Non-Small Cell Lung Cancer
Conditions
Brief 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).
Interventions
DRUGTislelizumab
Administered intravenously as described
DRUGPaclitaxel
Administered intravenously as described
DRUGNab-paclitaxel
Administered intravenously as described
DRUGCarboplatin
Administered intravenously as described
Sponsors
BeiGene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) by Independent Review Committee (IRC) Assessment as of Data Cut-off Date of 06DEC2019 | Through primary analysis data cut-off date of 06DEC2019 (up to approximately 1 year and 4 months) | 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 |
| PFS by IRC Assessment as of Data Cut-off Date of 30SEP2020 | Through primary analysis data cut-off date of 30SEP2020 (up to approximately 2 years and 2 months) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR by Investigator Assessment | Through study completion data cut-off date of 28APR2023 (up to approximately 4 years and 9 months) | 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. |
| Duration of Response (DOR) by IRC Assessment | Through study completion data cut-off date of 28APR2023 (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 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. |
| DOR by Investigator Assessment | Through study completion data cut-off date of 28APR2023 (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 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. |
| PFS by Investigator Assessment | Through study completion data cut-off date of 28APR2023 (up to approximately 4 years and 9 months) | 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 |
| Overall Survival (OS) | Through study completion data cut-off date of 28APR2023 (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 |
| 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 | 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. |
| 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 | 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. |
| Number of Participants With Adverse Events | From first dose to 30 days after the last dose (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 28APR2023 (up to approximately 4 years and 9 months) | 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 |
| Objective Response Rate (ORR) by IRC Assessment | Through study completion data cut-off date of 28APR2023 (up to approximately 4 years and 9 months) | 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. |
Countries
China
Participant flow
Recruitment details
This study was conducted at multiple study centers in China. Data are presented as of the study completion data cut-off date of 28APR2023.
Participants by arm
| Arm | Count |
|---|---|
| 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) | 120 |
| 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) | 119 |
| 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) | 121 |
| Total | 360 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 78 | 86 | 87 |
| Overall Study | Did not meet inclusion criteria | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 4 | 1 | 1 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Sponsor decision | 23 | 17 | 16 |
| Overall Study | Transfer to long term extension study | 10 | 12 | 5 |
| Overall Study | Withdrawal by Subject | 5 | 2 | 11 |
Baseline characteristics
| Characteristic | Tislelizumab + Paclitaxel + Carboplatin | Tislelizumab + Nab-paclitaxel + Carboplatin | Paclitaxel + Carboplatin | Total |
|---|---|---|---|---|
| Age, Continuous | 60.0 Years | 64.0 Years | 63.0 Years | 62.5 Years |
| Race/Ethnicity, Customized Asian | 120 Participants | 119 Participants | 121 Participants | 360 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 120 Participants | 119 Participants | 121 Participants | 360 Participants |
| Sex: Female, Male Female | 13 Participants | 7 Participants | 10 Participants | 30 Participants |
| Sex: Female, Male Male | 107 Participants | 112 Participants | 111 Participants | 330 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 78 / 120 | 86 / 119 | 87 / 121 |
| other Total, other adverse events | 119 / 120 | 117 / 118 | 116 / 117 |
| serious Total, serious adverse events | 56 / 120 | 55 / 118 | 29 / 117 |
Outcome results
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
Time frame: Through primary analysis data cut-off date of 30SEP2020 (up to approximately 2 years and 2 months)
Population: ITT analysis set included all participants who were randomized
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tislelizumab + Paclitaxel + Carboplatin | PFS by IRC Assessment as of Data Cut-off Date of 30SEP2020 | 7.7 Months |
| Tislelizumab + Nab-paclitaxel + Carboplatin | PFS by IRC Assessment as of Data Cut-off Date of 30SEP2020 | 9.6 Months |
| Paclitaxel + Carboplatin | PFS by IRC Assessment as of Data Cut-off Date of 30SEP2020 | 5.5 Months |
95% CI: [0.32, 0.61]
95% CI: [0.3, 0.59]
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
Time frame: Through primary analysis data cut-off date of 06DEC2019 (up to approximately 1 year and 4 months)
Population: ITT analysis set included all participants who were randomized
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tislelizumab + Paclitaxel + Carboplatin | Progression Free Survival (PFS) by Independent Review Committee (IRC) Assessment as of Data Cut-off Date of 06DEC2019 | 7.6 Months |
| Tislelizumab + Nab-paclitaxel + Carboplatin | Progression Free Survival (PFS) by Independent Review Committee (IRC) Assessment as of Data Cut-off Date of 06DEC2019 | 7.6 Months |
| Paclitaxel + Carboplatin | Progression Free Survival (PFS) by Independent Review Committee (IRC) Assessment as of Data Cut-off Date of 06DEC2019 | 5.5 Months |
p-value: 0.000195% CI: [0.37, 0.74]One-sided stratified log-rank test
p-value: <0.000195% CI: [0.33, 0.67]One-sided stratified log-rank test
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.
