Upper Tract Urothelial Carcinoma
Conditions
Keywords
UTUC, Toripalimab, 9MW2821, Neoadjuvant Therapy, Radical Nephroureterectomy, Immunotherapy, Phase II, Pathologic Complete Response
Brief summary
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.
Interventions
DRUGToripalimab
Toripalimab is administered intravenously at a dose of 240 mg every 3 weeks for 3 cycles as neoadjuvant therapy prior to surgery.
DRUG9MW2821
9MW2821 is administered intravenously at a dose of 1.25 mg/kg on Day 1 and Day 8 every 3 weeks for 3 cycles as neoadjuvant therapy.
PROCEDURERadical Nephroureterectomy with or without Lymph Node Dissection
Participants undergo radical nephroureterectomy with or without lymph node dissection according to institutional standard of care.
Sponsors
Peking University Third Hospital
Jiangsu Provincial People's Hospital
Peking University Cancer Hospital & Institute
Beijing Friendship Hospital
The First Affiliated Hospital of Zhengzhou University
The Second Affiliated Hospital of Kunming Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* 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 1. * 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Pathologic Complete Response (pCR) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | At the time of surgery or last preoperative imaging assessment. | Objective response rate (ORR) is defined as the proportion of participants who achieve a confirmed complete response (CR) or partial response (PR) based on radiographic assessment according to RECIST version 1.1. |
| 1-year Event-Free Survival (EFS) | From randomization up to 1 year. | Event-free survival (EFS) is defined as the time from randomization to the first occurrence of radiographic disease progression that precludes definitive surgery, failure to undergo surgery in participants with residual disease, gross residual disease at surgery, recurrence after surgery (local or distant), or death from any cause. |
| Percentage of Participants With Pathologic Downstaging (pDS) | At the time of surgery (radical nephroureterectomy with or without lymph node dissection). | Pathologic downstaging (pDS) is defined as a reduction in pathologic stage at the time of surgery compared with the baseline clinical stage, based on final surgical pathology. |
| Disease-Free Survival (DFS) | From the date of surgery through study completion (up to 3 years). | Disease-free survival (DFS) is defined as the time from radical nephroureterectomy with or without lymph node dissection to the first documented recurrence (local or distant) or death from any cause, whichever occurs first. |
| Overall Survival (OS) | From randomization through study completion (up to 3 years). | Overall survival (OS) is defined as the time from randomization to death from any cause. |
| Incidence of Adverse Events | From first dose of study treatment through 90 days after treatment. | Safety and tolerability are assessed by the incidence, nature, and severity of adverse events (AEs), including serious adverse events (SAEs) and adverse events leading to dose modification or discontinuation. Adverse events are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. |
| Perioperative Complications | From the start of surgery through 90 days after surgery. | Perioperative complications are defined as intraoperative and postoperative complications directly attributable to the surgical procedure or perioperative management. |
Countries
China
Outcome results
None listed