Comparison of Efficacy and Safety of Tislelizumab (BGB-A317) Versus Docetaxel as Treatment in the Second- or Third-line Setting in Participants With Non-Small Cell Lung Cancer (NSCLC)
- Registration Number
- NCT03358875
- Lead Sponsor
- BeiGene
- Brief Summary
The purpose of this study is to show that tislelizumab will improve overall survival in participants with Stage IIIB or IV non-small cell lung cancer when compared to docetaxel in second or third-line treatment setting.
- Detailed Description
This is a randomized, open-label, multicenter Phase 3 study in adult participants with histologically confirmed, locally advanced or metastatic (Stage IIIB or IV), NSCLC (squamous or non-squamous) who have disease progression during or after a platinum-containing regimen.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 805
- Age ≥ 18 years.
- Signed Informed Consent Form.
- Histologically confirmed locally advanced or metastatic (Stage IIIB or IV) NSCLC of either squamous or non-squamous histology types with disease progression during or following treatment with at least one platinum-containing regimen, but no more than 2 lines of systemic therapy.
- Participants must be able to provide fresh or archival tumor tissues for central assessment of PD-L1 expression in tumor cells. Participants with non-squamous histology must provide evidence of not harboring sensitizing epidermal growth factor (EGFR) mutation tested by a histology-based method.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
- Adequate hematologic and end-organ function.
- Expected life span > 12 weeks.
- Willing to be compliance with birth control requirement during pre-specified study participating period
Key
- Prior therapies of docetaxel or treatment targeting programmed cell death protein 1 (PD-1), PD-L1 or cytotoxic T-lymphocyte associated protein 4 (CTLA-4).
- Harboring EGFR sensitizing mutation or anaplastic lymphoma kinase (ALK) gene translocation.
- Unresolved side effects of Grade 2 and above from prior anti-cancer therapies, except for adverse events (AEs) not constituting a likely safety risk (e.g. alopecia, rash, pigmentation, specific lab abnormalities).
- History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs).
- History of interstitial lung disease, non-infectious pneumonitis or participants with significantly impaired pulmonary function, or who require supplemental oxygen at baseline.
- With uncontrollable pleural effusion, pericardial effusion, or clinically significant ascites requiring interventional treatment.
- Active leptomeningeal disease or uncontrolled, untreated brain metastasis.
- Severe chronic or active infection requiring systemic treatment.
- Known human immunodeficiency virus (HIV) infection, participants with untreated chronic hepatitis B, active vaccination treatment.
- Insufficient cardiac functions and other underlying unfavorable cardiovascular conditions.
- Prior allogeneic stem cell transplantation or organ transplantation.
- Active autoimmune diseases or history of autoimmune diseases that may relapse.
- With conditions requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive medications.
- With severe underlying medical conditions (including laboratory abnormalities) or alcohol or drug abuse that may affect the explanation of drug toxicity or AEs or result in impaired compliance with study conduct.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Docetaxel Docetaxel Participants received docetaxel 75 mg/m² IV once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent, whichever occurred first. Tislelizumab Tislelizumab Participants received tislelizumab 200 mg intravenously (IV) once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent, whichever occurred first.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) in All Participants (Co-primary Endpoint) From randomization to the data cutoff date of 10 August 2020; up to 32.4 months OS was defined as the time from randomization to death from any cause. Median OS was calculated using the Kaplan-Meier method. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Data for participants who did not have postbaseline information were censored at the date of randomization.
Overall Survival (OS) in Programmed Cell Death Protein Ligand-1 (PD-L1)-Positive Participants (Co-primary Endpoint) From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months OS was defined as the time from randomization to death from any cause. Median OS was calculated using the Kaplan-Meier method. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Data for participants who did not have postbaseline information were censored at the date of randomization.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) in All Participants From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months Objective response rate is defined as the percentage of participants who had a complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Tumor assessments included computed tomography (CT) scans or magnetic resonance imaging (MRI), with preference for CT, of the chest, abdomen, and pelvis.
CR: Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.
PR: At least a 30% decrease in the size of target lesions and no progression of non-target lesions and no new lesions, or disappearance of all target lesions with persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits and no new lesions.Objective Response Rate in PD-L1-Positive Participants From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months Objective response rate is defined as the percentage of participants who had a complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Tumor assessments included computed tomography (CT) scans or magnetic resonance imaging (MRI), with preference for CT, of the chest, abdomen, and pelvis.
CR: Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.
