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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 452
- 试验地点
- 2
- 主要终点
- Progression-free survival (PFS), evaluated by independent review committee
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Adequate cardiac, bone marrow, hepatic, renal, and coagulation functions.
排除标准
- •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-
- •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.
研究组 & 干预措施
RC48-ADC + JS001
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).
干预措施: RC48-ADC (Drug)
RC48-ADC + JS001
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).
干预措施: Toripalimab (Drug)
Gemcitabine + cisplatin/carboplatin
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).
干预措施: Gemcitabine (Drug)
Gemcitabine + cisplatin/carboplatin
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).
干预措施: Cisplatin (Drug)
Gemcitabine + cisplatin/carboplatin
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).
干预措施: Carboplatin (Drug)
结局指标
主要结局
Progression-free survival (PFS), evaluated by independent review committee
时间窗: Up to approximately 3 years
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)
时间窗: Up to approximately 3 years
Overall survival (OS) refers to the time from the date of randomization to the date of death of the subject.
次要结局
- Disease control rate (DCR)(Up to approximately 3 years)
- Duration of relief (DOR)(Up to approximately 3 years)
- Objective remission rate (ORR)(Up to approximately 3 years)
- Progression-free survival (PFS), evaluated by the investigator(Up to approximately 3 years)