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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Tislelizumab
* Drug: Paclitaxel
* Drug: Nab-paclitaxel
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Age 18-75 years old, male or female, and signed informed consent form (ICF) Advanced NSCLC diagnosed by pathological or clinical physicians Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1 Participants must have ≥ 1 measurable lesion as defined per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Must be treatment-naive for locally advanced or metastatic squamous NSCLC Life expectancy ≥ 12 weeks Participants must have adequate organ function Male/Female is willing to use a highly effective method of birth control Key Exclusion Criteria: Diagnosed with NSCLC but with epidermal growth factor receptors (EGFR)-sensitizing mutation or anaplastic lymphoma kinase (ALK) gene translocation Received any approved systemic anticancer therapy Received prior treatment with EGFR inhibitors or ALK inhibitors Received prior therapies targeting programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) With history of interstitial lung disease Clinically significant pericardial effusion Severe infections, active leptomeningeal disease or uncontrolled, untreated brain metastasis Any major surgical procedure before randomization Human immunodeficiency virus infection Untreated hepatitis B virus (HBV)/hepatitis C virus (HCV) Active autoimmune diseases or history of autoimmune diseases History of allergic reactions to chemotherapy NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tislelizumab + Paclitaxel + Carboplatin<br>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<br>* Administered intravenously as described<br>* Other names: BGB-A317;Drug: Paclitaxel<br>* Administered intravenously as described<br>Drug: Carboplatin<br>* Administered intravenously as described<br>|
| Experimental: Tislelizumab + Nab-paclitaxel + Carboplatin<br>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<br>* Administered intravenously as described<br>* Other names: BGB-A317;Drug: Nab-paclitaxel<br>* Administered intravenously as described<br>Drug: Carboplatin<br>* Administered intravenously as described<br>|
| Active Comparator: Paclitaxel + Carboplatin<br>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<br>* Administered intravenously as described<br>Drug: Carboplatin<br>* Administered intravenously as described<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) 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 | Up to approximately 2 years and 2 months; data presented as of primary analysis data cut off date of 30SEP2020 | 

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 | Up to approximately 2 years and 2 months | 
| Objective Response Rate (ORR) by IRC and Investigator Assessment | ORR is defined as the percentage of participants with complete response (CR) and partial response (PR), as assessed by the IRC and investigator using RECIST v1.1. | Up to approximately 2 years and 2 months | 
| Duration of Response (DOR) by IRC and Investigator Assessment | DOR is defined as the time from the first occurrence of a documented objective response to the time of relapse or death from any cause, whichever comes first, as assessed by the IRC and the investigator using RECIST v1.1 in all randomized participants with documented objective responses. | Up to approximately 2 years and 2 months | 
| Progression-free Survival (PFS) by Investigator 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 investigator per RECIST v1.1 | Up to approximately 2 years and 2 months | 
| PFS Based on Programmed Death Ligand 1 (PD-L1) Expression | 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 investigator per RECIST v1.1 based on PD-L1 expression | Up to approximately 2 years and 2 months | 
| European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13) | Mean change from baseline in EORTC QLQ-CL13 scores for dyspnea, cough, 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. | Baseline to Cycle 5; up to approximately 2 years and 2 months; 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 | Mean 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 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; up to approximately 2 years and 2 months; 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 | Up to approximately 4 years and 3 months |