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 Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Locally Advanced or Metastatic Urothelial Bladder Cancer
• Intervention: Drug: Tislelizumab
• Enrollment: 113

Participant Flow

Recruitment Details	113 participants were enrolled in 27 centers in China and 3 centers in South Korea. All efficacy evaluations were done until 16 September 2019, the primary data cut-off date. Safety evaluations were done until 11 March 2021, the study completion date.
Pre-assignment Details

Arm/Group Title	Tislelizumab
Arm/Group Description	Participants received 200mg tislelizumab intravenously (IV) every 3 weeks (Q3W) until disease progression or death
Period Title: Overall Study
Started	113
Completed	0
Not Completed	113
Reason Not Completed
Death	89
Withdrawal by Subject	5
Participants transferred to Long-Term Extension (LTE) study	9
Sponsor Decision	9
Participant refused to enter LTE	1

Baseline Characteristics

Arm/Group Title		Tislelizumab
Arm/Group Description		Participants received 200mg tislelizumab intravenously (IV) every 3 weeks (Q3W) until disease progression or death
Overall Number of Baseline Participants		113
Baseline Analysis Population Description		Safety Analysis Set includes all participants who received any dose of Tislelizumab
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	113 participants
		62.1 (7.85)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	113 participants
	Female	29 25.7%
	Male	84 74.3%
Race and Ethnicity Not Collected [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	0 participants
		[1] Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
South Korea	Number Analyzed	113 participants
		5
China	Number Analyzed	113 participants
		108

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR) as Assessed by Independent Review Committee (IRC)
Description	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
Time Frame	From the date of first dose up to approximately 2 years and 2 months

Outcome Measure Data

Analysis Population Description

The Efficacy Evaluable Analysis Set includes all participants who received any dose of tislelizumab and had measurable disease per IRC according to RECIST version 1.1 at baseline

Arm/Group Title	Tislelizumab
Arm/Group Description:	Participants received 200mg tislelizumab IV Q3W until disease progression or death
Overall Number of Participants Analyzed	104
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	24.0; (16.20 to 33.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tislelizumab
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	[Not Specified]
	Method	Exact Binomial Test
	Comments	1-sided p-value was based on binomial exact test of Tislelizumab versus historical rate of 0.1

2. Secondary Outcome

Title	Duration of Response (DOR) as Assessed by IRC
Description	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
Time Frame	From the date of first dose up to approximately 2 years and 2 months

Outcome Measure Data

Analysis Population Description

Efficacy Evaluable Analysis Set

Arm/Group Title	Tislelizumab
Arm/Group Description:	Participants received 200mg tislelizumab IV Q3W until disease progression or death
Overall Number of Participants Analyzed	104
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (8.41 to NA)

[1]

NA = Not Estimable due to insufficient number of events

3. Secondary Outcome

Title	Progression-Free Survival (PFS) as Assessed by IRC
Description	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
Time Frame	From the date of first dose up to approximately 2 years and 2 months

Outcome Measure Data

Analysis Population Description

Efficacy Evaluable Set

Arm/Group Title	Tislelizumab
Arm/Group Description:	Participants received 200mg tislelizumab IV Q3W until disease progression or death
Overall Number of Participants Analyzed	104
Median (95% Confidence Interval); Unit of Measure: Months
	2.1; (2.04 to 3.15)

4. Secondary Outcome

Title	Disease Control Rate (DCR) as Assessed by IRC
Description	DCR is defined as the percentage of participants who achieve CR, PR and stable disease (SD) assessed by IRC using RECIST version 1.1
Time Frame	From the date of first dose up to approximately 2 years and 2 months

Outcome Measure Data

Analysis Population Description

Efficacy Evaluable Set

Arm/Group Title	Tislelizumab
Arm/Group Description:	Participants received 200mg tislelizumab IV Q3W until disease progression or death
Overall Number of Participants Analyzed	104
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	38.5; (29.09 to 48.51)

5. Secondary Outcome

Title	Overall Survival (OS)
Description	OS - defined as the time from the date of first dose of study drug until the date of death from any cause
Time Frame	From the date of first dose up to approximately 2 years and 2 months

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	Tislelizumab
Arm/Group Description:	Participants received 200mg tislelizumab IV Q3W until disease progression or death
Overall Number of Participants Analyzed	113
Median (95% Confidence Interval); Unit of Measure: Months
	9.8; (7.46 to 12.48)

6. Secondary Outcome

Title	ORR as Assessed by the Investigators
Description	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)
Time Frame	From the date of first dose up to approximately 2 years and 2 months

Outcome Measure Data

Analysis Population Description

Efficacy Evaluable Analysis Set

Arm/Group Title	Tislelizumab
Arm/Group Description:	Participants received 200mg tislelizumab IV Q3W until disease progression or death
Overall Number of Participants Analyzed	104
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
RECIST	24.0; (16.20 to 33.41)
irRECIST	24.0; (16.20 to 33.41)

7. Secondary Outcome

Title	DOR as Assessed by Investigators Per RECIST Version 1.1 and irRECIST
Description	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
Time Frame	From the date of first dose up to approximately 2 years and 2 months

