Clinical trial NCT04004221: Study of Tislelizumab in Participants With Locally Advanced or Metastatic Urothelial Bladder Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Locally Advanced or Metastatic Urothelial Bladder Cancer
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2019-07-01
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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.

Primary outcomes:
measure: Objective Response Rate (ORR) as Assessed by Independent Review Committee (IRC)
timeFrame: From the date of first dose up to approximately 2 years and 2 months
Secondary outcomes:
measure: Duration of Response (DOR) as Assessed by IRC
timeFrame: From the date of first dose up to approximately 2 years and 2 months
measure: Progression-Free Survival (PFS) as Assessed by IRC
timeFrame: From the date of first dose up to approximately 2 years and 2 months
measure: Disease Control Rate (DCR) as Assessed by IRC
timeFrame: From the date of first dose up to approximately 2 years and 2 months
measure: Overall Survival (OS)
timeFrame: From the date of first dose up to approximately 2 years and 2 months
measure: ORR as Assessed by the Investigators
timeFrame: From the date of first dose up to approximately 2 years and 2 months
measure: DOR as Assessed by Investigators Per RECIST Version 1.1 and irRECIST
timeFrame: From the date of first dose up to approximately 2 years and 2 months
measure: PFS as Assessed by Investigators Per RECIST Version 1.1 and irRECIST
timeFrame: From the date of first dose up to approximately 2 years and 2 months
measure: DCR as Assessed by Investigators Per RECIST Version 1.1 and irRECIST
timeFrame: From the date of first dose up to approximately 2 years and 2 months
measure: Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From the date of first dose until End of Study (approximately 3 years and 9 months)
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)
state: Guangdong
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Cancer Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University Branch Donghu
state: Jiangxi
city: Nanchang
country: China
facility: Jiangxi Province Cancer Hospital
state: Jiangxi
city: Dalian
country: China
facility: The Second Hospital of Dalian Medical University
state: Liaoning
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: Liaoning Cancer Hospital and Institute
state: Liaoning
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Affiliated Zhongshan Hospital of Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Huadong Hospital Affiliated to Fudan University
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: The Second Affiliated Hospital of Tianjin Medical University
state: Tianjin
city: Hangzhou
country: China
facility: Zhejiang Provincial Peoples Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First Provincial Wenzhou Hospital of Zhejiang
state: Zhejiang
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital, Yonsei University Health System
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
Study officials:
affiliation: BeiGene
name: Study Director
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.