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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Urothelial Carcinoma
• Intervention / Treatment: Drug: Tislelizumab; Drug: Cisplatin; Drug: Gemcitabine Hydrochloride; Drug: Carboplatin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 420
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: BeiGene; Phone Number: +1-877-828-5568; Email: clinicaltrials@beigene.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100034
      • Recruiting
      • Peking University First Hospital
    • Beijing, Beijing, China, 100050
      • Recruiting
      • Beijing Friendship Hospital, Capital Medical University
  • Chongqing
    • Chongqing, Chongqing, China, 400030
      • Recruiting
      • Chongqing Cancer Hospital
  • Fujian
    • Quanzhou, Fujian, China, 362001
      • Recruiting
      • The Second Affiliated Hospital of Fujian Medical University
    • Xiamen, Fujian, China, 361003
      • Recruiting
      • The First Affiliated Hospital of Xiamen University
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Zhujiang Hospital of Southern Medical University
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Recruiting
      • Nanjing Drum Tower Hospital,The Affiliated Hospital of Nanjing University Medical School
  • Jilin
    • Changchun, Jilin, China, 130021
      • Recruiting
      • The First Hospital of Jilin University
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Fudan University Shanghai Cancer Center
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital, Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300000
      • Recruiting
      • The Second Affiliated Hospital of Tianjin Medical University
  • Xinjiang
    • Urumqi, Xinjiang, China, 830000
      • Recruiting
      • Affiliated Cancer Hospital of Xinjiang Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310014
      • Recruiting
      • Zhejiang Provincial Peoples Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tislelizumab in combination with chemotherapy; Tislelizumab: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles	Drug: Tislelizumab; 200 mg administered Intravenously (IV) as specified in the treatment arm; Other Names: BGB-A317; Drug: Cisplatin; 70 mg/m2 administered IV as specified in the treatment arm; Drug: Gemcitabine Hydrochloride; 1000 mg/m2 administered IV as specified in the treatment arm; Drug: Carboplatin; Area Under the Curve (AUC) 4.5 administered IV as specified in the treatment arm
Placebo Comparator: Placebo in combination with chemotherapy; Placebo: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles	Drug: Cisplatin; 70 mg/m2 administered IV as specified in the treatment arm; Drug: Gemcitabine Hydrochloride; 1000 mg/m2 administered IV as specified in the treatment arm; Drug: Carboplatin; Area Under the Curve (AUC) 4.5 administered IV as specified in the treatment arm; Drug: Placebo; Tislelizumab placebo to match

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS) in the Intent to Treat (ITT) set	From first randomization up to 3.5 years, approximately

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Principal Investigator: Dingwei Ye, MD, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2019
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): January 1, 2024

Study Registration Dates

• First Submitted: May 23, 2019
• First Submitted That Met QC Criteria: May 27, 2019
• First Posted (Actual): May 30, 2019

Study Record Updates

• Last Update Posted (Actual): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Carboplatin; Gemcitabine; Tislelizumab
• Other Study ID Numbers: BGB-A317-310; CTR20190543 (Registry Identifier: Center for drug evaluation, CFDA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No