PR: At least a 30% decrease in the size of target lesions and no progression of non-target lesions and no new lesions, or disappearance of all target lesions with persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits and no new lesions.Progression-free Survival (PFS) in All Participants From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months PFS was defined as the time from randomization to the first objectively documented disease progression as assessed by the investigator per RECIST v1.1 or death from any cause, whichever occurred first.
Median PFS was estimated using the Kaplan-Meier method.Progression-free Survival in PD-L1 Positive Participants From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months PFS was defined as the time from randomization to the first objectively documented disease progression as assessed by the investigator per RECIST v1.1 or death from any cause, whichever occurred first.
Median PFS was estimated using the Kaplan-Meier method.Duration of Response (DOR) for All Responders From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months DoR was defined as the time from the first documented objective response to documented disease progression as assessed by the investigator using RECIST v1.1, or death from any cause, whichever occurred first.
Median DOR was estimated using the Kaplan-Meier method.
Progressive Disease (PD): At least a 20% increase in the size of target lesions with an absolute increase of at least 5 mm, or unequivocal progression of existing non-target lesions, or the appearance of any new lesions.Duration of Response (DOR) in PD-L1-Positive Responders From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months DoR was defined as the time from the first documented objective response to documented disease progression as assessed by the investigator using RECIST v1.1, or death from any cause, whichever occurred first.
Median DOR was estimated using the Kaplan-Meier method.
Progressive Disease (PD): At least a 20% increase in the size of target lesions with an absolute increase of at least 5 mm, or unequivocal progression of existing non-target lesions, or the appearance of any new lesions.Change From Baseline in EORTC Quality of Life Questionnaire Lung Cancer 13 Items (QLQ-LC13) Coughing, Dyspnoea, and Chest Pain Scores Baseline and Cycle 6 (each cycle was 3 weeks) The EORTC QLQ-LC13 is the lung cancer module of the QLQ-C30 and measures lung cancer-specific disease and treatment symptoms. It includes 13 questions about specific symptoms in which participants respond based on a 4-point scale, where 1 is "not at all" and 4 is "very much". Raw scores are transformed into a 0 to 100 scale via linear transformation. Lower scores indicate an improvement in symptoms.
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/Quality of Life (QOL) Score Baseline and Cycle 6 (each cycle was 3 weeks) The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 = Not at all (best) and 4 = Very Much (worst) and two global health quality of life (QOL) questions answered on a 7-point scale where 1 = Very poor and 7 = Excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. Higher scores in GHS/QoL score indicates better quality of life.
Change From Baseline in European Quality of Life 5-Dimensions, 5-level (EQ-5D-5L) Visual Analogue Scale (VAS) Baseline and Cycle 6 (each cycle was 3 weeks) The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' A higher score indicates better health outcomes.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) From first dose of study drug to 30 days after last dose, up to the study completion date cut-off date of 18 January 2024 (up to approximately 63 months) An adverse event is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
The investigator assessed the severity of each AE and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03 as defined below:
* Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.
* Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate activities of daily living.
