NECTAR Study: A Multicenter, Open-label, Randomized Phase II Study of Neoadjuvant Toripalimab Plus 9MW2821 Versus Upfront Radical Nephroureterectomy With/Without Lymph Node Dissection in Patients With Local Upper Tract Urothelial Carcinoma (UTUC)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Pathologic Complete Response (pCR)
研究概览
简要总结
The NECTAR study is a multicenter, open-label, randomized phase II clinical trial designed to evaluate a neoadjuvant treatment strategy in patients with localized upper tract urothelial carcinoma (UTUC).
In this study, eligible participants will be randomly assigned to receive either neoadjuvant treatment with toripalimab plus the investigational drug 9MW2821 followed by radical nephroureterectomy with or without lymph node dissection, or upfront radical nephroureterectomy with or without lymph node dissection as standard of care. The purpose of the study is to compare the pathologic response at the time of surgery between the two treatment approaches and to assess treatment safety.
Participants will be monitored throughout treatment and follow-up for treatment response, adverse events, and other clinical outcomes. The information obtained from this study may help improve future treatment strategies for patients with localized UTUC.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 18 to 80 years, male or female.
- •Histologically confirmed upper tract urothelial carcinoma (UTUC) involving the renal pelvis and/or ureter, with predominant (≥50%) urothelial histology.
- •Treatment-naïve, non-metastatic disease (M0) with clinical stage T1-T3, as determined by imaging.
- •Eligible for and willing to undergo radical nephroureterectomy with or without lymph node dissection.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate hematologic, hepatic, renal, and cardiac function as defined by the protocol.
- •Availability of tumor tissue for biomarker analyses.
- •Ability to understand and willingness to sign a written informed consent document.
排除标准
- •Prior systemic anti-tumor therapy for urothelial carcinoma, except for intravesical therapy for non-muscle-invasive disease.
- •Prior treatment with a programmed cell death 1 (PD-1) inhibitor, programmed cell death ligand 1 or 2 (PD-L1/L2) inhibitor, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, or antibody-drug conjugate.
- •Evidence of metastatic disease (M1) or regional lymph node involvement of N2 or higher.
- •Prior systemic anticancer therapy, including investigational agents, within 3 years prior to study enrollment.
- •Prior radiotherapy to the bladder or upper urinary tract.
- •Active autoimmune disease requiring systemic treatment.
- •Active or uncontrolled infection, including known active hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) infection, or active tuberculosis.
- •Receipt of a live or live-attenuated vaccine within 30 days prior to the first dose of study treatment.
- •History of allogeneic tissue or solid organ transplantation.
- •Uncontrolled diabetes mellitus, defined as hemoglobin A1c ≥8%, or hemoglobin A1c ≥7% to <8% with associated diabetes-related symptoms.
- •Clinically significant cardiovascular disease or thromboembolic events that, in the investigator's judgment, would increase study risk.
- •Ongoing peripheral sensory or motor neuropathy of Grade 2 or higher.
- •Known psychiatric disorder or substance abuse that would interfere with study participation or compliance.
- •Pregnancy or breastfeeding.
- •Any other condition that, in the investigator's judgment, would make the participant unsuitable for the study.
研究组 & 干预措施
Neoadjuvant Toripalimab + 9MW2821
Participants receive neoadjuvant toripalimab plus 9MW2821 followed by radical nephroureterectomy with or without lymph node dissection.
干预措施: Toripalimab (Drug)
Neoadjuvant Toripalimab + 9MW2821
Participants receive neoadjuvant toripalimab plus 9MW2821 followed by radical nephroureterectomy with or without lymph node dissection.
干预措施: 9MW2821 (Drug)
Upfront Surgery (SOC)
Participants undergo upfront radical nephroureterectomy with or without lymph node dissection according to standard of care.
干预措施: Radical Nephroureterectomy with or without Lymph Node Dissection (Procedure)
结局指标
主要结局
Percentage of Participants With Pathologic Complete Response (pCR)
时间窗: At the time of surgery (radical nephroureterectomy with or without lymph node dissection).
Pathologic complete response (pCR) is defined as the absence of residual viable urothelial carcinoma in the resected primary tumor and sampled lymph nodes (e.g., ypT0N0) based on final surgical pathology following radical nephroureterectomy with or without lymph node dissection.
次要结局
- Objective Response Rate (ORR)(At the time of surgery or last preoperative imaging assessment.)
- 1-year Event-Free Survival (EFS)(From randomization up to 1 year.)
- Percentage of Participants With Pathologic Downstaging (pDS)(At the time of surgery (radical nephroureterectomy with or without lymph node dissection).)
- Disease-Free Survival (DFS)(From the date of surgery through study completion (up to 3 years).)
- Overall Survival (OS)(From randomization through study completion (up to 3 years).)
- Incidence of Adverse Events(From first dose of study treatment through 90 days after treatment.)
- Perioperative Complications(From the start of surgery through 90 days after surgery.)