Clinical trial NCT03358875: 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)
Official title: A Phase 3, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of BGB-A317 (Anti-PD1 Antibody) Compared With Docetaxel in Patients With Non-Small Cell Lung Cancer Who Have Progressed on a Prior Platinum-Containing Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2017-12-02
Enrollment: 805
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: 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.

Eligibility criteria: Key Inclusion Criteria:

1. Age ≥ 18 years.
2. Signed Informed Consent Form.
3. 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.
4. 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.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
6. Adequate hematologic and end-organ function.
7. Expected life span \> 12 weeks.
8. Willing to be compliance with birth control requirement during pre-specified study participating period

Key Exclusion Criteria:

1. 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).
2. Harboring EGFR sensitizing mutation or anaplastic lymphoma kinase (ALK) gene translocation.
3. 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).
4. History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs).
5. History of interstitial lung disease, non-infectious pneumonitis or participants with significantly impaired pulmonary function, or who require supplemental oxygen at baseline.
6. With uncontrollable pleural effusion, pericardial effusion, or clinically significant ascites requiring interventional treatment.
7. Active leptomeningeal disease or uncontrolled, untreated brain metastasis.
8. Severe chronic or active infection requiring systemic treatment.
9. Known human immunodeficiency virus (HIV) infection, participants with untreated chronic hepatitis B, active vaccination treatment.
10. Insufficient cardiac functions and other underlying unfavorable cardiovascular conditions.
11. Prior allogeneic stem cell transplantation or organ transplantation.
12. Active autoimmune diseases or history of autoimmune diseases that may relapse.
13. With conditions requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone or equivalent) or other immunosuppressive medications.
14. 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.