* Grade 3: Severe or medically significant but not immediately life threatening. hospitalization or prolongation of hospitalization indicated; disabling; limiting selfcare activities of daily living.
* Grade 4: Life threatening consequences; urgent intervention indicated.
* Grade 5: Death related to AE.
Trial Locations
- Locations (121)
Centrum Onkologii Instytut Im M Sklodowskiej Curie
🇵🇱Warszawa, Poland
Iu C, Clinical Research Excellence Application and Research Center
🇹🇷Stanbul, Turkey
Hospital Sao Lucas Da Pucrs
🇧🇷Porto Alegre, Brazil
Mhat For Womens Health Nadezhda, Ood
🇧🇬Sofia, Bulgaria
Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy
🇵🇱Otwock, Poland
Hgb Hospital Giovanni Battista Mae de Deus Center
🇧🇷Porto Alegre, Brazil
Hospital Haroldo Juacaba Instituto Do Cancer Do Ceara
🇧🇷Fortaleza, Brazil
Tianjin Union Medical Center (Nankai University Affiliated Hospital)
🇨🇳Tianjin, Tianjin, China
Mazowiecki Szpital Specjalistyczny W Ostrolece Im Dr Jozefa Psarskiego
🇵🇱Ostroleka, Poland
Hospital de Clinicas de Porto Alegre
🇧🇷Porto AlegreRS, Brazil
Nob Nucleo de Oncologia Da Bahia
🇧🇷Salvador, Brazil
Cepho Centro de Estudos E Pesquisas de Hematologia E Oncologia
🇧🇷Santo Andre, Brazil
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Chinese Pla General Hospital
🇨🇳Beijing, Beijing, China
The Affiliated Hospital of Zunyi Medical College
🇨🇳Zunyi, Guizhou, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Nantong Tumor Hospital Branch North
🇨🇳Nantong, Jiangsu, China
Xuzhou Central Hospital
🇨🇳Xuzhou, Jiangsu, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
The First Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
The First Affiliated Hospital of Xinjiang Medical University
🇨🇳Urumqi, Xinjiang, China
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, Zhejiang, China
Health Pharma Professional Research Sa de Cv
🇲🇽Ciudad de Mexico, Mexico
Fundacion Rodolfo Padilla Padilla, Ac
🇲🇽Leon, Mexico
Medica Sur
🇲🇽Mexico, Mexico
Hospital Bruno Born
🇧🇷Lajeado, Brazil
Umhat Deva Maria, Eood
🇧🇬Burgas, Bulgaria
Mhat Dobrich, Ad
🇧🇬Dobrich, Bulgaria
Izerskie Centrum Pulmonologii I Chemioterapii Izer Med Spolka Z Oo
🇵🇱Szklarska Porba, Poland
Fakultna Nemocnica S Poliklinikou Nove Zamky
🇸🇰Nove Zamky, Slovakia
Hospital de Amor Barretos
🇧🇷Barretos, Brazil
Hospital Evangelico de Cachoeiro de Itapemirim
🇧🇷Cachoeiro de Itapemirim, Brazil
Fundacao Doutor Amaral Carvalho
🇧🇷Jau, Brazil
Inca Instituto Nacional de Cancer
🇧🇷Rio de Janeiro, Brazil
The First Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
Guangzhou Institute of Respiratory Disease
🇨🇳Guangzhou, Guangdong, China
Hainan General Hospital
🇨🇳Haikou, Hainan, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
Changsha Central Hospital
🇨🇳Changsha, Hunan, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
Liaoning Cancer Hospital and Institute
🇨🇳Shenyang, Liaoning, China
Jinan Central Hospital
🇨🇳Jinan, Shandong, China
Hospital Sao Vicente de Paulo
🇧🇷Passo Fundo, Brazil
Szpital Specjalistyczny Brzeziny
🇵🇱Brzeziny, Poland
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
State Budgetary Healthcare Institution Volgograd Regional Clinical Oncology Dispensary
🇷🇺Volgograd, Volgogradskaya Oblast', Russian Federation
Fsbi National Medical Research Center For Oncology Na Nn Petrov of the Moh of the Rf
🇷🇺SaintPetersburg, Russian Federation
Vychodoslovensky Onkologicky Ustav, As
🇸🇰Kosice, Slovakia
Nemocnica S Poliklinikou Stefana Kukuru Michalovce, As
🇸🇰Michalovce, Slovakia
Tr Trakya University Health Research and Application Center (Hospital)
🇹🇷Edirne, Turkey
Oncosite Centro de Pesquisa Clinica Em Oncologia
🇧🇷Ijui, Brazil
Icesp Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de Oliveira
🇧🇷Sao Paulo, Brazil
Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
The First Affiliated Hospital of Xian Jiaotong University
🇨🇳Xian, Shaanxi, China
Shanghai Pulmonary Hospital
🇨🇳Shanghai, Shanghai, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, Tianjin, China
The First Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
Hospital of Lithuanian University of Health Sciences Kaunas Clinics Branch Oncology Hospital
🇱🇹Kaunas, Lithuania
National Cancer Institute
🇱🇹Vilnius, Lithuania
