumab
PD-1 inhibitor (monoclonal antibody against PD-1)
• Concurrent chemoradiotherapy (cCRT)
Chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide per standard of care. Radiotherapy will also be given concurrently with chemotherapy.

Other:
• Placebo
Placebo

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Celgene	BeiGene

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  China,  Finland,  France,  Germany,  Greece,  Hungary,  Ireland,  Italy,  Japan,  Korea, Republic of,  Netherlands,  New Zealand,  Poland,  Portugal,  Romania,  Russian Federation,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	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.	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	Overall Survival (OS)	Overall survival was defined as the time between randomization of treatment and death from any cause.	Up to approximately 5 years; date of randomization to date of death from any cause.
Secondary	Overall Survival at 24 Months	Overall survival was defined as the time between randomization of treatment and death from any cause.	Up to approximately 24 months
Secondary	Percentage of Participants Who Achieved a Best Overall Response of Complete Response or Partial Response	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).	Up to approximately 5 years
Secondary	Duration of Response	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.	Up to approximately 5 years
Secondary	Percentage of Participants Alive and Progression-Free at 12 Months (APF12)	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	Up to 12 months
Secondary	Percentage of Participants Alive and Progression-free at 18 Months (APF18)	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	Up to approximately 18 months
Secondary	Time to Distant Metastasis (TTDM)	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.	Up to approximately 5 years
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs)	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."	From first dose of study drug up to study withdrawal date of 26 June 2019; 15 days.
Secondary	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	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.	Up to approximately 5 years
Secondary	Percentage of Participants Who Would Have Continued on to Monotherapy Phase	Included the percentage of participants who would have received at least one dose of tislelizumab or placebo in the monotherapy phase before progression.	Up to approximately 5 years