Primary outcomes:
measure: Overall Survival (OS) in All Participants (Co-primary Endpoint)
timeFrame: From randomization to the data cutoff date of 10 August 2020; up to 32.4 months
measure: Overall Survival (OS) in Programmed Cell Death Protein Ligand-1 (PD-L1)-Positive Participants (Co-primary Endpoint)
timeFrame: From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months
Secondary outcomes:
measure: Objective Response Rate (ORR) in All Participants
timeFrame: From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months
measure: Objective Response Rate in PD-L1-Positive Participants
timeFrame: From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months
measure: Duration of Response (DOR) for All Responders
timeFrame: From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months
measure: Duration of Response (DOR) in PD-L1-Positive Responders
timeFrame: From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months
measure: Progression-free Survival (PFS) in All Participants
timeFrame: From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months
measure: Progression-free Survival in PD-L1 Positive Participants
timeFrame: From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months
measure: 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
timeFrame: Baseline and Cycle 6 (each cycle was 3 weeks)
measure: Change From Baseline in EORTC Quality of Life Questionnaire Lung Cancer 13 Items (QLQ-LC13) Coughing, Dyspnoea, and Chest Pain Scores
timeFrame: Baseline and Cycle 6 (each cycle was 3 weeks)
measure: Change From Baseline in European Quality of Life 5-Dimensions, 5-level (EQ-5D-5L) Visual Analogue Scale (VAS)
timeFrame: Baseline and Cycle 6 (each cycle was 3 weeks)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: 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)
Other outcomes:
Locations:
city: Barretos
country: Brazil
facility: Hospital de Amor Barretos
city: Cachoeiro de Itapemirim
country: Brazil
facility: Hospital Evangelico de Cachoeiro de Itapemirim
city: Fortaleza
country: Brazil
facility: Hospital Haroldo Juacaba Instituto Do Cancer Do Ceara
city: Ijui
country: Brazil
facility: Oncosite Centro de Pesquisa Clinica Em Oncologia
city: Jau
country: Brazil
facility: Fundacao Doutor Amaral Carvalho
city: Lajeado
country: Brazil
facility: Hospital Bruno Born
city: Passo Fundo
country: Brazil
facility: Hospital Sao Vicente de Paulo
city: Porto AlegreRS
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
city: Porto Alegre
country: Brazil
facility: Hgb Hospital Giovanni Battista Mae de Deus Center
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas Da Pucrs
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora Da Conceicao
city: Rio de Janeiro
country: Brazil
facility: Inca Instituto Nacional de Cancer
city: Salvador
country: Brazil
facility: Nob Nucleo de Oncologia Da Bahia
city: Santo Andre
country: Brazil
facility: Cepho Centro de Estudos E Pesquisas de Hematologia E Oncologia
city: Sao Jose do Rio Preto
country: Brazil
facility: Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto
city: Sao Paulo
country: Brazil
facility: Icesp Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de Oliveira
city: Burgas
country: Bulgaria
facility: Umhat Deva Maria, Eood
city: Dobrich
country: Bulgaria
facility: Mhat Dobrich, Ad
city: Gabrovo
country: Bulgaria
facility: Mhat Dr Tota Venkova, Ad
city: Rousse
country: Bulgaria
facility: Complex Oncology Center Rousse Eood
city: Sofia
country: Bulgaria
facility: Mhat For Womens Health Nadezhda, Ood
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic Mhat Tokuda Ead
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Beijing
country: China
facility: Chinese Pla General Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Chest Hospital, Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: Daping Hospital, Third Military Medical University
state: Chongqing
city: Guangzhou
country: China
facility: Cancer Center of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou Institute of Respiratory Disease
state: Guangdong
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Zunyi
country: China
facility: The Affiliated Hospital of Zunyi Medical College
state: Guizhou
city: Haikou
country: China
facility: Hainan General Hospital
state: Hainan
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Changsha
country: China
facility: Changsha Central Hospital
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nantong
country: China
facility: Nantong Tumor Hospital Branch North
state: Jiangsu
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Province Cancer Hospital
state: Jiangxi
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: Liaoning Cancer Hospital and Institute
state: Liaoning
city: Xian
country: China
facility: The First Affiliated Hospital of Xian Jiaotong University
state: Shaanxi
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi Cancer Hospital
state: Shandong
city: Shanghai
country: China
facility: Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
city: Chengdu
country: China
facility: Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Union Medical Center (Nankai University Affiliated Hospital)
state: Tianjin
city: Urumqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang University College of Medicine Second Affiliated Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kaunas Clinics Branch Oncology Hospital
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kaunas Clinics
city: Vilnius
country: Lithuania
facility: National Cancer Institute
city: Ciudad de Mexico
country: Mexico
facility: Health Pharma Professional Research Sa de Cv
city: La Paz
country: Mexico
facility: Investigacion Onco Farmaceutica (Oncotech)
