Study of Tislelizumab in Participants With Locally Advanced or Metastatic Urothelial Bladder Cancer

• ClinicalTrials.gov Identifier: NCT04004221
• Recruitment Status: Completed
• First Posted: July 1, 2019
• Results First Posted: March 16, 2023
• Last Update Posted: March 16, 2023
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Study Description

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

Condition or disease	Intervention/treatment	Phase
Locally Advanced or Metastatic Urothelial Bladder Cancer	Drug: Tislelizumab	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 113 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single-Arm, Multicenter Phase 2 Study of BGB-A317 in Patients With Previously Treated PD-L1+ Locally Advanced or Metastatic Urothelial Bladder Cancer
• Actual Study Start Date: June 16, 2017
• Actual Primary Completion Date: September 16, 2019
• Actual Study Completion Date: March 11, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Tislelizumab; 200mg intravenously (IV) every 3 weeks(Q3W)	Drug: Tislelizumab; 200mg intravenously (IV) every 3 weeks (Q3W); Other Name: BGB-A317

Outcome Measures

Primary Outcome Measures :

1. Objective Response Rate (ORR) as Assessed by Independent Review Committee (IRC) [ Time Frame: 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 :

1. Duration of Response (DOR) as Assessed by IRC [ Time Frame: 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
2. Progression-Free Survival (PFS) as Assessed by IRC [ Time Frame: 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
3. Disease Control Rate (DCR) as Assessed by IRC [ Time Frame: 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
4. Overall Survival (OS) [ Time Frame: 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
5. ORR as Assessed by the Investigators [ Time Frame: 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)
6. DOR as Assessed by Investigators Per RECIST Version 1.1 and irRECIST [ Time Frame: 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
7. PFS as Assessed by Investigators Per RECIST Version 1.1 and irRECIST [ Time Frame: 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
8. DCR as Assessed by Investigators Per RECIST Version 1.1 and irRECIST [ Time Frame: 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
9. Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

1. Participants with histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium
2. Disease progression during or following treatment with at least one platinum-containing regimen for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence
3. 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.
4. Participants must have at least one measurable lesion as defined per RECIST version 1.1 assessed by the investigator
5. Male or female, aged ≥18 years on day of signing informed consent
6. Participants have voluntarily agreed to participate by giving written informed consent
7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
8. Life expectancy ≥12 weeks

9. Participant must have adequate organ function as indicated by the following screening laboratory values obtained within 7 days prior to the first study treatment

   1. Absolute neutrophil count (ANC) ≥1.5×109/L
   2. Platelets ≥100×109/L
   3. Hemoglobin ≥9 g/dL or ≥5.6 mmol /L (Note: Criteria must be met without a transfusion within 14 days of obtaining the sample)
   4. Calculated creatinine clearance ≥ 30 milliliter (mL)/min (Cockcroft-Gault formula, see Appendix 5)
   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)
   6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 X ULN OR ≤ 5 X ULN for participants with liver metastases

10. Female participants are eligible to enter and participate in the study if they are of:

    1. 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)
    2. 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
11. 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 Exclusion Criteria:

1. History of severe hypersensitivity reactions to other humanized monoclonal antibodies
2. Prior active malignancy within 2 years prior to Cycle 1 Day 1.
3. Prior therapies targeting PD-1 or PD-L1.
4. Active brain or leptomeningeal metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments.
5. Participants with active autoimmune diseases or history of autoimmune diseases that may relapse should be excluded.
6. 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.
7. Has history of interstitial lung disease or non-infectious pneumonitis except for those induced by radiation therapies
8. 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.
9. With uncontrollable pleural effusion, pericardial effusion or ascites requiring pleurocentesis or abdominal tapping less than 4 weeks
10. 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
11. Known history of Human Immunodeficiency Virus (HIV)
12. 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
13. 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)
14. 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)
15. Prior allogeneic stem cell or solid organ transplant
16. Administration of a live or attenuated vaccine within 4 weeks prior to study drug administration
17. Major surgical procedure other than for diagnosis within 28 days prior to study drug administration

