Study of Tislelizumab in Combination With Chemotherapy Compared to Chemotherapy Alone for Participants With Urothelial Carcinoma

Study Overview
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Brief Summary
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This is a multicenter, randomized, double-blind, placebo-controlled, Phase 3 study designed to compare the efficacy and safety of tislelizumab + either cisplatin or carboplatin + gemcitabine versus placebo+ either cisplatin or carboplatin + gemcitabine in approximately 420 participants with locally advanced or metastatic urothelial carcinoma who have not received prior systemic therapy.

Official Title
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A Phase 3, Multi-center, Randomized, Double-Blind, Placebo-Controlled Study of Either Cisplatin or Carboplatin +Gemcitabine + Tislelizumab Compared With Either Cisplatin or Carboplatin + Gemcitabine + Placebo as First-line Treatment for Patients With Locally Advanced or Metastatic Urothelial Carcinoma

Conditions
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Urothelial Carcinoma

Intervention / Treatment
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* Drug: Tislelizumab
* Drug: Placebo
* Drug: Cisplatin
* Drug: Gemcitabine Hydrochloride
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female aged 18 to 75 years on the day of signing the Informed Consent Form (ICF) Histologically confirmed, inoperable, locally advanced, or metastatic urothelial cancer (UC) Must be eligible to receive cisplatin or carboplatin in the investigator's judgment Have had no prior systemic chemotherapy for locally advanced or metastatic UC Must be able to provide fresh or archival tumor tissues with an associated pathological report. Must have evaluable disease (either measurable or non-measurable) as defined per RECIST v1.1. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1. Adequate organ function before randomization: Key Exclusion Criteria: Received prior therapies targeting PD-1, PD-L1, PD-L2, CTLA4, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. Any approved anticancer therapy within 28 days before randomization. Active leptomeningeal disease or uncontrolled, untreated brain metastasis Participants with uncontrolled hypercalcemia Participants with active autoimmune diseases or history of autoimmune diseases that may relapse History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled diseases A known history of HIV infection. Prior allogeneic stem cell transplantation or organ transplantation. History of severe hypersensitivity reactions to other monoclonal antibodies. 10．History of allergic reactions to cisplatin, carboplatin, or other platinum-containing compounds. 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tislelizumab in combination with chemotherapy<br>Tislelizumab: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles | Drug: Tislelizumab<br>* 200 mg administered Intravenously (IV) as specified in the treatment arm<br>* Other names: BGB-A317;Drug: Cisplatin<br>* 70 mg/m2 administered IV as specified in the treatment arm<br>Drug: Gemcitabine Hydrochloride<br>* 1000 mg/m2 administered IV as specified in the treatment arm<br>Drug: Carboplatin<br>* Area Under the Curve (AUC) 4.5 administered IV as specified in the treatment arm<br>|
| Placebo Comparator: Placebo in combination with chemotherapy<br>Placebo: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles | Drug: Placebo<br>* Tislelizumab placebo to match<br>Drug: Cisplatin<br>* 70 mg/m2 administered IV as specified in the treatment arm<br>Drug: Gemcitabine Hydrochloride<br>* 1000 mg/m2 administered IV as specified in the treatment arm<br>Drug: Carboplatin<br>* Area Under the Curve (AUC) 4.5 administered IV as specified in the treatment arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) in the Intent to Treat (ITT) set |  | From first randomization up to 3.5 years, approximately | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) per RECIST v1.1 in ITT | the proportion of participants who had Complete Response (CR) or Partial Response (PR) as assessed by the investigator per RECIST v1.1 in the ITT Analysis Set | From first randomization up to 3.5 years, approximately | 
| Duration of response (DOR) | the time from the first occurrence of a documented objective response to documented Progressive Disease (PD), or death from any cause, whichever occurs first, as determined by the investigator per RECIST v1.1 in the ITT Analysis Set | From first randomization up to 3.5 years, approximately | 
| Progression-free survival (PFS) | the time from randomization to the first objectively documented PD, or death from any cause, whichever occurs first, as determined by the investigator per RECIST v1.1 in the ITT Analysis Set | From first randomization up to 3.5 years, approximately | 
| Overall survival rate at 1 and 2 years for each treatment arm | the proportion of OS participants at 1 year and 2 years from randomization in the ITT Analysis Set | From first randomization up to 3.5 years, approximately | 
| Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life-Core 30(EORTC QLQC30) | 1) to assess overall health status/Quality of Life with 2 questions which are with range from minimum score 1 as worse outcome and maximum score 7 as higher values represent a better 2) to assess quality of life with 28 questions about Physical functioning, emotional functioning, social functioning etc. which are with range from minimum scores 1 representing as better to maximum scores 4 as worse outcome. | From first randomization up to 3.5 years, approximately | 
| Incidence and severity of treatment-emergent adverse events (AEs) | Incidence and severity of treatment-emergent adverse events (AEs) graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)v5.0 | From first randomization up to 3.5years, approximately | 
| Change from baseline in European Quality of Life 5-Dimension, 5-Level version (EQ-5D-5L) | to assess health status with 1) 5 questions about Mobility, Self-Care, Usual activities, Pain/Discomfort, Anxiety/Depression which are with 5 options. 2) one question about health status at the day of completing the questionnaire with range from minimum score 0 as worse outcome to maximum scores 100 as higher values represent as better. | From first randomization up to 3.5 years, approximately |