Study of Tislelizumab in Participants With Locally Advanced or Metastatic Urothelial Bladder Cancer
- Conditions
- Locally Advanced or Metastatic Urothelial Bladder Cancer
- Interventions
- Registration Number
- NCT04004221
- Lead Sponsor
- BeiGene
- Brief Summary
This was a single-arm, multicenter, Phase 2 study to evaluate the efficacy and safety of the anti- programmed cell death-1(PD-1) monoclonal antibody BGB-A317 in participants with PD-L1+, locally advanced or metastatic Urothelial Bladder Cancer (UBC) who have progressed during or following a platinum-containing regimen
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 113
-
Participants with histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium
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Disease progression during or following treatment with at least one platinum-containing regimen for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence
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Participants must submit archival tumor tissue for determination of program death ligand-1 (PD-L1) expression and other biomarker analyses. PD-L1 expression will be assessed centrally, and participants who are tested as PD-L1 high are eligible.
-
Participants must have at least one measurable lesion as defined per RECIST version 1.1 assessed by the investigator
-
Male or female, aged ≥18 years on day of signing informed consent
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Participants have voluntarily agreed to participate by giving written informed consent
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Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
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Life expectancy ≥12 weeks
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Participant must have adequate organ function as indicated by the following screening laboratory values obtained within 7 days prior to the first study treatment
- Absolute neutrophil count (ANC) ≥1.5×109/L
- Platelets ≥100×109/L
- Hemoglobin ≥9 g/dL or ≥5.6 mmol /L (Note: Criteria must be met without a transfusion within 14 days of obtaining the sample)
- Calculated creatinine clearance ≥ 30 milliliter (mL)/min (Cockcroft-Gault formula, see Appendix 5)
- Serum total bilirubin ≤ 1.5 X upper limit of normal (ULN) (total bilirubin must be <4 X ULN for participants with Gilbert's syndrome)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 X ULN OR ≤ 5 X ULN for participants with liver metastases
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Female participants are eligible to enter and participate in the study if they are of:
- Non-childbearing potential (ie, physiologically incapable of becoming pregnant), including any female who i) Has had a hysterectomy ii) Has had a bilateral oophorectomy (ovariectomy) iii) Has had a bilateral tubal ligation iv) Is post menopausal (total cessation of menses for ≥1 year)
- Childbearing potential, has a negative serum pregnancy test at screening (within 7 days before the first investigational product administration), not be breast feeding, and agree to remain abstinent (refrain from heterosexual intercourse) or uses adequate contraceptive methods that result in a failure rate of <1% per year before study entry and throughout the study until 120 days after the last investigational product administration
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Male participants are eligible to participate in the study if they are vasectomized or agree to use contraception during the study treatment period and for at least 120 days after the last dose of study drug
Key
- History of severe hypersensitivity reactions to other humanized monoclonal antibodies
- Prior active malignancy within 2 years prior to Cycle 1 Day 1.
- Prior therapies targeting PD-1 or PD-L1.
- Active brain or leptomeningeal metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments.
- Participants with active autoimmune diseases or history of autoimmune diseases that may relapse should be excluded.
- Participants should be excluded if they have conditions requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration.
- Has history of interstitial lung disease or non-infectious pneumonitis except for those induced by radiation therapies
- With severe chronic or active infections (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal or antiviral therapy within 14 days prior to first dose of study drug.
