Clinical trial NCT03777657: Tislelizumab in Combination With Chemotherapy as First-Line Treatment in Adults With Inoperable, Locally Advanced or Metastatic Gastric, or Gastroesophageal Junction Carcinoma
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Clinical Study Comparing the Efficacy and Safety of Tislelizumab (BGB-A317) Plus Platinum and Fluoropyrimidine Versus Placebo Plus Platinum and Fluoropyrimidine as First-Line Treatment in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastric, or Gastroesophageal Junction Adenocarcinoma
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2018-12-17
Enrollment: 997
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 study was designed to compare the efficacy and safety of tislelizumab plus chemotherapy versus placebo plus chemotherapy as the first treatment (first-line) for adults diagnosed with locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.


Eligibility criteria: Key Inclusion Criteria:

1. Locally advanced unresectable or metastatic gastric cancer (GC) or gastroesophageal junction (GEJ) carcinoma and have histologically confirmed adenocarcinoma
2. No previous systemic therapy for locally advanced unresectable or metastatic gastric/GEJ cancer. NOTE: Participants may have received prior neoadjuvant or adjuvant therapy as long as it was completed and have no recurrence or disease progression for at least 6 months.
3. Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1 within 7 days prior to randomization
4. Adequate organ function ≤ 7 days prior to randomization

Key Exclusion Criteria:

1. Has squamous cell or undifferentiated or other histological type GC
2. Active leptomeningeal disease or uncontrolled brain metastasis
3. Diagnosed with gastric or GEJ adenocarcinoma with positive HER2
4. Prior therapy with an anti-programmed cell death protein-1 (PD-1), anti-programmed cell death protein ligand-1 (PD-L1), anti-programmed cell death protein ligand-2 (PD-L2), or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Overall Survival in PD-L1 Positive Participants
timeFrame: From randomization up to the primary analysis data cut-off date of 8 October 2021; Median (range) time on follow-up was 11.8 (0.1 - 33.4) months.
measure: Overall Survival in the Intent-to-Treat (ITT) Analysis Set
timeFrame: From randomization up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.
Secondary outcomes:
measure: Progression-free Survival (PFS) in PD-L1 Positive Participants
timeFrame: From randomization up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.
measure: Overall Response Rate (ORR) in PD-L1 Positive Participants
timeFrame: Response was assessed every 6 weeks for the first 48 weeks and every 9 weeks thereafter; up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.
measure: Progression-free Survival (PFS) in the ITT Analysis Set
timeFrame: From randomization up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.
measure: Overall Response Rate (ORR) in the ITT Analysis Set
timeFrame: Response was assessed every 6 weeks for the first 48 weeks and every 9 weeks thereafter; up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.
measure: Duration of Response (DOR) in PD-L1 Positive Participants
timeFrame: Response was assessed every 6 weeks for the first 48 weeks and every 9 weeks thereafter; up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.
measure: Duration of Response in the ITT Analysis Set
timeFrame: Response was assessed every 6 weeks for the first 48 weeks and every 9 weeks thereafter; up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) 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) and Physical Functioning Scores
timeFrame: Baseline and Cycles 4 and 6
measure: Change From Baseline in EORTC QLQ-C30 Fatigue Score
timeFrame: Baseline and Cycles 4 and 6
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Gastric Cancer Module QLQ-STO22 (EORTC QLQ-STO22)
timeFrame: Baseline and Cycles 4 and 6
measure: Change From Baseline in European Quality of Life 5-Dimensions, 5-level (EQ-5D-5L) Visual Analogue Scale (VAS)
timeFrame: Baseline and Cycles 4 and 6
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose of study drug to 30 days after last dose or the initiation of a new anticancer therapy, whichever occurred first, up to the end of study; maximum treatment duration was 59.3 months in Tislelizumab and 56.8 months in the Placebo group.
measure: Disease Control Rate in PD-L1 Positive Participants
timeFrame: Response was assessed every 6 weeks for the first 48 weeks and every 9 weeks thereafter; up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.
measure: Disease Control Rate in the ITT Analysis Set
timeFrame: Response was assessed every 6 weeks for the first 48 weeks and every 9 weeks thereafter; up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.