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

China, Anhui

Anhui Provincial Hospital

Hefei, Anhui, China, 230001

China, Beijing

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing, China, 100021

Peking University First Hospital

Beijing, Beijing, China, 100034

Peking University Third Hospital

Beijing, Beijing, China, 100191

Peking Union Medical College Hospital

Beijing, Beijing, China, 100730

China, Fujian

Fujian Medical University Union Hospital

Fuzhou, Fujian, China, 350001

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China, 361003

China, Guangdong

Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University

Guangzhou, Guangdong, China, 510120

China, Hubei

Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology

Wuhan, Hubei, China, 430030

China, Hunan

Xiangya Hospital central South University

Changsha, Hunan, China, 410008

Hunan Cancer Hospital

Changsha, Hunan, China, 410013

China, Jiangsu

Jiangsu Cancer Hospital

Nanjing, Jiangsu, China, 210000

China, Jiangxi

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China, 330006

Jiangxi Cancer Hospital

Nanchang, Jiangxi, China, 330029

China, Liaoning

The First Affiliated Hospital of Dalian Medical University

Dalian, Liaoning, China, 116027

The Second Hospital of Dalian Medical University

Dalian, Liaoning, China, 116027

The First Hospital of China Medical University

Shenyang, Liaoning, China, 110001

Liaoning Cancer Hospital

Shenyang, Liaoning, China, 110042

China, Shanghai

Fudan University Shanghai Cancer Center

Shanghai, Shanghai, China, 200032

Fudan University Zhongshan Hospital

Shanghai, Shanghai, China, 200032

Fudan University Hua Dong Hospital

Shanghai, Shanghai, China, 200040

China, Shanxi

The Second Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shanxi, China, 710004

China, Sichuan

West China Hospital, Sichuan University

Chengdu, Sichuan, China, 610041

China, Tianjin

The Second Hospital of Tianjin Medical University

Tianjin, Tianjin, China, 300211

China, Zhejiang

Zhejiang Provincial People's Hospital

Hangzhou, Zhejiang, China, 310014

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China, 310022

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China, 325000

Korea, Republic of

Samsung Medical Center

Seoul, Soul, Korea, Republic of, 100021

Seoul National University Hospital

Seoul, Korea, Republic of

Severance Hospital

Seoul, Korea, Republic of

Sponsors and Collaborators

BeiGene

Investigators

• Principal Investigator: Study Director; BeiGene

  Study Documents (Full-Text)

Documents provided by BeiGene:

Study Protocol  [PDF] August 5, 2020

Statistical Analysis Plan  [PDF] September 26, 2019

More Information

Publications of Results:

Ye D, Liu J, Zhou A, Zou Q, Li H, Fu C, Hu H, Huang J, Zhu S, Jin J, Ma L, Guo J, Xiao J, Park SH, Zhang D, Qiu X, Bao Y, Zhang L, Shen W, Bi F. Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma. Cancer Sci. 2021 Jan;112(1):305-313. doi: 10.1111/cas.14681. Epub 2020 Nov 6.

• Responsible Party: BeiGene
• ClinicalTrials.gov Identifier: NCT04004221
• Other Study ID Numbers: BGB-A317-204; CTR20170071 ( Registry Identifier: Center for drug evaluation, CDE )
• First Posted: July 1, 2019
• Results First Posted: March 16, 2023
• Last Update Posted: March 16, 2023
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Upon request, and subject to certain criteria, conditions, and exceptions, BeiGene will provide access to individual de-identified participant data from BeiGene-sponsored global interventional clinical studies conducted for medicines for indications that have been approved or in programmes that have been terminated. BeiGene will also consider requests for the protocol, data dictionary, and statistical analysis plan. Data requests can be submitted to medicalinformation@beigene.com.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Tislelizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents