NECTAR Study: Neoadjuvant Toripalimab + 9MW2821 for Local UTUC (NECTAR)

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)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Upper Tract Urothelial Carcinoma
• Intervention / Treatment: Drug: Toripalimab; Drug: 9MW2821; Procedure: Radical Nephroureterectomy with or without Lymph Node Dissection

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100191
      • Peking University Third Hospital
      • Contact: Clinical Trial Office; Phone Number: +86 10 8226 5573; Email: bysy@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant Toripalimab + 9MW2821; Participants receive neoadjuvant toripalimab plus 9MW2821 followed by radical nephroureterectomy with or without lymph node dissection.	Drug: Toripalimab; Toripalimab is administered intravenously at a dose of 240 mg every 3 weeks for 3 cycles as neoadjuvant therapy prior to surgery.; Drug: 9MW2821; 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.
Active Comparator: Upfront Surgery (SOC); Participants undergo upfront radical nephroureterectomy with or without lymph node dissection according to standard of care.	Procedure: Radical Nephroureterectomy with or without Lymph Node Dissection; Participants undergo radical nephroureterectomy with or without lymph node dissection according to institutional standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Pathologic Complete Response (pCR)	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.	At the time of surgery (radical nephroureterectomy with or without lymph node dissection).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	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.	At the time of surgery or last preoperative imaging assessment.
1-year Event-Free Survival (EFS)	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.	From randomization up to 1 year.
Percentage of Participants With Pathologic Downstaging (pDS)	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.	At the time of surgery (radical nephroureterectomy with or without lymph node dissection).
Disease-Free Survival (DFS)	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.	From the date of surgery through study completion (up to 3 years).
Overall Survival (OS)	Overall survival (OS) is defined as the time from randomization to death from any cause.	From randomization through study completion (up to 3 years).
Incidence of Adverse Events	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.	From first dose of study treatment through 90 days after treatment.
Perioperative Complications	Perioperative complications are defined as intraoperative and postoperative complications directly attributable to the surgical procedure or perioperative management.	From the start of surgery through 90 days after surgery.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-Reported Outcomes (PROs)	Patient-reported outcomes (PROs) are assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). The EORTC QLQ-C30 is a validated, cancer-specific questionnaire that includes a Global Health Status/Quality of Life scale and multiple functional and symptom scales, including Physical Functioning. All EORTC QLQ-C30 scale scores range from 0 to 100. For the Global Health Status/Quality of Life and functional scales, higher scores indicate better quality of life or functioning. For symptom scales, higher scores indicate greater symptom burden. Changes from baseline in PRO scores are summarized to describe symptom burden, functional status, and health-related quality of life over time.	From baseline through up to 36 months.

Collaborators and Investigators

• Sponsor: Peking University Third Hospital
• Collaborators: Beijing Friendship Hospital; Peking University Cancer Hospital & Institute; The First Affiliated Hospital of Zhengzhou University; The Second Affiliated Hospital of Kunming Medical University; Jiangsu Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: January 21, 2026
• First Submitted That Met QC Criteria: February 13, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Neoadjuvant Therapy; Phase II; UTUC; Toripalimab; Pathologic Complete Response; Radical Nephroureterectomy; 9MW2821
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Disease Progression; Pathological Conditions, Signs and Symptoms; Pathologic Complete Response; Surgical Procedures, Operative; toripalimab; Lymph Node Excision
• Other Study ID Numbers: LM2026029; IRB00006761 (Other Identifier: Peking University Third Hospital Medical Science Research Ethics Committee); M20250851 (Other Identifier: Peking University Third Hospital Medical Science Research Ethics Committee)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual participant data (IPD) sharing has not been determined at this time. Decisions regarding IPD sharing will be made in accordance with applicable regulations, institutional policies, and sponsor agreements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No