9MW2821 Combined With Toripalimab Injection in Subjects With Local Advanced or Metastatic Urothelial Cancer

Study Overview
=================
Brief Summary
-----------------
This is a phase Ib/II, open-label, multicenter clinical study to evaluate the safety, tolerability, efficacy, pharmacokinetics and immunogenicity of 9MW2821 combined with Toripalimab injection in subjects with local advanced or metastatic urothelial cancer.

Official Title
-----------------
A Phase Ib/II, Open-label, Single Arm, Multicenter Clinical Study to Evaluate the Safety and Efficacy of 9MW2821 Combined With Toripalimab Injection in Subjects With Local Advanced or Metastatic Urothelial Cancer

Conditions
-----------------
Advanced Urothelial Carcinoma

Intervention / Treatment
-----------------
* Drug: 9MW2821
* Drug: Toripalimab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Sign and date the informed consent form e approved by independent ethics committe. Male or female subjects aged 18 to 80 years (including 18 and 80 years). ECOG status of 0 or 1. Histologically or cytologically confirmed local advanced or metastatic urothelial cancer Subjects have received at least 1 line advanced standard therapy or were not treated before Subjects must submit tumor tissues for test Life expectancy of ≥ 12 weeks. Subjects must have measurable lesions according to RECIST (version 1.1). Adequate organ functions Sexually active fertile subjects, and their partners, must agree to use methods of contraception during the study and at least 6 months after termination of study therapy. Subjects are willing to follow study procedures. Exclusion Criteria: Anti-tumor treatment such as chemotherapy and radiotherapy within 21 days prior to the first dose of study drug. Major surgery within 28 days prior to first dose of study drug. PD-1/PD-L1/PD-L2 inhibitors used in the previous treatment for La/m UC. Previous treatment with ADCs conjugated with MMAE payload. Clinical significantly toxicity Grade ≥ 2 (except alopecia and pigmentation) related to previous treatment. Peripheral neuropathy Grade ≥ 2. Poorly controlled blood sugar. Increased risks of corneal disease assessed by the investigator prior to the first dose of study drug. Documented history of clinically significant cardiac or cerebrovascular diseases within 6 months prior to the first dose of study drug. Active infections, such as uncontrolled HBV/HCV/HIV/TB infection, etc. Other serious or uncontrolled diseases, such as serious interstitial pneumonia/asthma, serious thromboembolic events, etc. Poorly controlled central nervous system metastases. Organ transplantation or allogeneic hematopoietic stem cell transplantation in the past. History of drug abuse or mental illness. Known allergic sensitivity to any of the ingredients of the study drug. Any P-glycoprotein (P-gp) inducers/inhibitors or potent CYP3A4 inducers/inhibitors within 14 days prior to the first dose of study drug. History of autoimmune disease requiring systemic treatment within 2 years before the first dose. Any live vaccines within 4 weeks before first dose of study drug or during the study. Use of any investigational drug or medical instruments within 28 days prior to the first dose of study drug. History of another malignancy within 3 years before the first dose of study drug. Subjects with curable malignancies are allowed. Other conditions unsuitable into the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 9MW2821+Toripalimab<br> | Drug: 9MW2821<br>* 1.0/1.25/1.5 mg/kg, intravenous (IV) infusion every cycle until disease progression or intolerable toxicity, etc.<br>* Other names: 9MW2821 injection;Drug: Toripalimab<br>* 240mg intravenous (IV) infusion every cycle until disease progression or intolerable toxicity, etc.<br>* Other names: Toripalimab injection;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of AE/SAE | adverse event(AE) 、serious adverse event(SAE) | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate, ORR | complete response (CR) or partial response (PR) | Up to 24 months | 
| Duration of Response, DOR | Time from the date of the first CR or PR to the earliest date of disease progression or death | Up to 24 months | 
| Time To Response, TTR | Time from the date of first infusion to the date of CR or PR | Up to 24 months | 
| Disease Control Rate, DCR | the percentage of subjects who experience CR, PR or stable disease (SD) | Up to 24 months | 
| Progression-Free Survival, PFS | Time from the date of first infusion to the earliest date of disease progression or death | Up to 24 months | 
| Overall Survival, OS | Time from the date of first infusion to the date of death | Up to 24 months | 
| Pharmacokinetics parameter | drug concentration of 9MW2821 | Up to 12 months | 
| Immunogenicity parameter | Anti-Drug Antibody (ADA) of 9MW2821 | Up to 12 months |