- With uncontrollable pleural effusion, pericardial effusion or ascites requiring pleurocentesis or abdominal tapping less than 4 weeks
- Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina
- Known history of Human Immunodeficiency Virus (HIV)
- Participants with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carrier with HBV deoxyribonucleic acid (DNA) ≥500 IU/mL (or 2.5 × 103 cps/mL), or active hepatitis C should be excluded. Participant with inactive hepatitis B surface antigen (HBsAg) carrier, active HBV infection with sustained anti-HBV suppression (HBV DNA <500 IU/mL or 2.5 × 103 cps/mL) and participants whose hepatitis C has been cured (hepatitis C virus [HCV] ribonucleic acid [RNA] is lower than detection limit) can be enrolled
- Underlying medical conditions that, in the investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or adverse events (AEs)
- Prior chemotherapy, radiotherapy, immunotherapy or any investigational therapies (including Chinese herbal medicine and Chinese patent medicines) used to control cancer within 2 weeks of Cycle 1 Day 1. AEs associated with these therapies must be Grade 0-1, baseline or stabilized (except for alopecia)
- Prior allogeneic stem cell or solid organ transplant
- Administration of a live or attenuated vaccine within 4 weeks prior to study drug administration
- Major surgical procedure other than for diagnosis within 28 days prior to study drug administration
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Tislelizumab Tislelizumab 200mg intravenously (IV) every 3 weeks(Q3W)
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) as Assessed by Independent Review Committee (IRC) From the date of first dose up to approximately 2 years and 2 months ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) assessed by Independent Review Committee (IRC) using RECIST version 1.1
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) as Assessed by IRC From the date of first dose up to approximately 2 years and 2 months PFS is defined as the time from the date of first dose of study drug to the date of first documentation of disease progression assessed by IRC using RECIST version 1.1 or death, whichever occurs first
Disease Control Rate (DCR) as Assessed by IRC From the date of first dose up to approximately 2 years and 2 months DCR is defined as the percentage of participants who achieve CR, PR and stable disease (SD) assessed by IRC using RECIST version 1.1
Duration of Response (DOR) as Assessed by IRC From the date of first dose up to approximately 2 years and 2 months DOR - defined as the time from the first determination of a confirmed objective response by IRC according to RECIST version 1.1 until the first documentation of progression or death, whichever comes first
Overall Survival (OS) From the date of first dose up to approximately 2 years and 2 months OS - defined as the time from the date of first dose of study drug until the date of death from any cause
ORR as Assessed by the Investigators From the date of first dose up to approximately 2 years and 2 months ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) as assessed by the investigators per RECIST version 1.1 and immune related RECIST (irRECIST)
DOR as Assessed by Investigators Per RECIST Version 1.1 and irRECIST From the date of first dose up to approximately 2 years and 2 months DOR is defined as the time from the first determination of a confirmed objective response by the investigator according to RECIST version 1.1 and irRECIST until the first documentation of progression or death, whichever comes first
PFS as Assessed by Investigators Per RECIST Version 1.1 and irRECIST From the date of first dose up to approximately 2 years and 2 months PFS is defined as the time from the date of first dose of study drug to the date of first documentation of disease progression assessed by the investigator according to RECIST version 1.1 and irRECIST until the first documentation of progression or death, whichever comes first
DCR as Assessed by Investigators Per RECIST Version 1.1 and irRECIST From the date of first dose up to approximately 2 years and 2 months DCR is defined as the percentage of participants who achieve CR, PR and stable disease (SD) assessed by investigators per RECIST version 1.1 and irRECIST
Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) From the date of first dose until End of Study (approximately 3 years and 9 months) TEAE is defined as an adverse event (AE) that had an onset date or a worsening in severity from baseline pre-treatment) on or after the first dose of study drug up to 30 days following study drug .discontinuation. An SAE is any untoward medical occurrence that, at any dose that results in death or is life-threatening.
Trial Locations
- Locations (30)
Fudan University Hua Dong Hospital
🇨🇳Shanghai, Shanghai, China
Xiangya Hospital central South University
🇨🇳Changsha, Hunan, China
The First Affiliated Hospital of Dalian Medical University
🇨🇳Dalian, Liaoning, China
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Fudan University Zhongshan Hospital
🇨🇳Shanghai, Shanghai, China
Anhui Provincial Hospital
🇨🇳Hefei, Anhui, China
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
The First Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Cancer Hospital Chinese Academy of Medical Sciences
🇨🇳Beijing, Beijing, China
Peking University First Hospital
🇨🇳Beijing, Beijing, China
Jiangsu Cancer Hospital
🇨🇳Nanjing, Jiangsu, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
Samsung Medical Center
🇰🇷Seoul, Soul, Korea, Republic of
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China
Zhejiang Provincial People's Hospital
🇨🇳Hangzhou, Zhejiang, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Jiangxi Cancer Hospital
🇨🇳Nanchang, Jiangxi, China
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, Zhejiang, China
Peking University Third Hospital
🇨🇳Beijing, Beijing, China
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, Fujian, China
Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University
🇨🇳Guangzhou, Guangdong, China
The Second Hospital of Dalian Medical University
🇨🇳Dalian, Liaoning, China
Liaoning Cancer Hospital
🇨🇳Shenyang, Liaoning, China
The Second Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Xi'an, Shanxi, China
West China Hospital, Sichuan University
🇨🇳Chengdu, Sichuan, China
The Second Hospital of Tianjin Medical University
🇨🇳Tianjin, Tianjin, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China