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

Non-Small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03594747
• Other study ID #: BGB-A317-307
• Secondary ID: CTR20180292
• Status: Completed
• Phase: Phase 3
• Start date: July 30, 2018
• Est. completion date: April 28, 2023

Study information

• Verified date: February 2024
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 360
• Est. completion date: April 28, 2023
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Tislelizumab
Administered intravenously as described
• Paclitaxel
Administered intravenously as described
• Nab-paclitaxel
Administered intravenously as described
• Carboplatin
Administered intravenously as described

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Beijing Chest Hospital,Capital Medical University	Beijing	Beijing
China	Beijing Hospital	Beijing	Beijing
China	Cancer Hospital Chinese Academy of Medical Sciences	Beijing	Beijing
China	Chinese PLA General Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	The First Hospital of Jilin University	Changchun	Jilin
China	2nd Hospital of Central South University	Changsha	Hunan
China	Hunan Cancer Hospital	Changsha	Hunan
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	Chongqing Sanxia Central Hospital	Chongqing	Chongqing
China	Daping Hospital of The 3rd Military University	Chongqing	Chongqing
China	The First Hospital Affiliated to AMU (Southwest Hospital)	Chongqing	Chongqing
China	The Second Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Fujian Tumor Hospital	Fuzhou	Fujian
China	Cancer Center of Guangzhou Medical University	Guangzhou	Guangdong
China	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Hangzhou First People's Hospital	Hangzhou	Zhejiang
China	Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine	Hangzhou	Zhejiang
China	The First Affiliated Hospital, Zhejiang University	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	Jinan Central Hospital	Jinan	Shandong
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	Shandong Cancer Hospital	Jinan	Shandong
China	The 96th Hospital of the Joint Service Support Force of the People's Liberation Army of China	Jinan	Shandong
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Nanjing General Hospital	Nanjing	Jiangsu
China	The People's Hospital of Guangxi Zhuang Autonomous Region	Nanning	Guangxi
China	Shanghai Chest Hospital	Shanghai	Shanghai
China	Cancer Hospital of Shantou University Medical College	Shantou	Guangdong
China	Liaoning Cancer Hospital & Institute	Shenyang	Liaoning
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
China	Weifang People's Hospital	Weifang	Shandong
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	Xuzhou Central Hospital	Xuzhou	Jiangsu
China	Henan Cancer Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital, Zhengzhou University	Zhengzhou	Henan
China	Affiliated Hospital of Zunyi Medical College	Zunyi	Guizhou

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Country where clinical trial is conducted

China, 

References & Publications (2)

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. — View Citation

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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)