Time frame: Through study completion data cut-off date of 28APR2023 (up to approximately 4 years and 9 months)
Population: ITT analysis set included all participants who were randomized
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tislelizumab + Paclitaxel + Carboplatin | DOR by Investigator Assessment | 10.6 Months |
| Tislelizumab + Nab-paclitaxel + Carboplatin | DOR by Investigator Assessment | 8.8 Months |
| Paclitaxel + Carboplatin | DOR by Investigator Assessment | 4.8 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.
Time frame: Through study completion data cut-off date of 28APR2023 (up to approximately 4 years and 9 months)
Population: ITT analysis set included all participants who were randomized
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tislelizumab + Paclitaxel + Carboplatin | Duration of Response (DOR) by IRC Assessment | 8.4 Months |
| Tislelizumab + Nab-paclitaxel + Carboplatin | Duration of Response (DOR) by IRC Assessment | 8.6 Months |
| Paclitaxel + Carboplatin | Duration of Response (DOR) by IRC Assessment | 4.3 Months |
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.
Time frame: Baseline to Cycle 5; each cycle is 21 days
Population: HRQoL analysis set included all randomized participants who received ≥ 1 dose of study drug and completed ≥ HRQoL assessment post baseline
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Tislelizumab + Paclitaxel + Carboplatin | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status | 2.4 Score on a scale |
| Tislelizumab + Nab-paclitaxel + Carboplatin | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status | 3.3 Score on a scale |
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.
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 ≥ 1 dose of study drug and completed ≥ HRQoL assessment post baseline
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Tislelizumab + Paclitaxel + Carboplatin | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13) | Chest pain | 0.4 Score on a scale |
| Tislelizumab + Paclitaxel + Carboplatin | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13) | Coughing | -7.0 Score on a scale |
| Tislelizumab + Paclitaxel + Carboplatin | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13) | Dyspnea | -2.7 Score on a scale |
| Tislelizumab + Nab-paclitaxel + Carboplatin | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13) | Dyspnea | -1.0 Score on a scale |
| Tislelizumab + Nab-paclitaxel + Carboplatin | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13) | Chest pain | -0.4 Score on a scale |
| Tislelizumab + Nab-paclitaxel + Carboplatin | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13) | Coughing | -0.4 Score on a scale |
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
Time frame: From first dose to 30 days after the last dose (up to approximately 4 years and 9 months)
Population: Safety analysis set included all randomized participants who received ≥ 1 dose of any study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tislelizumab + Paclitaxel + Carboplatin | Number of Participants With Adverse Events | At least 1 TEAE | 120 Participants |
| Tislelizumab + Paclitaxel + Carboplatin | Number of Participants With Adverse Events | At least 1 SAE | 56 Participants |
| Tislelizumab + Nab-paclitaxel + Carboplatin | Number of Participants With Adverse Events | At least 1 TEAE | 117 Participants |
| Tislelizumab + Nab-paclitaxel + Carboplatin | Number of Participants With Adverse Events | At least 1 SAE | 55 Participants |
| Paclitaxel + Carboplatin | Number of Participants With Adverse Events | At least 1 TEAE | 117 Participants |
| Paclitaxel + Carboplatin | Number of Participants With Adverse Events | At least 1 SAE | 29 Participants |
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.
