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

Phase 3

Completed

• Conditions: Non-Small Cell Lung Cancer
• Interventions: Drug: Tislelizumab; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed

• Registration Number: NCT03663205
• Lead Sponsor: BeiGene

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2018-07-23
• Study First Submitted: 2018-08-16
• Study First Submitted QC: 2018-09-07
• Study First Posted: 2018-09-10
• Primary Completion: 2020-01-23
• Study Completion: 2023-04-26
• Results First Submitted: 2024-04-11
• Status Verified: 2024-09
• Results First Submitted QC: 2024-09-26
• Last Update Submitted: 2024-09-26
• Results First Posted: 2024-11-25
• Last Update Posted: 2024-11-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 334

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tislelizumab + Platinum + Pemetrexed	Tislelizumab	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)
Tislelizumab + Platinum + Pemetrexed	Cisplatin	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)
Tislelizumab + Platinum + Pemetrexed	Carboplatin	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)
Tislelizumab + Platinum + Pemetrexed	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)
Platinum + Pemetrexed	Cisplatin	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)
Platinum + Pemetrexed	Carboplatin	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)
Platinum + Pemetrexed	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)

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) Assessed by Independent Review Committee (IRC) Assessment	Through primary analysis data cut-off date of 23JAN2020 (up to approximately 1 year and 6 months)	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

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) by IRC Assessment	Through study completion data cut-off date of 26APR2023 (up to approximately 4 years and 9 months)	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.
Duration of Response (DOR) by IRC Assessment	Through study completion data cut-off date of 26APR2023 (up to approximately 4 years and 9 months)	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
Overall Survival (OS)	Through study completion data cut-off date of 26APR2023 (up to approximately 4 years and 9 months)	OS is defined as the time from randomization until the date of death due to any cause
PFS by Investigator Assessment	Through study completion data cut-off date of 26APR2023 (up to approximately 4 years and 9 months)	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
ORR by Investigator Assessment	Through study completion data cut-off date of 26APR2023 (up to approximately 4 years and 9 months)	ORR is defined as the percentage of participants with CR or PR, as assessed by the investigator using RECIST v1.1
DOR by Investigator Assessment	Through study completion data cut-off date of 26APR2023 (up to approximately 4 years and 9 months)	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
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13)	Baseline to Cycle 5 (each cycle is 21 days)	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.
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	Baseline to Cycle 5 (each cycle is 21 days)	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.
Number of Participants With Adverse Events	Through study completion data cut-off date of 26APR2023 (up to approximately 4 years and 9 months)	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
PFS by IRC Based on Programmed Death Ligand 1 (PD-L1) Expression	Through study completion data cut-off date of 26APR2023 (up to approximately 4 years and 9 months)	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

Trial Locations

Locations (47)

Daping Hospital, Third Military Medical University; 🇨🇳 Chongqing, Chongqing, China

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China

Yunnan Cancer Hospital; 🇨🇳 Kunming, Yunnan, China

Anhui Provincial Hospital; 🇨🇳 Hefei, Anhui, China

Beijing Hospital; 🇨🇳 Beijing, Beijing, China

Cancer Hospital Chinese Academy of Medical Sciences; 🇨🇳 Beijing, Beijing, China

Peking Union Medical College Hospital; 🇨🇳 Beijing, Beijing, China

Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China

Beijing Cancer Hospital; 🇨🇳 Beijing, Beijing, China

The second Affiliated Hospital of Chongqing Medical University; 🇨🇳 Chongqing, Chongqing, China

Chongqing Three Gorges Central Hospital; 🇨🇳 Chongqing, Chongqing, China

Fujian Provincial Cancer Hospital; 🇨🇳 Fuzhou, Fujian, China

The First Affiliated Hospital of Xiamen University; 🇨🇳 Xiamen, Fujian, China

Cancer Hospital Of Shantou University Medical College; 🇨🇳 Shantou, Guangdong, China

Affiliated Hospital of Guilin Medical University; 🇨🇳 Guilin, Guangxi, China

The People's Hospital Of Guangxi Zhuang Autonomous Region; 🇨🇳 Nanning, Guangxi, China

Cancer Center of Guangzhou Medical University; 🇨🇳 Guangzhou, Guangzhou, China

Nanfang Hospital,Southern Medical University; 🇨🇳 Guangzhou, Guangzhou, China

Guizhou Cancer Hospital; 🇨🇳 Guiyang, Guizhou, China

Affiliated Hospital of Zunyi Medical College; 🇨🇳 Zunyi, Guizhou, China

Hainan General Hospital; 🇨🇳 Haikou, Hainan, China

Harbin Medical University Cancer Hospital; 🇨🇳 Harbin, Heilongjiang, China

Henan Cancer Hospital; 🇨🇳 Zhengzhou, Henan, China

the First Affiliated Hospital of Zhengzhou University; 🇨🇳 Zhengzhou, Henan, China

Hubei Cancer Hospital; 🇨🇳 Wuhan, Hubei, China

Hunan Cancer Hospital; 🇨🇳 Changsha, Hunan, China

Changsha Central Hospital; 🇨🇳 Changsha, Hunan, China

The First Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China

Xuzhou Central Hospital; 🇨🇳 Xuzhou, Jiangsu, China

The First Hospital of Jilin University; 🇨🇳 Changchun, Jilin, China

The First Hospital of China Medical University; 🇨🇳 Shenyang, Liaoning, China

Liaoning Cancer Hospital; 🇨🇳 Shenyang, Liaoning, China

Weifang People's Hospital; 🇨🇳 Huaifang, Shandong, China

Qilu Hospital of Shandong University; 🇨🇳 Jinan, Shandong, China

Jinan Central Hospital; 🇨🇳 Jinan, Shandong, China

Jinan Military General Hospital; 🇨🇳 Jinan, Shandong, China

Shandong Cancer Hospital; 🇨🇳 Jinan, Shandong, China

Shanghai Chest Hospital; 🇨🇳 Shanghai, Shanghai, China

The First Affiliated Hospital of Xi'an Jiaotong University; 🇨🇳 Xi'an, Shanxi, China

West China Hospital,Sichuan University; 🇨🇳 Chengdu, Sichuan, China

General Hospital, Tianjin Medical University; 🇨🇳 Tianjin, Tianjin, China

Tianjin Medical University Cancer Institute & Hospital; 🇨🇳 Tianjin, Tianjin, China

The First Affiliated Hospital of Medical School of Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China

Hangzhou First People's Hospital; 🇨🇳 Hangzhou, Zhejiang, China

The Second Affiliated Hospital of Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China

Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China

Zhejiang Cancer Hospital; 🇨🇳 Hangzhou, Zhejiang, China