Investigacion Onco Farmaceutica (Oncotech)
🇲🇽La Paz, Mexico
Oaxaca Site Management Organization Sc
🇲🇽Oaxaca, Mexico
Vitamed Llc
🇷🇺Moscow, Moskva, Russian Federation
Hospital Nossa Senhora Da Conceicao
🇧🇷Porto Alegre, Brazil
Complex Oncology Center Rousse Eood
🇧🇬Rousse, Bulgaria
Centro de Investigacion Clinica Chapultepec Sa de Cv
🇲🇽Morelia, Mexico
Fsbi Russian Scientific Center of Radiology and Nuclear Medicine of the Moh of the Rf
🇷🇺Moscow, Moskva, Russian Federation
Fsbi Clinical Research and Practical Center For Specialized Medical Care (Oncology)
🇷🇺SanktPetersburg, Sankt-Peterburg, Russian Federation
Nemocnica S Poliklinikou Sv Jakuba, No Bardejov
🇸🇰Bardejov, Slovakia
Mhat Dr Tota Venkova, Ad
🇧🇬Gabrovo, Bulgaria
Cancer Hospital Chinese Academy of Medical Sciences
🇨🇳Beijing, Beijing, China
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
Daping Hospital, Third Military Medical University
🇨🇳Chongqing, Chongqing, China
Cancer Center of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
Cancer Hospital of Shantou University Medical College
🇨🇳Shantou, Guangdong, China
The Second Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Zhejiang University College of Medicine Second Affiliated Hospital
🇨🇳Hangzhou, Zhejiang, China
Hospital of Lithuanian University of Health Sciences Kaunas Clinics
🇱🇹Kaunas, Lithuania
Waikato Hospital
🇳🇿Hamilton Waikato, New Zealand
Salve Medica Sp Z Oo, Sp Komandytowa
🇵🇱Lodz, Poland
Zespol Gruzlicy I Chorob Pluc W Olsztynie Oddz Onkologii Z Pododdz Chemioterapii Nowotworow Puc
🇵🇱Olsztyn, Poland
Irkutsk Regional Oncology Dispensary
🇷🇺Irkutsk, Irkutiskaya Oblast', Russian Federation
Nonu Universitesi Tip Fakultesi
🇹🇷Battalgazi, Turkey
Sbei Hpe Ryazan State Medical University Na Academician Ip Pavlov of the Moh of the Rf
🇷🇺Ryazan, Ryazanskaya Oblast', Russian Federation
Narodny Onkologicky Ustav
🇸🇰Bratislava, Slovakia
Ege University Medical Faculty
🇹🇷Izmir, Turkey
Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto
🇧🇷Sao Jose do Rio Preto, Brazil
Acibadem City Clinic Mhat Tokuda Ead
🇧🇬Sofia, Bulgaria
Anhui Provincial Hospital
🇨🇳Hefei, Anhui, China
Beijing Chest Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
The First Affiliated Hospital of Guangxi Medical University
🇨🇳Nanning, Guangxi, China
Hubei Cancer Hospital
🇨🇳Wuhan, Hubei, China
Jiangsu Province Hospital
🇨🇳Nanjing, Jiangsu, China
Jiangxi Province Cancer Hospital
🇨🇳Nanchang, Jiangxi, China
Jilin Cancer Hospital
🇨🇳Changchun, Jilin, China
Centrum Terapii Wspolczesnej Jm Jasnorzewska Sp Komandytowo Akcyjna
🇵🇱Lodz, Poland
N N Blokhin Russian Cancer Research Center Konstantin Laktionov
🇷🇺Moscow, Moskva, Russian Federation
Poko Poprad Sro
🇸🇰Poprad, Slovakia
Bakirkoy Dr Sadi Konuk Teaching and Research Hospital
🇹🇷Istanbul, Turkey
Kocaeli Universitesi Tip Fakultesi
🇹🇷Kocaeli, Turkey
Namik Kemal University
🇹🇷Tekirdag, Turkey
Goztepe Prof Dr Suleyman Yalcin Ehir Hastanesi
🇹🇷Istanbul, Turkey
Linyi Cancer Hospital
🇨🇳Linyi, Shandong, China
Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
🇨🇳Chengdu, Sichuan, China
Yunnan Cancer Hospital
🇨🇳Kunming, Yunnan, China
Accelerium S de Rl de Cv
🇲🇽Monterrey, Mexico
Auckland City Hospital
🇳🇿Auckland, New Zealand
Tauranga Hospital
🇳🇿Tauranga, New Zealand
Pavlov First Saint Petersburg State Medical University
🇷🇺SaintPetersburg, Sankt-Peterburg, Russian Federation
Fakultna Nemocnica S Poliklinikou Fd Roosevelta
🇸🇰Banska Bystrica, Slovakia
Nemocnica Na Okraji Mesta, No
🇸🇰Partizanske, Slovakia
Arkhangelsk Regional Clinical Oncological Dispensary
🇷🇺Arkhangelsk, Arkhangel'skaya Oblast', Russian Federation
Fsbi of Higher Educationogarev Mordovia State University
🇷🇺Saransk, Mordoviya, Respublika, Russian Federation
Bih of Omsk Region Clinical Oncology Dispensary
🇷🇺Omsk, Omskaya Oblast', Russian Federation
Private Medical Institution Evromedservis
🇷🇺Pushkin, Sankt-Peterburg, Russian Federation
Llc Center of Palliative Medicine Devita
🇷🇺SaintPetersburg, Sankt-Peterburg, Russian Federation
Acibadem Adana Hospital
🇹🇷Adana, Turkey
Hacettepe University
🇹🇷Ankara, Turkey
Necmettin Erbakan University Selcuklu Faculty of Medicine
🇹🇷Meram, Turkey