A Study Evaluating the Efficacy and Safety of Tislelizumab Versus Chemotherapy in Advanced Non-Squamous Non-small Cell Lung Cancer

A Phase 3, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Tislelizumab (BGB-A317) (Anti-PD1 Antibody) Combined With Platinum-Pemetrexed Versus Platinum-Pemetrexed Alone as First-line Treatment for Patients With Stage IIIB or IV Non-Squamous Non-Small Cell Lung Cancer

This study evaluated the efficacy and safety of tislelizumab in combination with platinum (cisplatin or carboplatin) and pemetrexed compared with platinum and pemetrexed alone as first-line treatment in participants with Stage IIIB or IV non-squamous non-small cell lung cancer (NSCLC).

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Tislelizumab

• Study Type: Interventional
• Enrollment (Actual): 334
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • Anhui Provincial Hospital
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China, 100853
      • Chinese PLA General Hospital
    • Beijing, Beijing, China, 100730
      • Beijing Hospital
    • Beijing, Beijing, China, 100021
      • Cancer Hospital Chinese Academy of Medical Sciences
  • Chongqing
    • Chongqing, Chongqing, China, 400010
      • The Second Affiliated Hospital of Chongqing Medical University
    • Chongqing, Chongqing, China, 404000
      • Chongqing Three Gorges Central Hospital
    • Chongqing, Chongqing, China, 400042
      • Daping Hospital, Third Military Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Cancer Hospital
    • Xiamen, Fujian, China, 361003
      • The First Affiliated Hospital of Xiamen University
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510030
      • Cancer Center of Guangzhou Medical University
    • Shantou, Guangdong, China, 515031
      • Cancer Hospital of Shantou University Medical College
  • Guangxi
    • Guilin, Guangxi, China, 541001
      • Affiliated Hospital of Guilin Medical University
    • Nanning, Guangxi, China, 530021
      • The Peoples Hospital of Guangxi Zhuang Autonomous Region
  • Guizhou
    • Guiyang, Guizhou, China, 550000
      • Guizhou Cancer Hospital
    • Zunyi, Guizhou, China, 563000
      • The Affiliated Hospital of Zunyi Medical College
  • Hainan
    • Haikou, Hainan, China, 570206
      • Hainan General Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450052
      • The First Affiliated Hospital of Zhengzhou University
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
    • Changsha, Hunan, China, 410004
      • Changsha Central Hospital
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University Branch Shizi
    • Xuzhou, Jiangsu, China, 221000
      • Xuzhou Central Hospital
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • The First Hospital of China Medical University
    • Shenyang, Liaoning, China, 110042
      • Liaoning Cancer Hospital and Institute
  • Shaanxi
    • Xian, Shaanxi, China, 710061
      • The First Affiliated Hospital of Xian Jiaotong University
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
    • Jinan, Shandong, China, 250000
      • Qilu Hospital of Shandong University
    • Jinan, Shandong, China, 250031
      • Jinan Military General Hospital
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital
    • Weifang, Shandong, China, 261000
      • Weifang Peoples Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai, China, 200030
      • Shanghai Chest Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital
  • Yunnan
    • Kunming, Yunnan, China, 650100
      • Yunnan Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China, 310003
      • The first Affiliated Hospital, Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China, 310009
      • Zhejiang University College of Medicine Second Affiliated Hospital
    • Hangzhou, Zhejiang, China, 310006
      • Hangzhou First Peoples Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-75 years old, male or female, signed informed consent form
2. Advanced NSCLC diagnosed by pathological or clinical physicians
3. Eastern Cooperative Oncology Group (ECOG) performance score ≤ 1
4. Participants must have ≥ 1 measurable lesion as defined per RECIST v1.1
5. Participants must have no prior systemic chemotherapy for advanced or metastatic NSCLC
6. Life expectancy ≥ 12 weeks
7. Participants must have adequate organ function
8. Male/female is willing to use a highly effective method of birth control

Exclusion Criteria:

1. Diagnosed with NSCLC but with epidermal growth factor receptor (EGFR)-sensitizing mutation or anaplastic lymphoma kinase (ALK) gene translocation
2. Received any approved systemic anticancer therapy within 28 days prior to the initiation of study treatment
3. Received prior treatment with EGFR inhibitors or ALK inhibitors
4. Received prior therapies targeting programmed cell death protein-1 (PD-1) or programmed cell death protein ligand-1 (PD-L1)
5. With history of interstitial lung disease, non-infectious pneumonitis or uncontrolled systemic diseases
6. Clinically significant pericardial effusion
7. Severe infections, active leptomeningeal disease or uncontrolled, untreated brain metastasis
8. Any major surgical procedure ≤ 28 days before randomization
9. Human immunodeficiency virus (HIV) infection
10. Participants with untreated hepatitis B or C virus (HBV/HCV)
11. Active autoimmune diseases or history of autoimmune diseases
12. History of allergic reactions to chemotherapy

