A Study Evaluating Toripalimab Injection Combined With Standard Chemotherapy as a First-line Treatment for Locally Advanced or Metastatic Urothelial Carcinoma

Locally Advanced or Metastatic Urothelial Carcinoma Clinical Trial

Official title:

A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center Clinical Study to Evaluate the Efficacy and Safety of Toripalimab Injection (JS001) in Combination With Standard Chemotherapy Versus Placebo in Combination With Standard Chemotherapy as the 1st-line Therapy for Treatment-naive Subjects With PD-L1-positive Locally Advanced or Metastatic Urothelial Carcinoma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04568304
• Other study ID #: JS001-038-III-UBC
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: November 30, 2020
• Est. completion date: November 30, 2025

Study information

• Verified date: September 2020
• Source: Shanghai Junshi Bioscience Co., Ltd.
• Contact: Jun Guo, Prof
• Phone: 86-010-88196348
• Email: guoj307[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is being conducted to evaluate the efficacy and safety of Toripalimab Injection in combination with chemotherapy compared to placebo in combination with chemotherapy in subjects with PD-L1-positive unresectable locally advanced or metastatic urothelial carcinoma who have received no previous systemic therapy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 364
• Est. completion date: November 30, 2025
• Est. primary completion date: November 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion criteria

1. Have full knowledge on this study and are willing to sign informed consent form (ICF);

2. Age 18-75 years at time of signing ICF, male or female;

3. The investigator judged that the subject is eligible for platinum-based chemotherapy;

4. Presence of histopathologically confirmed unresectable locally advanced (T4, any N; or any T, N2-3) or metastatic urothelial carcinoma;

5. No prior systemic anti-tumor therapy;

6. Subjects who are able to provide tumor tissue slides (= 5 slides) for PD-L1 test and the corresponding pathology report and whose PD-L1 test must be positive before randomization;

7. With at least one measurable lesion as per RECIST 1.1 criteria;

8. ECOG performance status score of 0-1;

9. Adequate function of vital organs.

Exclusion criteria

1. Have received anti-tumor treatments, including chemotherapy, radiotherapy or investigational product within 28 days before randomization;

2. Have received traditional Chinese medicines with anti-tumor activity or immunomodulators (eg. Interferon and Interleukin) within 14 days before randomization;

3. Previous use of anti-PD-1/PD-L1 agent or a drug acting on another co-inhibitory T cell receptor;

4. Subjects who are currently participating in or have participated in a study with investigational product within 4 weeks before administration;

5. Having received systemic corticosteroid therapy (dose equivalent to prednisone > 10 mg/day) within 14 days before randomization;

6. Subjects with active central nervous system (CNS) metastasis;

7. Grade 2 or higher peripheral neuropathy or hearing loss.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Locally Advanced or Metastatic Urothelial Carcinoma

Intervention

Biological:
• Toripalimab Injection
Toripalimab Injection 240 mg iv infusion on Day 1 of each 3-week cycle. The cumulative duration of Toripalimab Injection is up to 2 years.

Drug:
• Gemcitabine Hydrochloride for Injection
Gemcitabine 1000mg/? iv infusion, on Day 1 and Day 8 of each cycle, each treatment cycle is 3 weeks. The chemotherapy regimen will be administered for 6 cycles.
• Cisplatin for Injection / Carboplatin Injection
Cisplatin 70mg/? iv infusion, on Day 1 or Day 2 of each cycle, each treatment cycle is 3 weeks. Carboplatin AUC 4.5 iv infusion, on Day 1 or Day 2 of each cycle, each treatment cycle is 3 weeks. The chemotherapy regimen will be administered for 6 cycles.
• Placebo
Placebo iv infusion on Day 1 of each 3-week cycle. The cumulative duration of placebo is up to 2 years.

Locations

Country	Name	City	State
China	Peking University Cancer Hospital	Beijing
China	Peking University First Hospital	Beijing
China	Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Junshi Bioscience Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Investigator-assessed PFS	Investigator-assessed progression-free survival to explore the efficacy of crossover to Toripalimab Injection in control group	Approximately 4 years
Other	Investigator-assessed ORR	Investigator-assessed overall response rate to explore the efficacy of crossover to Toripalimab Injection in control group	Approximately 4 years
Other	Investigator-assessed DCR	Investigator-assessed disease control rate to explore the efficacy of crossover to Toripalimab Injection in control group	Approximately 4 years
Other	Investigator-assessed DoR	Investigator-assessed duration of response to explore the efficacy of crossover to Toripalimab Injection in control group	Approximately 4 years
Primary	Investigator-assessed progression-free survival (INV-PFS) as per RECIST 1.1 criteria	To evaluate the investigator-assessed progression-free survival following Toripalimab Injection in combination with chemotherapy compared to placebo in combination with chemotherapy in subjects with PD-L1-positive unresectable locally advanced or metastatic urothelial carcinoma who have received no previous systemic therapy	Approximately 3 years
Secondary	IRC-PFS	Independent central radiological review committee-assessed progression-free survival as per RECIST1.1 criteria	Approximately 3 years
Secondary	INV-ORR, IRC-ORR	Investigator- and IRC-assessed overall response rate	Approximately 3 years
Secondary	INV-DCR, IRC-DCR	Investigator- and IRC-assessed disease control rate	Approximately 3 years
Secondary	INV-DoR, IRC- DoR	Investigator- and IRC-assessed duration of response	Approximately 3 years
Secondary	OS	Overall survival	Approximately 5 years
Secondary	OS rate at 1 year	Overall survival rate at 1 year	Approximately 3 years
Secondary	OS rate at 2 years	Overall survival rate at 2 years	Approximately 4 years
Secondary	INV-PFS rate and IRC-PFS rate at 6 months	Investigator- and IRC-assessed progression-free survival rate at 6 months	Approximately 2.5 years
Secondary	INV-PFS rate and IRC-PFS rate at 1 year	Investigator- and IRC-assessed progression-free survival rate at 1 year	Approximately 3 years
Secondary	Incidence of AEs/SAEs	Study drug related adverse events, serious adverse events graded in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0	Approximately 4 years