A Study of Tislelizumab in Combination With Chemotherapy Versus Chemotherapy in Advanced Lung Cancer

A Phase 3, Multicenter, Randomized Open-Label Study to Compare the Efficacy and Safety of Tislelizumab (BGB A317, Anti-PD1 Antibody) Combined With Paclitaxel Plus Carboplatin or Nab Paclitaxel Plus Carboplatin Versus Paclitaxel Plus Carboplatin Alone as First-Line Treatment for Untreated Advanced Squamous Non-small Cell Lung Cancer

An open-label, randomized, multicenter Phase 3 study designed to compare the efficacy and safety of tislelizumab combined with chemotherapy versus chemotherapy only as first-line treatment in advanced squamous non-small cell lung cancer (NSCLC).

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Tislelizumab; Drug: Paclitaxel; Drug: Carboplatin; Drug: Nab-paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 360
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230001
      • Anhui Provincial Hospital
    • Hefei, Anhui, China, 230022
      • The First Affiliated Hospital of Anhui Medical University
  • 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
    • Beijing, Beijing, China, 101149
      • Beijing Chest Hospital,Capital Medical University
  • Chongqing
    • Chongqing, Chongqing, China, 400010
      • The Second Affiliated Hospital of Chongqing Medical University
    • Chongqing, Chongqing, China, 400038
      • The First Hospital Affiliated to AMU (Southwest Hospital)
    • Chongqing, Chongqing, China, 400042
      • Daping Hospital of The 3rd Military University
    • Chongqing, Chongqing, China, 404000
      • Chongqing Sanxia Central Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Tumor 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, 528400
      • Cancer Center of Guangzhou Medical University
    • Shantou, Guangdong, China, 515031
      • Cancer Hospital of Shantou University Medical College
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • The People's Hospital of Guangxi Zhuang Autonomous Region
  • Guizhou
    • Zunyi, Guizhou, China, 563099
      • Affiliated Hospital of Zunyi Medical College
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
    • Zhengzhou, Henan, China, 450052
      • The First Affiliated Hospital, Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
    • Wuhan, Hubei, China, 430022
      • Union Hospital Tongji Medical College Huazhong University of science and Technology
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
    • Changsha, Hunan, China, 410011
      • 2nd Hospital of Central South University
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital
    • Nanjing, Jiangsu, China, 210002
      • Nanjing General Hospital
    • Suzhou, Jiangsu, China, 215004
      • The First Affiliated Hospital Of Soochow University
    • Xuzhou, Jiangsu, China, 221009
      • Xuzhou Central Hospital
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Liaoning Cancer Hospital & Institute
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
    • Jinan, Shandong, China
      • Qilu Hospital of Shandong University
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital
    • Jinan, Shandong, China, 250031
      • The 96th Hospital of the Joint Service Support Force of the People's Liberation Army of China
    • Weifang, Shandong, China, 261041
      • Weifang People's Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Shanghai Chest Hospital
  • Shanxi
    • Xi'an, Shanxi, China, 710061
      • The First Affiliated Hospital Of Xi'an Jiaotong University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute & Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
    • Hangzhou, Zhejiang, China, 310002
      • Hangzhou First People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Age 18-75 years old, male or female, and signed informed consent form (ICF)
2. Advanced NSCLC diagnosed by pathological or clinical physicians
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1
4. Participants must have ≥ 1 measurable lesion as defined per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
5. Must be treatment-naive for locally advanced or metastatic squamous 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

Key Exclusion Criteria:

1. Diagnosed with NSCLC but with epidermal growth factor receptors (EGFR)-sensitizing mutation or anaplastic lymphoma kinase (ALK) gene translocation
2. Received any approved systemic anticancer therapy
3. Received prior treatment with EGFR inhibitors or ALK inhibitors
4. Received prior therapies targeting programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1)
5. With history of interstitial lung disease
6. Clinically significant pericardial effusion
7. Severe infections, active leptomeningeal disease or uncontrolled, untreated brain metastasis
8. Any major surgical procedure before randomization
9. Human immunodeficiency virus infection
10. Untreated hepatitis B virus (HBV)/hepatitis C virus (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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tislelizumab + Paclitaxel + Carboplatin; Tislelizumab 200 milligrams (mg) plus paclitaxel 175 mg/m^2 and carboplatin area under the plasma or serum concentration-time curve (AUC) 5 on Day 1 administered intravenously once every 3 weeks until unacceptable toxicity, withdrawal of consent, loss of clinical benefit, or disease progression; paclitaxel and carboplatin were administered for 4 to 6 cycles (each cycle is 21 days)	Drug: Tislelizumab; Administered intravenously as described; Other Names: BGB-A317; Tevimbra; Drug: Paclitaxel; Administered intravenously as described; Drug: Carboplatin; Administered intravenously as described
Experimental: Tislelizumab + Nab-paclitaxel + Carboplatin; Tislelizumab 200 mg on Day 1 plus Nab-paclitaxel 100 mg/m^2 on Days 1, 8, and 15 and carboplatin AUC 5 on Day 1 administered intravenously once every 3 weeks until unacceptable toxicity, withdrawal of consent, loss of clinical benefit, or disease progression; Nab-paclitaxel and carboplatin were administered for 4 to 6 cycles (each cycle is 21 days)	Drug: Tislelizumab; Administered intravenously as described; Other Names: BGB-A317; Tevimbra; Drug: Carboplatin; Administered intravenously as described; Drug: Nab-paclitaxel; Administered intravenously as described
Active Comparator: Paclitaxel + Carboplatin; Paclitaxel 175 mg/m^2 and carboplatin AUC 5 on Day 1 administered intravenously once every 3 weeks for 4 to 6 cycles (each cycle is 21 days)	Drug: Paclitaxel; Administered intravenously as described; Drug: Carboplatin; Administered intravenously as described