Outcome Measure Data

Analysis Population Description

Efficacy Evaluable Analysis Set

Arm/Group Title	Tislelizumab
Arm/Group Description:	Participants received 200mg tislelizumab IV Q3W until disease progression or death
Overall Number of Participants Analyzed	104
Median (95% Confidence Interval); Unit of Measure: Months
RECIST	NA [1]; (8.31 to NA)
irRECIST	NA [1]; (8.31 to NA)

[1]

NA = Not Estimable due to insufficient number of events

8. Secondary Outcome

Title	PFS as Assessed by Investigators Per RECIST Version 1.1 and irRECIST
Description	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
Time Frame	From the date of first dose up to approximately 2 years and 2 months

Outcome Measure Data

Analysis Population Description

Efficacy Evaluable Analysis Set

Arm/Group Title	Tislelizumab
Arm/Group Description:	Participants received 200mg tislelizumab IV Q3W until disease progression or death
Overall Number of Participants Analyzed	104
Median (95% Confidence Interval); Unit of Measure: Months
RECIST	2.1; (2.07 to 3.58)
irRECIST	2.6; (2.07 to 4.07)

9. Secondary Outcome

Title	DCR as Assessed by Investigators Per RECIST Version 1.1 and irRECIST
Description	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
Time Frame	From the date of first dose up to approximately 2 years and 2 months

Outcome Measure Data

Analysis Population Description

Efficacy Evaluable Analysis Set

Arm/Group Title	Tislelizumab
Arm/Group Description:	Participants received 200mg tislelizumab IV Q3W until disease progression or death
Overall Number of Participants Analyzed	104
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
RECIST	41.3; (31.77 to 51.42)
irRECIST	46.2; (36.33 to 56.20)

10. Secondary Outcome

Title	Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description	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.
Time Frame	From the date of first dose until End of Study (approximately 3 years and 9 months)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	Tislelizumab
Arm/Group Description:	Participants received 200mg tislelizumab IV Q3W until disease progression or death
Overall Number of Participants Analyzed	113
Measure Type: Number; Unit of Measure: Number of participants
Participants with At Least 1 TEAE	112
Grade 3 or Higher	64
Serious TEAEs	49

