Study of Tislelizumab in Combination With Chemotherapy Compared to Chemotherapy Alone for Participants With Urothelial Carcinoma

Urothelial Carcinoma Clinical Trial

Official title:

A Phase 3, Multi-center, Randomized, Double-Blind, Placebo-Controlled Study of Either Cisplatin or Carboplatin +Gemcitabine + Tislelizumab Compared With Either Cisplatin or Carboplatin + Gemcitabine + Placebo as First-line Treatment for Patients With Locally Advanced or Metastatic Urothelial Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03967977
• Other study ID #: BGB-A317-310
• Secondary ID: CTR20190543
• Status: Recruiting
• Phase: Phase 3
• Start date: May 29, 2019
• Est. completion date: June 2027

Study information

• Verified date: June 2024
• Source: BeiGene
• Contact: BeiGene
• Phone: +1-877-828-5568
• Email: clinicaltrials[@]beigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, randomized, double-blind, placebo-controlled, Phase 3 study designed to compare the efficacy and safety of tislelizumab + either cisplatin or carboplatin + gemcitabine versus placebo+ either cisplatin or carboplatin + gemcitabine in approximately 420 participants with locally advanced or metastatic urothelial carcinoma who have not received prior systemic therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 420
• Est. completion date: June 2027
• Est. primary completion date: June 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key Inclusion Criteria:

1. Male or female aged 18 to 75 years on the day of signing the Informed Consent Form (ICF)

2. Histologically confirmed, inoperable, locally advanced, or metastatic urothelial cancer (UC)

3. Must be eligible to receive cisplatin or carboplatin in the investigator's judgment

4. Have had no prior systemic chemotherapy for locally advanced or metastatic UC

5. Must be able to provide fresh or archival tumor tissues with an associated pathological report.

6. Must have evaluable disease (either measurable or non-measurable) as defined per RECIST v1.1.

7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.

8. Adequate organ function before randomization:

Key Exclusion Criteria:

1. Received prior therapies targeting PD-1, PD-L1, PD-L2, CTLA4, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.

2. Any approved anticancer therapy within 28 days before randomization.

3. Active leptomeningeal disease or uncontrolled, untreated brain metastasis

4. Participants with uncontrolled hypercalcemia

5. Participants with active autoimmune diseases or history of autoimmune diseases that may relapse

6. History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled diseases

7. A known history of HIV infection.

8. Prior allogeneic stem cell transplantation or organ transplantation.

9. History of severe hypersensitivity reactions to other monoclonal antibodies. 10.History of allergic reactions to cisplatin, carboplatin, or other platinum-containing compounds.

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Urothelial Carcinoma

Intervention

Drug:
• Tislelizumab
200 mg administered Intravenously (IV) as specified in the treatment arm
• Placebo
Tislelizumab placebo to match
• Cisplatin
70 mg/m2 administered IV as specified in the treatment arm
• Gemcitabine Hydrochloride
1000 mg/m2 administered IV as specified in the treatment arm
• Carboplatin
Area Under the Curve (AUC) 4.5 administered IV as specified in the treatment arm

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	The First Hospital of Jilin University	Changchun	Jilin
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	Chongqing Cancer Hospital	Chongqing	Chongqing
China	Zhujiang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Zhejiang Provincial Peoples Hospital	Hangzhou	Zhejiang
China	Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School	Nanjing	Jiangsu
China	The Second Affiliated Hospital of Fujian Medical University	Quanzhou	Fujian
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	The Second Affiliated Hospital of Tianjin Medical University	Tianjin	Tianjin
China	Affiliated Cancer Hospital of Xinjiang Medical University	Urumqi	Xinjiang
China	Union Hospital of Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS) in the Intent to Treat (ITT) set		From first randomization up to 3.5 years, approximately
Secondary	Overall response rate (ORR) per RECIST v1.1 in ITT	the proportion of participants who had Complete Response (CR) or Partial Response (PR) as assessed by the investigator per RECIST v1.1 in the ITT Analysis Set	From first randomization up to 3.5 years, approximately
Secondary	Duration of response (DOR)	the time from the first occurrence of a documented objective response to documented Progressive Disease (PD), or death from any cause, whichever occurs first, as determined by the investigator per RECIST v1.1 in the ITT Analysis Set	From first randomization up to 3.5 years, approximately
Secondary	Progression-free survival (PFS)	the time from randomization to the first objectively documented PD, or death from any cause, whichever occurs first, as determined by the investigator per RECIST v1.1 in the ITT Analysis Set	From first randomization up to 3.5 years, approximately
Secondary	Overall survival rate at 1 and 2 years for each treatment arm	the proportion of OS participants at 1 year and 2 years from randomization in the ITT Analysis Set	From first randomization up to 3.5 years, approximately
Secondary	Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life-Core 30(EORTC QLQC30)	1) to assess overall health status/Quality of Life with 2 questions which are with range from minimum score 1 as worse outcome and maximum score 7 as higher values represent a better 2) to assess quality of life with 28 questions about Physical functioning, emotional functioning, social functioning etc. which are with range from minimum scores 1 representing as better to maximum scores 4 as worse outcome.	From first randomization up to 3.5 years, approximately
Secondary	Incidence and severity of treatment-emergent adverse events (AEs)	Incidence and severity of treatment-emergent adverse events (AEs) graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)v5.0	From first randomization up to 3.5years, approximately
Secondary	Change from baseline in European Quality of Life 5-Dimension, 5-Level version (EQ-5D-5L)	to assess health status with 1) 5 questions about Mobility, Self-Care, Usual activities, Pain/Discomfort, Anxiety/Depression which are with 5 options. 2) one question about health status at the day of completing the questionnaire with range from minimum score 0 as worse outcome to maximum scores 100 as higher values represent as better.	From first randomization up to 3.5 years, approximately