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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Advanced or Metastatic Urothelial Carcinoma
• Intervention / Treatment: Biological: Toripalimab Injection; Drug: Gemcitabine Hydrochloride for Injection; Drug: Cisplatin for Injection / Carboplatin Injection; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 364
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jun Guo, Prof; Phone Number: 86-010-88196348; Email: guoj307@126.com

Study Locations

• China
  • Beijing, China
    • Peking University First Hospital
    • Contact: Zhisong He, Prof
  • Beijing, China
    • Peking University Cancer Hospital
    • Contact: Jun Guo, Prof
  • Shanghai, China
    • Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine
    • Contact: Yiran Huang, Prof

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Toripalimab Injection + chemotherapy group	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.; Drug: 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 Comparator: Placebo + chemotherapy group	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.; Drug: 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.; Drug: Placebo; Placebo iv infusion on Day 1 of each 3-week cycle. The cumulative duration of placebo is up to 2 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
IRC-PFS	Independent central radiological review committee-assessed progression-free survival as per RECIST1.1 criteria	Approximately 3 years
INV-ORR, IRC-ORR	Investigator- and IRC-assessed overall response rate	Approximately 3 years
INV-DCR, IRC-DCR	Investigator- and IRC-assessed disease control rate	Approximately 3 years
INV-DoR, IRC- DoR	Investigator- and IRC-assessed duration of response	Approximately 3 years
OS	Overall survival	Approximately 5 years
OS rate at 1 year	Overall survival rate at 1 year	Approximately 3 years
OS rate at 2 years	Overall survival rate at 2 years	Approximately 4 years
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
INV-PFS rate and IRC-PFS rate at 1 year	Investigator- and IRC-assessed progression-free survival rate at 1 year	Approximately 3 years
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed PFS	Investigator-assessed progression-free survival to explore the efficacy of crossover to Toripalimab Injection in control group	Approximately 4 years
Investigator-assessed ORR	Investigator-assessed overall response rate to explore the efficacy of crossover to Toripalimab Injection in control group	Approximately 4 years
Investigator-assessed DCR	Investigator-assessed disease control rate to explore the efficacy of crossover to Toripalimab Injection in control group	Approximately 4 years
Investigator-assessed DoR	Investigator-assessed duration of response to explore the efficacy of crossover to Toripalimab Injection in control group	Approximately 4 years

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): November 30, 2020
• Primary Completion (Anticipated): November 30, 2023
• Study Completion (Anticipated): November 30, 2025

Study Registration Dates

• First Submitted: September 17, 2020
• First Submitted That Met QC Criteria: September 23, 2020
• First Posted (Actual): September 29, 2020

Study Record Updates

• Last Update Posted (Actual): September 29, 2020
• Last Update Submitted That Met QC Criteria: September 23, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Carboplatin
• Other Study ID Numbers: JS001-038-III-UBC

Drug and device information, study documents

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