Study of Platinum Plus Etoposide With or Without BGB-A317 in Participants With Untreated Extensive-Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, multicenter, Phase 3 study to compare the efficacy of tislelizumab + cisplatin or carboplatin + etoposide (Arm A) and placebo + cisplatin or carboplatin + etoposide (Arm B) as first-line treatment in approximately 455 participants who have previously untreated extensive-stage small cell lung cancer (ES-SCLC)

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Platinum Plus Etoposide With or Without Tislelizumab (BGB-A317) in Patients With Untreated Extensive-Stage Small Cell Lung Cancer

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Tislelizumab, Carboplatin /Cisplatin, Etoposide
* Drug: Carboplatin / Cisplatin, Etoposide


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Age≥18 years old, male or female, signed Informed Consent Form (ICF). Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Histologically or cytologically confirmed ES-SCLC No prior systemic treatment for ES-SCLC Adequate hematologic and end organ function Key Exclusion Criteria: Active leptomeningeal disease or uncontrolled, untreated brain metastasis; Prior therapy with an antibody or drug against immune checkpoint pathways, including but not limited to, anti program death receptor-1 (anti-PD-1), anti-PD-L1, or anti cytotoxic T lymphocyte associated antigen 4 (anti CTLA-4) antibody; Was administered a live vaccine ≤ 4 weeks before randomization; Active autoimmune diseases or history of autoimmune diseases that may relapse Any condition that required systemic treatment with either corticosteroids or other immunosuppressive medication ≤ 14 days before randomization; With a history of interstitial lung disease, non-infectious pneumonitis, or uncontrolled systemic diseases; Severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy within 2 weeks prior to randomization, including but not limited to tuberculosis infection; Participant with untreated hepatitis B virus (HBV)/hepatitis C virus (HCV), or a known history of HIV infection; Participants with toxicities (as a result of prior anticancer therapy) which have not recovered to baseline or stabilized at the time of randomization; Clinically significant pericardial effusion, or Clinically uncontrolled pleural effusion NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tislelizumab plus etoposide and platinum<br> | Drug: Tislelizumab, Carboplatin /Cisplatin, Etoposide<br>* Tislelizumab (200 mg IV Q3W) in combination with chemotherapy consisting of etoposide (100 mg/m² IV Days 1-3 of each 21-day cycle) and platinum (cisplatin 75 mg/m² IV Q3W or carboplatin area under the plasma or serum concentration-time curve (AUC) 5 IV Q3W) for 4 cycles. Then maintenance consists of Tislelizumab Q3W and will continue until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of informed consent.<br>|
| Active Comparator: Placebo plus etoposide and platinum<br> | Drug: Carboplatin / Cisplatin, Etoposide<br>* Placebo Q3W in combination with chemotherapy consisting of etoposide (100 mg/m² IV Days 1-3 of each 21-day cycle) and platinum (cisplatin 75 mg/m² IV Q3W or carboplatin AUC 5 IV Q3W) for 4 cycles. Then maintenance consists of Placebo Q3W and will continue until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of informed consent.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | To evaluate and compare the efficacy of tislelizumab + cisplatin or carboplatin + etoposide compared with placebo + cisplatin or carboplatin + etoposide in the intent to treat Analysis Set as measured by overall survival (OS) | Baseline until death from any cause (up to approximately 51 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | To evaluate and compare the efficacy of tislelizumab + cisplatin or carboplatin + etoposide compared with placebo + cisplatin or carboplatin + etoposide in the ITT Analysis Set as measured by investigator assessed overall response rate (ORR), according to RECIST v1.1 | Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 29 months) | 
| Duration Of Response (DOR) | To evaluate and compare the efficacy of tislelizumab + cisplatin or carboplatin + etoposide compared with placebo + cisplatin or carboplatin + etoposide in the ITT Analysis Set as measured by investigator assessed duration of response (DOR) according to RECIST v1.1 | Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 29 months) | 
| Disease Control Rate (DCR) | To evaluate and compare the efficacy of tislelizumab + cisplatin or carboplatin + etoposide compared with placebo + cisplatin or carboplatin + etoposide in the ITT Analysis Set as measured by investigator assessed disease control rate (DCR) according to RECIST v1.1 | up to approximately 29 months | 
| Incidence and severity of treatment-emergent adverse events (TEAEs) graded according to National Cancer Institute Common Terminology Criteria for Adverse Events |  | up to approximately 51 months | 
| Percentage of patients with clinically meaningful changes post baseline |  | up to approximately 29 | 
| Time to deterioration (TTD), defined as the time from randomization to the first occurrence of worsening scores confirmed at the following visit or death from any cause |  | up to approximately 29 months | 
| Progression Free Survival (PFS) | To evaluate and compare the efficacy of tislelizumab + cisplatin or carboplatin + etoposide compared with placebo + cisplatin or carboplatin + etoposide in the intent to treat (ITT) Analysis Set as measured by investigator assessed progression free survival (PFS) according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Baseline until PD or death, whichever occurs first (up to approximately 29 months) |