measure: Clinical Benefit Rate (CBR) in PD-L1 Positive Participants
timeFrame: Response was assessed every 6 weeks for the first 48 weeks and every 9 weeks thereafter; up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.
measure: Clinical Benefit Rate (CBR) in the ITT Analysis Set
timeFrame: Response was assessed every 6 weeks for the first 48 weeks and every 9 weeks thereafter; up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.
measure: Time to Response (TTR) in PD-L1 Positive Participants
timeFrame: From randomization up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.
measure: Time to Response (TTR) in the ITT Analysis Set
timeFrame: From randomization up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California Davis Health System
state: California
city: Newnan
country: United States
facility: Southeastern Regional Medical Center
state: Georgia
city: Columbus
country: United States
facility: Ohio State University Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology, Pllc Nashville
state: Tennessee
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Cancer Hospital Aka West Branch of Anhui Province Hospital
state: Anhui
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Chao Yang Hospital
state: Beijing
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
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 Luhe Hospital, Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: Daping Hospital, Third Military Medical University
state: Chongqing
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
state: Gansu
city: Foshan
country: China
facility: Foshan First Peoples Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat Sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial Peoples Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Peoples Hospital
state: Guangdong
city: Guilin
country: China
facility: Affiliated Hospital of Guilin Medical University
state: Guangxi
city: Haikou
country: China
facility: Hainan General Hospital
state: Hainan
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial Peoples Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union 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: Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School
state: Jiangsu
city: Nantong
country: China
facility: Nantong Tumor Hospital Branch South
state: Jiangsu
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
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: The General Hospital of Shenyang Military
state: Liaoning
city: Shenyang
country: China
facility: Liaoning Cancer Hospital and Institute
state: Liaoning
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi Cancer Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University Branch South
state: Shandong
city: Shanghai
country: China
facility: Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Affiliated Zhongshan Hospital of Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai General Hospital
state: Shanghai
city: Shanghai
country: China
facility: Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
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: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Doubs
country: France
facility: Chu Besancon Hopital Jean Minjoz
city: Marseille
country: France
facility: Hopital de La Timone
city: Meurthe Et Moselle
country: France
facility: Icl Alexis Vautrin
city: Montbeliard
country: France
facility: Hopital Nord Franche Comte Site Du Mittan
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Pessac
country: France
facility: Chu Bordeaux Hopital Haut Leveque
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Santorsola Malpighi
city: Milano
country: Italy
facility: Fondazione Irccs Istituto Nazionale Dei Tumori
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G Pascale
city: Padova
country: Italy
facility: Iov Istituto Oncologico Veneto Irccs
city: Pesaro
country: Italy
facility: Ao Ospedali Riuniti Marche Nord
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Roma
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Tor Vergata
city: San Giovanni Rotondo
country: Italy
facility: Irccs Ospedale Casa Sollievo Della Sofferenza
city: Siena
country: Italy
facility: Aou Senese Policlinico Santa Maria Alle Scotte
city: Torino
country: Italy
facility: Azienda Ospedaliera Citta Della Salute E Della Scienza Di Torino
city: Torrette
country: Italy
facility: Azienda Ospedaliera Universitaria Delle Marche
city: Chibashi
country: Japan
facility: Chiba Cancer Center
state: Chiba
city: Kamogawashi
country: Japan
facility: Tesshokai Kameda General Hospital
state: Chiba
city: Matsuyamashi
country: Japan
facility: Nho Shikoku Cancer Center
state: Ehime
city: Fukuokashi
country: Japan
facility: Nho Kyushu Cancer Center
state: Fukuoka
city: Otashi
country: Japan