Adverse Events

Time Frame	From the date of first dose until end of study (approximately 3 years and 9 months)
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Tislelizumab
Arm/Group Description	Participants received 200mg tislelizumab intravenously Q3W until disease progression or death.
All-Cause Mortality
	Tislelizumab
	Affected / at Risk (%)
Total	89/113 (78.76%)
Serious Adverse Events
	Tislelizumab
	Affected / at Risk (%)	# Events
Total	49/113 (43.36%)
Blood and lymphatic system disorders
Agranulocytosis † 1	1/113 (0.88%)	1
Blood loss anaemia † 1	1/113 (0.88%)	1
Thrombocytopenia † 1	1/113 (0.88%)	1
Cardiac disorders
Cardiac failure † 1	1/113 (0.88%)	1
Ventricular fibrillation † 1	1/113 (0.88%)	1
Gastrointestinal disorders
Abdominal pain † 1	1/113 (0.88%)	1
Gastritis † 1	1/113 (0.88%)	1
Gastrointestinal haemorrhage † 1	1/113 (0.88%)	1
Ileus † 1	1/113 (0.88%)	1
Pancreatitis † 1	1/113 (0.88%)	1
Pancreatitis acute † 1	1/113 (0.88%)	1
General disorders
Death † 1	1/113 (0.88%)	1
General physical health deterioration † 1	3/113 (2.65%)	3
Multiple organ dysfunction syndrome † 1	1/113 (0.88%)	1
Oedema peripheral † 1	1/113 (0.88%)	1
Pyrexia † 1	4/113 (3.54%)	4
Hepatobiliary disorders
Bile duct stenosis † 1	1/113 (0.88%)	1
Hepatic failure † 1	3/113 (2.65%)	3
Liver injury † 1	1/113 (0.88%)	1
Infections and infestations
Abdominal infection † 1	1/113 (0.88%)	1
Febrile infection † 1	1/113 (0.88%)	1
Kidney infection † 1	1/113 (0.88%)	1
Pneumonia † 1	4/113 (3.54%)	4
Sepsis † 1	1/113 (0.88%)	1
Upper respiratory tract infection † 1	3/113 (2.65%)	3
Urinary tract infection † 1	3/113 (2.65%)	3
Injury, poisoning and procedural complications
Facial bones fracture † 1	1/113 (0.88%)	1
Optic nerve injury † 1	1/113 (0.88%)	1
Investigations
Alanine aminotransferase increased † 1	1/113 (0.88%)	1
Platelet count decreased † 1	1/113 (0.88%)	1
Metabolism and nutrition disorders
Decreased appetite † 1	2/113 (1.77%)	3
Hypercalcaemia † 1	2/113 (1.77%)	2
Hypokalaemia † 1	1/113 (0.88%)	1
Hyponatraemia † 1	1/113 (0.88%)	1
Hypoproteinaemia † 1	1/113 (0.88%)	1
Musculoskeletal and connective tissue disorders
Pathological fracture † 1	1/113 (0.88%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain † 1	2/113 (1.77%)	3
Malignant ascites † 1	1/113 (0.88%)	1
Nervous system disorders
Brain oedema † 1	1/113 (0.88%)	1
Dizziness † 1	1/113 (0.88%)	1
Paraplegia † 1	1/113 (0.88%)	1
Subarachnoid haemorrhage † 1	1/113 (0.88%)	1
Product Issues
Device occlusion † 1	1/113 (0.88%)	1
Renal and urinary disorders
Haematuria † 1	1/113 (0.88%)	1
Hydronephrosis † 1	1/113 (0.88%)	1
Renal failure † 1	2/113 (1.77%)	2
Renal impairment † 1	1/113 (0.88%)	1
Renal injury † 1	1/113 (0.88%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	1/113 (0.88%)	1
Immune-mediated pneumonitis † 1	1/113 (0.88%)	2
Respiratory arrest † 1	1/113 (0.88%)	1
Respiratory failure † 1	1/113 (0.88%)	1
Skin and subcutaneous tissue disorders
Dermatitis allergic † 1	1/113 (0.88%)	1
Drug eruption † 1	3/113 (2.65%)	3
Vascular disorders
Deep vein thrombosis † 1	2/113 (1.77%)	2
Shock haemorrhagic † 1	1/113 (0.88%)	1
1 Term from vocabulary, MedDRA 22.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Tislelizumab
	Affected / at Risk (%)	# Events
Total	110/113 (97.35%)
Blood and lymphatic system disorders
Anaemia † 1	44/113 (38.94%)	58
Endocrine disorders
Hyperthyroidism † 1	6/113 (5.31%)	7
Hypothyroidism † 1	11/113 (9.73%)	19
Gastrointestinal disorders
Abdominal distension † 1	12/113 (10.62%)	15
Abdominal pain † 1	9/113 (7.96%)	9
Constipation † 1	25/113 (22.12%)	28
Diarrhoea † 1	10/113 (8.85%)	10
Nausea † 1	13/113 (11.50%)	16
Vomiting † 1	10/113 (8.85%)	11
General disorders
Asthenia † 1	9/113 (7.96%)	12
Fatigue † 1	10/113 (8.85%)	10
Oedema peripheral † 1	8/113 (7.08%)	8
Pyrexia † 1	22/113 (19.47%)	27
Infections and infestations
Nasopharyngitis † 1	10/113 (8.85%)	14
Upper respiratory tract infection † 1	11/113 (9.73%)	12
Urinary tract infection † 1	23/113 (20.35%)	33
Investigations
Alanine aminotransferase increased † 1	19/113 (16.81%)	25
Aspartate aminotransferase increased † 1	22/113 (19.47%)	28
Blood alkaline phosphatase increased † 1	15/113 (13.27%)	19
Blood bilirubin increased † 1	8/113 (7.08%)	13
Blood creatine phosphokinase MB increased † 1	7/113 (6.19%)	10
Blood creatinine increased † 1	19/113 (16.81%)	21
Blood lactate dehydrogenase increased † 1	10/113 (8.85%)	11
Blood urea increased † 1	9/113 (7.96%)	12
Gamma-glutamyltransferase increased † 1	8/113 (7.08%)	8
Neutrophil count decreased † 1	6/113 (5.31%)	18
Platelet count decreased † 1	6/113 (5.31%)	7
Weight decreased † 1	7/113 (6.19%)	7
White blood cell count decreased † 1	8/113 (7.08%)	15
Metabolism and nutrition disorders
Decreased appetite † 1	23/113 (20.35%)	27
Hyperglycaemia † 1	7/113 (6.19%)	8
Hyperkalaemia † 1	7/113 (6.19%)	9
Hypertriglyceridaemia † 1	6/113 (5.31%)	16
Hyperuricaemia † 1	7/113 (6.19%)	12
Hypoalbuminaemia † 1	20/113 (17.70%)	24
Hypokalaemia † 1	6/113 (5.31%)	6
Hyponatraemia † 1	21/113 (18.58%)	25
Musculoskeletal and connective tissue disorders
Back pain † 1	12/113 (10.62%)	16
Nervous system disorders
Dizziness † 1	6/113 (5.31%)	7
Psychiatric disorders
Insomnia † 1	6/113 (5.31%)	7
Renal and urinary disorders
Haematuria † 1	8/113 (7.08%)	9
Proteinuria † 1	9/113 (7.96%)	11
Respiratory, thoracic and mediastinal disorders
Cough † 1	9/113 (7.96%)	9
Skin and subcutaneous tissue disorders
Pruritus † 1	23/113 (20.35%)	34
Rash † 1	17/113 (15.04%)	27
1 Term from vocabulary, MedDRA 22.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information & may request a further delay to protect its IP rights

Results Point of Contact

• Name/Title: Study Director
• Organization: BeiGene
• Phone: +1-877-828-5568
• EMail: clinicaltrials@beigene.com

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 Submitted: June 28, 2019
• First Posted: July 1, 2019
• Results First Submitted: March 1, 2022
• Results First Posted: March 16, 2023
• Last Update Posted: March 16, 2023