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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03663205

Enrollment

334

Registered

2018-09-10

Start date

2018-07-23

Completion date

2023-04-26

Last updated

2025-02-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Non-Small Cell Lung Cancer

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).

Interventions

DRUGTislelizumab

Administered intravenously

DRUGCisplatin

Administered intravenously

DRUGCarboplatin

Administered intravenously

DRUGPemetrexed

Administered intravenously

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

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/

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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
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.
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
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

Countries

China

Participant flow

Recruitment details

This study was conducted at 47 study centers in China.

Participants by arm

Arm	Count
Tislelizumab + Platinum + Pemetrexed Tislelizumab 200 mg administered IV once every 3 weeks plus cisplatin 75 mg/m\^2 or carboplatin 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)	223
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)	111
Total	334

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	144	69
Overall Study	Lost to Follow-up	7	9
Overall Study	Sponsor decision	53	19
Overall Study	Transferred to long term extension study	11	3
Overall Study	Withdrawal by Subject	8	11

Baseline characteristics

Characteristic	Tislelizumab + Platinum + Pemetrexed	Platinum + Pemetrexed	Total
Age, Continuous	61.0 Years	62.0 Years	61.0 Years
PD-L1 Expression in Tumor Cells <1%	91 Participants	48 Participants	139 Participants
PD-L1 Expression in Tumor Cells 1%-49%	53 Participants	27 Participants	80 Participants
PD-L1 Expression in Tumor Cells ≥ 50%	74 Participants	36 Participants	110 Participants
PD-L1 Expression in Tumor Cells Unevaluable	5 Participants	0 Participants	5 Participants
Race/Ethnicity, Customized Asian	223 Participants	111 Participants	334 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	223 Participants	111 Participants	334 Participants
Sex: Female, Male Female	55 Participants	32 Participants	87 Participants
Sex: Female, Male Male	168 Participants	79 Participants	247 Participants
Smoking Status Current	32 Participants	13 Participants	45 Participants
Smoking Status Former	115 Participants	53 Participants	168 Participants
Smoking Status Never	76 Participants	45 Participants	121 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	144 / 223	69 / 111
other Total, other adverse events	222 / 222	109 / 110
serious Total, serious adverse events	99 / 222	25 / 110

Outcome results

Primary

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

Time frame: Through primary analysis data cut-off date of 23JAN2020 (up to approximately 1 year and 6 months)

Population: ITT analysis set included all randomized participants

Arm	Measure	Value (MEDIAN)
Tislelizumab + Platinum + Pemetrexed	Progression Free Survival (PFS) Assessed by Independent Review Committee (IRC) Assessment	9.7 Months
Platinum + Pemetrexed	Progression Free Survival (PFS) Assessed by Independent Review Committee (IRC) Assessment	7.6 Months

p-value: 0.005495% CI: [0.465, 0.912]One-sided, Log Rank Test

Secondary

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.

Time frame: Baseline to Cycle 5 (each cycle is 21 days)

Population: HRQoL analysis set included all randomized participants who received at least 1 dose of study drug and completed at least 1 HRQoL assessment

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Tislelizumab + Platinum + Pemetrexed	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	0.9 Score on a scale
Platinum + Pemetrexed	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	-3.0 Score on a scale

Comparison: Least squares mean difference in Global Health Status/Quality of Life score95% CI: [-0.9, 8.7]

Secondary

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.

Time frame: Baseline to Cycle 5 (each cycle is 21 days)

Population: Health-related quality of life (HRQoL) analysis set included all randomized participants who received at least 1 dose of study drug and completed at least 1 HRQoL assessment

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Tislelizumab + Platinum + Pemetrexed	Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13)	Coughing	-13.0 Score on a scale
Tislelizumab + Platinum + Pemetrexed	Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13)	Dyspnea	-1.4 Score on a scale
Tislelizumab + Platinum + Pemetrexed	Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13)	Chest Pain	-7.4 Score on a scale
Platinum + Pemetrexed	Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13)	Coughing	-10.8 Score on a scale
Platinum + Pemetrexed	Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13)	Dyspnea	-0.3 Score on a scale
Platinum + Pemetrexed	Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13)	Chest Pain	-4.2 Score on a scale

Comparison: Least squares mean difference in coughing score95% CI: [-7.4, 3.1]

Comparison: Least squares mean difference in dyspnea score95% CI: [-4.4, 2.1]

Comparison: Least squares mean difference in chest pain score95% CI: [-7.6, 1.2]

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, or death from any cause, whichever comes first, as assessed by the investigator using RECIST v1.1 in participants with documented objective responses