Locally Advanced or Metastatic Urothelial Carcinoma
Conditions
Brief 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.
Interventions
BIOLOGICALToripalimab 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.
DRUGGemcitabine 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.
DRUGCisplatin 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.
DRUGPlacebo
Placebo iv infusion on Day 1 of each 3-week cycle. The cumulative duration of placebo is up to 2 years.
Sponsors
Shanghai Junshi Bioscience Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Investigator-assessed progression-free survival (INV-PFS) as per RECIST 1.1 criteria | Approximately 3 years | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| IRC-PFS | Approximately 3 years | Independent central radiological review committee-assessed progression-free survival as per RECIST1.1 criteria |
| INV-ORR, IRC-ORR | Approximately 3 years | Investigator- and IRC-assessed overall response rate |
| INV-DCR, IRC-DCR | Approximately 3 years | Investigator- and IRC-assessed disease control rate |
| INV-DoR, IRC- DoR | Approximately 3 years | Investigator- and IRC-assessed duration of response |
| OS | Approximately 5 years | Overall survival |
| OS rate at 1 year | Approximately 3 years | Overall survival rate at 1 year |
| OS rate at 2 years | Approximately 4 years | Overall survival rate at 2 years |
| INV-PFS rate and IRC-PFS rate at 6 months | Approximately 2.5 years | Investigator- and IRC-assessed progression-free survival rate at 6 months |
| INV-PFS rate and IRC-PFS rate at 1 year | Approximately 3 years | Investigator- and IRC-assessed progression-free survival rate at 1 year |
| Incidence of AEs/SAEs | Approximately 4 years | 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 |
Countries
China
Outcome results
None listed