city: Leon
country: Mexico
facility: Fundacion Rodolfo Padilla Padilla, Ac
city: Mexico
country: Mexico
facility: Medica Sur
city: Monterrey
country: Mexico
facility: Accelerium S de Rl de Cv
city: Morelia
country: Mexico
facility: Centro de Investigacion Clinica Chapultepec Sa de Cv
city: Oaxaca
country: Mexico
facility: Oaxaca Site Management Organization Sc
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Hamilton Waikato
country: New Zealand
facility: Waikato Hospital
city: Tauranga
country: New Zealand
facility: Tauranga Hospital
city: Brzeziny
country: Poland
facility: Szpital Specjalistyczny Brzeziny
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lodz
country: Poland
facility: Centrum Terapii Wspolczesnej Jm Jasnorzewska Sp Komandytowo Akcyjna
city: Lodz
country: Poland
facility: Salve Medica Sp Z Oo, Sp Komandytowa
city: Olsztyn
country: Poland
facility: Zespol Gruzlicy I Chorob Pluc W Olsztynie Oddz Onkologii Z Pododdz Chemioterapii Nowotworow Puc
city: Ostroleka
country: Poland
facility: Mazowiecki Szpital Specjalistyczny W Ostrolece Im Dr Jozefa Psarskiego
city: Otwock
country: Poland
facility: Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy
city: Szklarska Porba
country: Poland
facility: Izerskie Centrum Pulmonologii I Chemioterapii Izer Med Spolka Z Oo
city: Warszawa
country: Poland
facility: Centrum Onkologii Instytut Im M Sklodowskiej Curie
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Clinical Oncological Dispensary
state: Arkhangel'skaya Oblast'
city: Irkutsk
country: Russian Federation
facility: Irkutsk Regional Oncology Dispensary
state: Irkutiskaya Oblast'
city: Saransk
country: Russian Federation
facility: Fsbi of Higher Educationogarev Mordovia State University
state: Mordoviya, Respublika
city: Moscow
country: Russian Federation
facility: N N Blokhin Russian Cancer Research Center Konstantin Laktionov
state: Moskva
city: Moscow
country: Russian Federation
facility: Fsbi Russian Scientific Center of Radiology and Nuclear Medicine of the Moh of the Rf
state: Moskva
city: Moscow
country: Russian Federation
facility: Vitamed Llc
state: Moskva
city: Omsk
country: Russian Federation
facility: Bih of Omsk Region Clinical Oncology Dispensary
state: Omskaya Oblast'
city: Ryazan
country: Russian Federation
facility: Sbei Hpe Ryazan State Medical University Na Academician Ip Pavlov of the Moh of the Rf
state: Ryazanskaya Oblast'
city: Pushkin
country: Russian Federation
facility: Private Medical Institution Evromedservis
state: Sankt-Peterburg
city: SaintPetersburg
country: Russian Federation
facility: Pavlov First Saint Petersburg State Medical University
state: Sankt-Peterburg
city: SaintPetersburg
country: Russian Federation
facility: Llc Center of Palliative Medicine Devita
state: Sankt-Peterburg
city: SanktPetersburg
country: Russian Federation
facility: Fsbi Clinical Research and Practical Center For Specialized Medical Care (Oncology)
state: Sankt-Peterburg
city: Volgograd
country: Russian Federation
facility: State Budgetary Healthcare Institution Volgograd Regional Clinical Oncology Dispensary
state: Volgogradskaya Oblast'
city: SaintPetersburg
country: Russian Federation
facility: Fsbi National Medical Research Center For Oncology Na Nn Petrov of the Moh of the Rf
city: Banska Bystrica
country: Slovakia
facility: Fakultna Nemocnica S Poliklinikou Fd Roosevelta
city: Bardejov
country: Slovakia
facility: Nemocnica S Poliklinikou Sv Jakuba, No Bardejov
city: Bratislava
country: Slovakia
facility: Narodny Onkologicky Ustav
city: Kosice
country: Slovakia
facility: Vychodoslovensky Onkologicky Ustav, As
city: Michalovce
country: Slovakia
facility: Nemocnica S Poliklinikou Stefana Kukuru Michalovce, As
city: Nove Zamky
country: Slovakia
facility: Fakultna Nemocnica S Poliklinikou Nove Zamky
city: Partizanske
country: Slovakia
facility: Nemocnica Na Okraji Mesta, No
city: Poprad
country: Slovakia
facility: Poko Poprad Sro
city: Adana
country: Turkey
facility: Acibadem Adana Hospital
city: Ankara
country: Turkey
facility: Hacettepe University
city: Battalgazi
country: Turkey
facility: Nonu Universitesi Tip Fakultesi
city: Edirne
country: Turkey
facility: Tr Trakya University Health Research and Application Center (Hospital)
city: Istanbul
country: Turkey
facility: Bakirkoy Dr Sadi Konuk Teaching and Research Hospital
city: Istanbul
country: Turkey
facility: Goztepe Prof Dr Suleyman Yalcin Ehir Hastanesi
city: Izmir
country: Turkey
facility: Ege University Medical Faculty
city: Kocaeli
country: Turkey
facility: Kocaeli Universitesi Tip Fakultesi
city: Meram
country: Turkey
facility: Necmettin Erbakan University Selcuklu Faculty of Medicine
city: Stanbul
country: Turkey
facility: Iu C, Clinical Research Excellence Application and Research Center
city: Tekirdag
country: Turkey
facility: Namik Kemal University
Study officials:
affiliation: Shanghai Pulmonary Hospital, Shanghai, China
name: Caicun Zhou, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhou C, Huang D, Fan Y, Yu X, Liu Y, Shu Y, Ma Z, Wang Z, Cheng Y, Wang J, Hu S, Liu Z, Poddubskaya E, Disel U, Akopov A, Dvorkin M, Zheng W, Ma Y, Wang Y, Li S, Yu C, Rivalland G. Tislelizumab Versus Docetaxel in Patients With Previously Treated Advanced NSCLC (RATIONALE-303): A Phase 3, Open-Label, Randomized Controlled Trial. J Thorac Oncol. 2023 Jan;18(1):93-105. doi: 10.1016/j.jtho.2022.09.217. Epub 2022 Sep 29.
citation: Huang D, Zhou C, Barnes G, Ma Y, Li S, Zhan L, Tang B. The effects of tislelizumab treatment on the health-related quality of life of patients with advanced non-small cell lung cancer. Cancer Med. 2023 Aug;12(16):17403-17412. doi: 10.1002/cam4.6361. Epub 2023 Aug 17.