Time frame: Through study completion data cut-off date of 28APR2023 (up to approximately 4 years and 9 months)
Population: ITT analysis set included all participants who were randomized
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tislelizumab + Paclitaxel + Carboplatin | Objective Response Rate (ORR) by IRC Assessment | 74.2 Percentage of participants |
| Tislelizumab + Nab-paclitaxel + Carboplatin | Objective Response Rate (ORR) by IRC Assessment | 73.9 Percentage of participants |
| Paclitaxel + Carboplatin | Objective Response Rate (ORR) by IRC Assessment | 47.9 Percentage of participants |
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.
Time frame: Through study completion data cut-off date of 28APR2023 (up to approximately 4 years and 9 months)
Population: ITT analysis set included all participants who were randomized
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tislelizumab + Paclitaxel + Carboplatin | ORR by Investigator Assessment | 70.0 Percentage of participants |
| Tislelizumab + Nab-paclitaxel + Carboplatin | ORR by Investigator Assessment | 78.2 Percentage of participants |
| Paclitaxel + Carboplatin | ORR by Investigator Assessment | 49.6 Percentage of participants |
Secondary
Overall Survival (OS)
OS is defined as the time from randomization until the date of death due to any cause
Time frame: Through study completion data cut-off date of 28APR2023 (up to approximately 4 years and 9 months)
Population: ITT analysis set included all participants who were randomized
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tislelizumab + Paclitaxel + Carboplatin | Overall Survival (OS) | 26.1 Months |
| Tislelizumab + Nab-paclitaxel + Carboplatin | Overall Survival (OS) | 23.3 Months |
| Paclitaxel + Carboplatin | Overall Survival (OS) | 19.4 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
Time frame: Through study completion data cut-off date of 28APR2023 (up to approximately 4 years and 9 months)
Population: ITT analysis set included all participants who were randomized
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tislelizumab + Paclitaxel + Carboplatin | PFS by Investigator Assessment | 9.6 Months |
| Tislelizumab + Nab-paclitaxel + Carboplatin | PFS by Investigator Assessment | 9.8 Months |
| Paclitaxel + Carboplatin | PFS by Investigator Assessment | 5.5 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
Time frame: Through study completion data cut-off date of 28APR2023 (up to approximately 4 years and 9 months)
Population: ITT analysis set included all participants who were randomized; participants evaluable for PD-L1 expression were included
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tislelizumab + Paclitaxel + Carboplatin | PFS by IRC Based on Programmed Death Ligand 1 (PD-L1) Expression | PD-L Expression (<1%) | 7.6 Months |
| Tislelizumab + Paclitaxel + Carboplatin | PFS by IRC Based on Programmed Death Ligand 1 (PD-L1) Expression | PD-L Expression (≥ 50%) | 7.7 Months |
| Tislelizumab + Paclitaxel + Carboplatin | PFS by IRC Based on Programmed Death Ligand 1 (PD-L1) Expression | PD-L Expression (1% to 49%) | 9.9 Months |
| Tislelizumab + Nab-paclitaxel + Carboplatin | PFS by IRC Based on Programmed Death Ligand 1 (PD-L1) Expression | PD-L Expression (<1%) | 7.6 Months |
| Tislelizumab + Nab-paclitaxel + Carboplatin | PFS by IRC Based on Programmed Death Ligand 1 (PD-L1) Expression | PD-L Expression (≥ 50%) | 9.7 Months |
| Tislelizumab + Nab-paclitaxel + Carboplatin | PFS by IRC Based on Programmed Death Ligand 1 (PD-L1) Expression | PD-L Expression (1% to 49%) | 9.8 Months |
| Paclitaxel + Carboplatin | PFS by IRC Based on Programmed Death Ligand 1 (PD-L1) Expression | PD-L Expression (≥ 50%) | 5.5 Months |
| Paclitaxel + Carboplatin | PFS by IRC Based on Programmed Death Ligand 1 (PD-L1) Expression | PD-L Expression (1% to 49%) | 5.0 Months |
| Paclitaxel + Carboplatin | PFS by IRC Based on Programmed Death Ligand 1 (PD-L1) Expression | PD-L Expression (<1%) | 5.5 Months |