Urothelial Carcinoma
Conditions
Brief summary
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.
Interventions
DRUGTislelizumab
200 mg administered Intravenously (IV) as specified in the treatment arm
DRUGPlacebo
Tislelizumab placebo to match
DRUGCisplatin
70 mg/m2 administered IV as specified in the treatment arm
DRUGGemcitabine Hydrochloride
1000 mg/m2 administered IV as specified in the treatment arm
DRUGCarboplatin
Area Under the Curve (AUC) 4.5 administered IV as specified in the treatment arm
Sponsors
BeiGene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Male or female aged 18 to 75 years on the day of signing the Informed Consent Form (ICF) 2. Histologically confirmed, inoperable, locally advanced, or metastatic urothelial cancer (UC) 3. Must be eligible to receive cisplatin or carboplatin in the investigator's judgment 4. Have had no prior systemic chemotherapy for locally advanced or metastatic UC 5. Must be able to provide fresh or archival tumor tissues with an associated pathological report. 6. Must have evaluable disease (either measurable or non-measurable) as defined per RECIST v1.1. 7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1. 8. Adequate organ function before randomization: Key
Exclusion criteria
1. 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. 2. Any approved anticancer therapy within 28 days before randomization. 3. Active leptomeningeal disease or uncontrolled, untreated brain metastasis 4. Participants with uncontrolled hypercalcemia 5. Participants with active autoimmune diseases or history of autoimmune diseases that may relapse 6. History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled diseases 7. A known history of HIV infection. 8. Prior allogeneic stem cell transplantation or organ transplantation. 9. 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survival (OS) in the Intent to Treat (ITT) set | From first randomization up to 3.5 years, approximately |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) per RECIST v1.1 in ITT | From first randomization up to 3.5 years, approximately | 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 |
| Duration of response (DOR) | From first randomization up to 3.5 years, approximately | 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 |
| Progression-free survival (PFS) | From first randomization up to 3.5 years, approximately | 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 |
| Overall survival rate at 1 and 2 years for each treatment arm | From first randomization up to 3.5 years, approximately | the proportion of OS participants at 1 year and 2 years from randomization in the ITT Analysis Set |
| Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life-Core 30(EORTC QLQC30) | From first randomization up to 3.5 years, approximately | 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. |
| Incidence and severity of treatment-emergent adverse events (AEs) | From first randomization up to 3.5years, approximately | 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 |
| Change from baseline in European Quality of Life 5-Dimension, 5-Level version (EQ-5D-5L) | From first randomization up to 3.5 years, approximately | 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. |
Countries
China, Taiwan
Contacts
PRINCIPAL_INVESTIGATORDingwei Ye, MD
Fudan University
Outcome results
None listed