facility: Gunma Prefectural Cancer Center
state: Gunma
city: Sapporoshi
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Amagasakishi
country: Japan
facility: Johas Kansai Rosai Hospital
state: Hyogo
city: Kanazawashi
country: Japan
facility: Ishikawa Prefectural Central Hospital
state: Ishikawa
city: Kitagun
country: Japan
facility: Kagawa University Hospital
state: Kagawa
city: Yokohamashi
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa
city: Yufushi
country: Japan
facility: Oita University Hospital
state: Oita
city: Kurashikishi
country: Japan
facility: Kurashiki Central Hospital
state: Okayama
city: Okayamashi
country: Japan
facility: Okayama University Hospital
state: Okayama
city: Izumishi
country: Japan
facility: Izumi City General Hospital
state: Osaka
city: Osakashi
country: Japan
facility: Nho Osaka National Hospital
state: Osaka
city: Suitashi
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Hidakashi
country: Japan
facility: Saitama Medical University International Medical Center
state: Saitama
city: Kitaadachigun
country: Japan
facility: Saitama Cancer Center
state: Saitama
city: Hamamatsushi
country: Japan
facility: Hamamatsu University School of Medicine, University Hospital
state: Shizuoka
city: Chuoku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Fuchushi
country: Japan
facility: Tokyo Metropolitan Tama Medical Center
state: Tokyo
city: Kotoku
country: Japan
facility: Cancer Institute Hospital of Jfcr
state: Tokyo
city: Shinjukuku
country: Japan
facility: Center Hospital of the National Center For Global Health and Medicine
state: Tokyo
city: Goyangsi
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seongnamsi
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Suwonsi
country: Korea, Republic of
facility: The Catholic University of Korea, St Vincents Hospital
state: Gyeonggi-do
city: Suwonsi
country: Korea, Republic of
facility: Ajou University Hospital
state: Gyeonggi-do
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
state: Gyeongsangbukdo
city: HwasunGun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Jeollanam-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Chung Ang University Hospital
state: Seoul Teugbyeolsi
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lodz
country: Poland
facility: Centrum Terapii Wspolczesnej Jm Jasnorzewska Sp Komandytowo Akcyjna
city: Poznan
country: Poland
facility: Przychodnia Med Polonia Sp Z Oo
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii Im Marii Skodowskiej Curie Pastwowy Instytut Badawczy
city: Rio Piedras
country: Puerto Rico
facility: Pan American Oncology Trials, Llc
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Clinical Oncological Dispensary
state: Arkhangel'skaya Oblast'
city: Ivanovo
country: Russian Federation
facility: Rbih Ivanovo Regional Oncological Dispensary
state: Ivanovskaya Oblast'
city: Moscow
country: Russian Federation
facility: Vitamed Llc
state: Moskva
city: Novosibirsk
country: Russian Federation
facility: Sbhi of Novosibirsk Region Novosibirsk Regional Oncological Dispensary
state: Novosibirskaya Oblast'
city: Omsk
country: Russian Federation
facility: Bih of Omsk Region Clinical Oncology Dispensary
state: Omskaya Oblast'
city: Samara
country: Russian Federation
facility: Private Educational Institution of Higher Education Medical University Reaviz
state: Samaraskaya Oblast'
city: SaintPetersburg
country: Russian Federation
facility: Pavlov First Saint Petersburg State Medical University
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: Yaroslavl
country: Russian Federation
facility: Sbih of Yaroslavl Region Regional Clinical Oncological Hospital
state: Yaroslavskaya Oblast'
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Bilbao
country: Spain
facility: Hospital de Basurto
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Hm Madrid Sanchinarro
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Initia Oncologia, Slp
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung Ho Memorial Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Adana
country: Turkey
facility: Acibadem Adana Hospital
city: Ankara
country: Turkey
facility: Dr Abdurrahman Yurtaslan Oncology Teaching and Research Hospital
city: Battalgazi
country: Turkey
facility: Nonu Universitesi Tip Fakultesi
city: Diyarbakir
country: Turkey
facility: Dicle University Medical Faculty
city: Konyaalt
country: Turkey
facility: Akdeniz University Hospital
city: Stanbul
country: Turkey
facility: Iu C, Clinical Research Excellence Application and Research Center
city: Tekirdag
country: Turkey
facility: Namik Kemal University
city: Trabzon
country: Turkey
facility: Karadeniz Tecnical Uni Med Fac
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute Uk
Study officials:
affiliation: BeiGene
name: Jin Wang, MD
role: STUDY_DIRECTOR
References: