Back to resultsA Study of RC48-ADC Combined With Toripalimab For First-line Treatment of Urothelial Carcinoma
Primary Purpose
Urothelial Carcinoma, HER2-expressing
Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
RC48-ADC
Toripalimab
Gemcitabine
Cisplatin
Carboplatin
Sponsored by
About this trial
This is an interventional treatment trial for Urothelial Carcinoma focused on measuring Urothelial Carcinoma, HER2-expressing, RC48, First-Line
Eligibility Criteria
Inclusion Criteria:
- Expected survival ≥12 weeks.
- Locally advanced unresectable or metastatic UC with histopathological confirmation, including UC originating from the renal pelvis, ureters, bladder, or urethra.
- Participants must not have received prior systemic therapy for locally advanced or metastatic urothelial carcinoma with the following exceptions:
Participants that received neoadjuvant chemotherapy with recurrence >6 months from completion of therapy are permitted; Participants that received adjuvant chemotherapy following cystectomy with recurrence >6 months from completion of therapy are permitted.
- At least one measurable lesion based on RECIST version 1.1
- HER2-expressing status determined by the central laboratory to be IHC 1+, 2+ or 3+.
- ECOG performance status score: 0 or 1.
- Adequate cardiac, bone marrow, hepatic, renal, and coagulation functions.
Exclusion Criteria:
- Known hypersensitivity to RC48-ADC or Toripalimab or any of its components.
- History of major surgery within 4 weeks of planned start of trial treatment.
- Toxicity from a previous treatment has not returned to Grade 0-1.
- Prior ADCs or PD-1/PD-L1 inhibitor therapy.
- Active central nervous system (CNS) metastases.
- Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection.
- History of other malignancy within the previous 5 years, except for low-risk localized prostate cancer, appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or cancers with a similar curative outcome as those mentioned above.
- Other serious, uncontrolled concomitant diseases that may affect protocol compliance or interpretation of outcomes, including active opportunistic infections or advanced (severe) infections, or uncontrolled diabetes.
- Active autoimmune diseases that require systemic therapy over the past 2 years. Replacement therapies (such as thyroxine, insulin, or physiological replacement of glucocorticoids due to renal or pituitary deficiency) are allowed.
- Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
Sites / Locations
- Cancer Hospital Chinese Academy of Medical SciencesRecruiting
- Beijing Cancer HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
RC48-ADC + JS001
Gemcitabine + cisplatin/carboplatin
Arm Description
Participants will receive RC48-ADC + JS001 every 2 weeks (Q2W) until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
Participants will receive Gemcitabine + cisplatin or carboplatin every 3 weeks (Q3W) for maximum 6 weeks or until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
Outcomes
Primary Outcome Measures
Progression-free survival (PFS), evaluated by independent review committee
Progression-free survival (PFS) refers to the time from the date of randomization to the first researcher's evaluation of disease progression or death (calculated by the event that occurred first). The disease progression will be evaluated by independent review committee according to the RECIST 1.1 standard.
Overall survival (OS)
Overall survival (OS) refers to the time from the date of randomization to the date of death of the subject.
Secondary Outcome Measures
Objective remission rate (ORR)
The objective response rate will be mainly analyzed by the independent efficacy evaluation committee according to the RECIST 1.1 standard tumor evaluation (the evaluation by the investigator will also be performed).
Progression-free survival (PFS), evaluated by the investigator
Progression-free survival (PFS) refers to the time from the date of randomization to the first researcher's evaluation of disease progression or death (calculated by the event that occurred first). The disease progression will be evaluated by the researchers according to the RECIST 1.1 standard.
Duration of relief (DOR)
DOR is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death
Disease control rate (DCR)
Disease control rate (DCR) is defined as cases where objective remission (assessed as complete remission or partial remission according to RECIST 1.1 standard) or stable disease during the study.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05302284
Brief Title
A Study of RC48-ADC Combined With Toripalimab For First-line Treatment of Urothelial Carcinoma
Official Title
A Open-Label, Multicenter, Randomised, Controlled Phase 3 Study of RC48-ADC Plus Toripalimab Versus Chemotherapy Alone in Previously Untreated Unresectable Locally Advanced or Metastatic Urothelial Carcinoma With HER2-Expressing
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 14, 2022 (Actual)
Primary Completion Date
December 31, 2026 (Anticipated)
Study Completion Date
April 30, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
RemeGen Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a Phase 3, Open-Label, Multicenter, Randomised, Controlled Study designed to compare RC48-ADC in Combination With JS001 to Chemotherapy Alone in Previously Untreated HER2-Expressing Unresectable Locally Advanced or Metastatic Urothelial Carcinoma.
Detailed Description
This is a Phase 3, Open-Label, Multicenter, Randomised, Controlled Study to evaluate the efficacy and safety of RC48-ADC,a recombinant humanized anti-HER2 monoclonal antibody-Monomethyl auristatin E (MMAE) conjugate, in Combination With JS001,a PD-1 monoclonal antibody, for the treatment of Previously Untreated HER2-Expressing Unresectable Locally Advanced or Metastatic Urothelial Carcinoma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urothelial Carcinoma, HER2-expressing
Keywords
Urothelial Carcinoma, HER2-expressing, RC48, First-Line
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
452 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
RC48-ADC + JS001
Arm Type
Experimental
Arm Description
Participants will receive RC48-ADC + JS001 every 2 weeks (Q2W) until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
Arm Title
Gemcitabine + cisplatin/carboplatin
Arm Type
Active Comparator
Arm Description
Participants will receive Gemcitabine + cisplatin or carboplatin every 3 weeks (Q3W) for maximum 6 weeks or until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
Intervention Type
Drug
Intervention Name(s)
RC48-ADC
Other Intervention Name(s)
Disitamab Vedotin
Intervention Description
2.0 mg/kg IV every 2 weeks
Intervention Type
Drug
Intervention Name(s)
Toripalimab
Other Intervention Name(s)
JS001
Intervention Description
3.0 mg/kg IV every 2 weeks
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
1000mg/m2 IV infusion on Days 1 and 8 of every 3 week cycle
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
70mg/m2 IV infusion on Day 1 of every 3 week cycle
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
AUC=4.5, IV infusion on Day 1 of every 3 week cycle
Primary Outcome Measure Information:
Title
Progression-free survival (PFS), evaluated by independent review committee
Description
Progression-free survival (PFS) refers to the time from the date of randomization to the first researcher's evaluation of disease progression or death (calculated by the event that occurred first). The disease progression will be evaluated by independent review committee according to the RECIST 1.1 standard.
Time Frame
Up to approximately 3 years
Title
Overall survival (OS)
Description
Overall survival (OS) refers to the time from the date of randomization to the date of death of the subject.
Time Frame
Up to approximately 3 years
Secondary Outcome Measure Information:
Title
Objective remission rate (ORR)
Description
The objective response rate will be mainly analyzed by the independent efficacy evaluation committee according to the RECIST 1.1 standard tumor evaluation (the evaluation by the investigator will also be performed).
Time Frame
Up to approximately 3 years
Title
Progression-free survival (PFS), evaluated by the investigator
Description
Progression-free survival (PFS) refers to the time from the date of randomization to the first researcher's evaluation of disease progression or death (calculated by the event that occurred first). The disease progression will be evaluated by the researchers according to the RECIST 1.1 standard.
Time Frame
Up to approximately 3 years
Title
Duration of relief (DOR)
Description
DOR is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death
Time Frame
Up to approximately 3 years
Title
Disease control rate (DCR)
Description
Disease control rate (DCR) is defined as cases where objective remission (assessed as complete remission or partial remission according to RECIST 1.1 standard) or stable disease during the study.
Time Frame
Up to approximately 3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Expected survival ≥12 weeks.
Locally advanced unresectable or metastatic UC with histopathological confirmation, including UC originating from the renal pelvis, ureters, bladder, or urethra.
Participants must not have received prior systemic therapy for locally advanced or metastatic urothelial carcinoma with the following exceptions:
Participants that received neoadjuvant chemotherapy with recurrence >6 months from completion of therapy are permitted; Participants that received adjuvant chemotherapy following cystectomy with recurrence >6 months from completion of therapy are permitted.
At least one measurable lesion based on RECIST version 1.1
HER2-expressing status determined by the central laboratory to be IHC 1+, 2+ or 3+.
ECOG performance status score: 0 or 1.
Adequate cardiac, bone marrow, hepatic, renal, and coagulation functions.
Exclusion Criteria:
Known hypersensitivity to RC48-ADC or Toripalimab or any of its components.
History of major surgery within 4 weeks of planned start of trial treatment.
Toxicity from a previous treatment has not returned to Grade 0-1.
Prior ADCs or PD-1/PD-L1 inhibitor therapy.
Active central nervous system (CNS) metastases.
Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection.
History of other malignancy within the previous 5 years, except for low-risk localized prostate cancer, appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or cancers with a similar curative outcome as those mentioned above.
Other serious, uncontrolled concomitant diseases that may affect protocol compliance or interpretation of outcomes, including active opportunistic infections or advanced (severe) infections, or uncontrolled diabetes.
Active autoimmune diseases that require systemic therapy over the past 2 years. Replacement therapies (such as thyroxine, insulin, or physiological replacement of glucocorticoids due to renal or pituitary deficiency) are allowed.
Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jianmin Fang, PhD
Phone
+86-010-58075561
Email
jianminfang@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Na Su, PhD
Organizational Affiliation
RemeGen Co., Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Cancer Hospital Chinese Academy of Medical Sciences
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aiping zhou
Facility Name
Beijing Cancer Hospital
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jun Guo
12. IPD Sharing Statement
Learn more about this trial
A Study of RC48-ADC Combined With Toripalimab For First-line Treatment of Urothelial Carcinoma
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