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) by Independent Review Committee (IRC) Assessment as of Data Cut-off Date of 06DEC2019	PFS is defined as the time from randomization until first documentation of disease progression as assessed by the IRC per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death from any cause, whichever occurs first	Through primary analysis data cut-off date of 06DEC2019 (up to approximately 1 year and 4 months)
PFS by IRC Assessment as of Data Cut-off Date of 30SEP2020	PFS is defined as the time from randomization until first documentation of disease progression as assessed by the IRC per RECIST v1.1 or death from any cause, whichever occurs first	Through primary analysis data cut-off date of 30SEP2020 (up to approximately 2 years and 2 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 28APR2023 (up to approximately 4 years and 9 months)
Objective Response Rate (ORR) by IRC Assessment	ORR is defined as the percentage of participants with complete response (CR) and partial response (PR), as assessed by the IRC using RECIST v1.1.	Through study completion data cut-off date of 28APR2023 (up to approximately 4 years and 9 months)
ORR by Investigator Assessment	ORR is defined as the percentage of participants with complete response (CR) and partial response (PR), as assessed by the investigator using RECIST v1.1.	Through study completion data cut-off date of 28APR2023 (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 assessed by the IRC using RECIST v1.1, or death from any cause, whichever comes first, in all randomized participants with documented objective responses. Data are based on number of responders.	Through study completion data cut-off date of 28APR2023 (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 assessed by the investigator using RECIST v1.1, or death from any cause, whichever comes first, in all randomized participants with documented objective responses. Data are based on number of responders.	Through study completion data cut-off date of 28APR2023 (up to approximately 4 years and 9 months)
PFS by Investigator Assessment	PFS is defined as the time from randomization until first documentation of disease progression as assessed by the investigator per RECIST v1.1 or death from any cause, whichever occurs first	Through study completion data cut-off date of 28APR2023 (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 disease progression as assessed by the IRC per RECIST v1.1 or death from any cause, whichever occurs first, based on PD-L1 expression in tumor cells	Through study completion data cut-off date of 28APR2023 (up to approximately 4 years and 9 months)
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13)	Least squares mean change from baseline in EORTC QLQ-CL13 scores for chest pain, coughing, and dyspnea between tislelizumab arms and paclitaxel + carboplatin arm. 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
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status	Least squares mean change from baseline in EORTC QLQ-C30 Global Health Status/Quality of Life score between tislelizumab arms and paclitaxel + carboplatin arm. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of cancer patients. 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	From first dose to 30 days after the last dose (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

• Wang J, Lu S, Yu X, Hu Y, Sun Y, Wang Z, Zhao J, Yu Y, Hu C, Yang K, Feng G, Ying K, Zhuang W, Zhou J, Wu J, Leaw SJ, Zhang J, Lin X, Liang L, Yang N. Tislelizumab Plus Chemotherapy vs Chemotherapy Alone as First-line Treatment for Advanced Squamous Non-Small-Cell Lung Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 May 1;7(5):709-717. doi: 10.1001/jamaoncol.2021.0366.
• Wang, J, S. Lu, et al. Randomized Phase III Study of Tislelizumab plus Chemotherapy versus Chemotherapy Alone as First-Line Treatment for Advanced Squamous Non-Small Cell Lung Cancer (Sq-NSCLC): RATIONALE-307 Updated Analysis. IOTECH Abstract, Vol. 16 Supplement 1, Dec. 2022. doi.org/10.1016/j.iotech.2022.100244.

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2018
• Primary Completion (Actual): September 30, 2020
• Study Completion (Actual): April 28, 2023

Study Registration Dates

• First Submitted: July 3, 2018
• First Submitted That Met QC Criteria: July 19, 2018
• First Posted (Actual): July 20, 2018

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Carboplatin; Paclitaxel; Albumin-Bound Paclitaxel; Tislelizumab
• Other Study ID Numbers: BGB-A317-307; CTR20180292 (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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes