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

NCT04004221 | Completed Phase 2 Results DMC

• 2 other identifiers: BGB-A317-204CTR20170071
• Study Type: interventional
• Target: 113
• Locations: 2 countries
• Sites: 27

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

Conditions

Locally Advanced or Metastatic Urothelial Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) as Assessed by Independent Review Committee (IRC)

  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

  From the date of first dose up to approximately 2 years and 2 months

Secondary Outcomes (9)

• Duration of Response (DOR) as Assessed by IRC

  From the date of first dose up to approximately 2 years and 2 months

• Progression-Free Survival (PFS) as Assessed by IRC

  From the date of first dose up to approximately 2 years and 2 months

• Disease Control Rate (DCR) as Assessed by IRC

  From the date of first dose up to approximately 2 years and 2 months

• Overall Survival (OS)

  From the date of first dose up to approximately 2 years and 2 months

• ORR as Assessed by the Investigators

  From the date of first dose up to approximately 2 years and 2 months

Study Arms (1)

Tislelizumab

EXPERIMENTAL

200mg intravenously (IV) every 3 weeks(Q3W)

Drug: Tislelizumab

Interventions

Tislelizumab DRUG

200mg intravenously (IV) every 3 weeks (Q3W)

Also known as: BGB-A317

Tislelizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium
• Disease progression during or following treatment with at least one platinum-containing regimen for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence
• 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
• Participants have voluntarily agreed to participate by giving written informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
• Life expectancy ≥12 weeks
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• BeiGene: lead

Study Sites (27)

Anhui Provincial Hospital

Hefei, Anhui, 230000, China

Location

Peking University Third Hospital

Beijing, Beijing Municipality, 100000, China

Location

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

Location

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

Location

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, 361003, China

Location

Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)

Guangzhou, Guangdong, 510000, China

Location

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

Wuhan, Hubei, 430030, China

Location

Xiangya Hospital of Central South University

Changsha, Hunan, 410008, China

Location

Jiangsu Province Cancer Hospital

Nanjing, Jiangsu, 210008, China

Location

The First Affiliated Hospital of Nanchang University Branch Donghu

Nanchang, Jiangxi, 330006, China

Location

Jiangxi Province Cancer Hospital

Nanchang, Jiangxi, 330029, China

Location

The Second Hospital of Dalian Medical University

Dalian, Liaoning, 116023, China

Location

The First Hospital of China Medical University

Shenyang, Liaoning, 110001, China

Location

Liaoning Cancer Hospital and Institute

Shenyang, Liaoning, 110042, China

Location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200000, China

Location

Affiliated Zhongshan Hospital of Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

Huadong Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, 200040, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

The Second Affiliated Hospital of Tianjin Medical University

Tianjin, Tianjin Municipality, 300000, China

Location

Zhejiang Provincial Peoples Hospital

Hangzhou, Zhejiang, 310014, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

The First Provincial Wenzhou Hospital of Zhejiang

Wenzhou, Zhejiang, 325000, China

Location

Seoul National University Hospital

Seoul, Seoul Teugbyeolsi, 03080, South Korea

Location

Gangnam Severance Hospital, Yonsei University Health System

Seoul, Seoul Teugbyeolsi, 06273, South Korea

Location

Samsung Medical Center

Seoul, Seoul Teugbyeolsi, 06351, South Korea

Location

Related Publications (2)

• 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.

  PMID: 33047430 RESULT

• Ye D, Desai J, Shi J, Liu SM, Shen W, Liu T, Shi Y, Wang D, Liang L, Yang S, Ma X, Jin W, Zhang P, Huang R, Shen Z, Zhang Y, Wu YL. Co-enrichment of CD8-positive T cells and macrophages is associated with clinical benefit of tislelizumab in solid tumors. Biomark Res. 2023 Mar 7;11(1):25. doi: 10.1186/s40364-023-00465-w.

  PMID: 36879284 DERIVED

MeSH Terms

Interventions

tislelizumab

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

+1-877-828-5568

Study Officials

• Study Director

  BeiGene

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2019
• First Posted: July 1, 2019
• Study Start: June 16, 2017
• Primary Completion: September 16, 2019
• Study Completion: March 11, 2021
• Last Updated: October 26, 2024
• Results First Posted: March 16, 2023

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

KR (3); CN (24)