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tislelizumab + Platinum + Pemetrexed; Tislelizumab 200 milligrams (mg) administered intravenously (IV) once every 3 weeks plus cisplatin 75 mg/m^2 or carboplatin area under the plasma or serum concentration-time curve (AUC) 5 once every 3 weeks for 4 to 6 cycles and pemetrexed 500 mg/m^2 once every 3 weeks until unacceptable toxicity or disease progression (each cycle is 21 days)	Drug: Carboplatin; Administered intravenously; Drug: Cisplatin; Administered intravenously; Drug: Pemetrexed; Administered intravenously; Drug: Tislelizumab; Administered intravenously; Other Names: BGB-A317; Tevimbra
Active Comparator: Platinum + Pemetrexed; Cisplatin 75 mg/m^2 or carboplatin AUC 5 once every 3 weeks for 4 to 6 cycles and pemetrexed 500 mg/m^2 administered IV once every 3 weeks until unacceptable toxicity or disease progression (each cycle is 21 days)	Drug: Carboplatin; Administered intravenously; Drug: Cisplatin; Administered intravenously; Drug: Pemetrexed; Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) Assessed by Independent Review Committee (IRC) Assessment	PFS is defined as the time from randomization until first documentation of progression or death from any cause, whichever occurs first, as assessed by the IRC per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Through primary analysis data cut-off date of 23JAN2020 (up to approximately 1 year and 6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) by IRC Assessment	ORR is defined as the percentage of participants with complete response (CR) or partial response (PR), as assessed by the IRC using RECIST v1.1.	Through study completion data cut-off date of 26APR2023 (up to approximately 4 years and 9 months)
Duration of Response (DOR) by IRC Assessment	DOR is defined as the time from the first occurrence of a documented objective response to the time of documented disease progression, or death from any cause, whichever comes first, as assessed by the IRC using RECIST v1.1 in participants with documented objective responses	Through study completion data cut-off date of 26APR2023 (up to approximately 4 years and 9 months)
Overall Survival (OS)	OS is defined as the time from randomization until the date of death due to any cause	Through study completion data cut-off date of 26APR2023 (up to approximately 4 years and 9 months)
PFS by Investigator Assessment	PFS is defined as the time from randomization until first objectively documented disease progression, or death from any cause, whichever occurs first, as assessed by the investigator per RECIST v1.1	Through study completion data cut-off date of 26APR2023 (up to approximately 4 years and 9 months)
ORR by Investigator Assessment	ORR is defined as the percentage of participants with CR or PR, as assessed by the investigator using RECIST v1.1	Through study completion data cut-off date of 26APR2023 (up to approximately 4 years and 9 months)
DOR by Investigator Assessment	DOR is defined as the time from the first occurrence of a documented objective response to the time of documented disease progression, or death from any cause, whichever comes first, as assessed by the investigator using RECIST v1.1 in participants with documented objective responses	Through study completion data cut-off date of 26APR2023 (up to approximately 4 years and 9 months)
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13)	Change from baseline in EORTC QLQ-CL13 scores for coughing, dyspnea, and chest pain . The EORTC QLQ-LC13 is a questionnaire that measures lung cancer-specific disease and treatment symptoms. It includes 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. A lower score indicates an improvement in symptoms.	Baseline to Cycle 5 (each cycle is 21 days)
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status	Change from baseline in EORTC QLQ-C30 Global Health Status/Quality of Life score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of participants with cancer. It includes global health status and quality of life questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes.	Baseline to Cycle 5 (each cycle is 21 days)
Number of Participants With Adverse Events	Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), which includes laboratory tests, physical exams, electrocardiogram results and vital signs, according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0	Through study completion data cut-off date of 26APR2023 (up to approximately 4 years and 9 months)
PFS by IRC Based on Programmed Death Ligand 1 (PD-L1) Expression	PFS is defined as the time from randomization until first documentation of progression or death from any cause, whichever occurs first, as assessed by the IRC per RECIST v1.1, based on PD-L1 expression in tumor cells	Through study completion data cut-off date of 26APR2023 (up to approximately 4 years and 9 months)

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Publications and helpful links

General Publications

• Lu S, Yu Y, Barnes G, Qiu X, Bao Y, Tang B. Examining the Impact of Tislelizumab Added to Chemotherapy on Health-Related Quality-of-Life Outcomes in Previously Untreated Patients With Nonsquamous Non-Small Cell Lung Cancer. Cancer J. 2022 Mar-Apr 01;28(2):96-104. doi: 10.1097/PPO.0000000000000583.
• Lu S, Wang J, Yu Y, Yu X, Hu Y, Ai X, Ma Z, Li X, Zhuang W, Liu Y, Li W, Cui J, Wang D, Liao W, Zhou J, Wang Z, Sun Y, Qiu X, Gao J, Bao Y, Liang L, Wang M. Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial. J Thorac Oncol. 2021 Sep;16(9):1512-1522. doi: 10.1016/j.jtho.2021.05.005. Epub 2021 May 23.

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2018
• Primary Completion (Actual): January 23, 2020
• Study Completion (Actual): April 26, 2023

Study Registration Dates

• First Submitted: August 16, 2018
• First Submitted That Met QC Criteria: September 7, 2018
• First Posted (Actual): September 10, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 2, 2025
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Pemetrexed; Tislelizumab; Carboplatin
• Other Study ID Numbers: BGB-A317-304; CTR20180032 (Registry Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No