NECTAR Study: Neoadjuvant Toripalimab + 9MW2821 for Local UTUC

NCT07412171 | Not Yet Recruiting Phase 2 DMC

• 3 other identifiers: LM2026029IRB00006761M20250851
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Upper Tract Urothelial Carcinoma

Keywords

UTUC; Toripalimab; 9MW2821; Neoadjuvant Therapy; Radical Nephroureterectomy; Immunotherapy; Phase II; Pathologic Complete Response

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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).

Other Outcomes (1)

• Patient-Reported Outcomes (PROs)

  From baseline through up to 36 months.

Study Arms (2)

Neoadjuvant Toripalimab + 9MW2821

EXPERIMENTAL

Participants receive neoadjuvant toripalimab plus 9MW2821 followed by radical nephroureterectomy with or without lymph node dissection.

Drug: Toripalimab; Drug: 9MW2821

Upfront Surgery (SOC)

ACTIVE COMPARATOR

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

Interventions

Toripalimab DRUG

Toripalimab is administered intravenously at a dose of 240 mg every 3 weeks for 3 cycles as neoadjuvant therapy prior to surgery.

Neoadjuvant Toripalimab + 9MW2821

9MW2821 DRUG

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.

Neoadjuvant Toripalimab + 9MW2821

Radical Nephroureterectomy with or without Lymph Node Dissection PROCEDURE

Participants undergo radical nephroureterectomy with or without lymph node dissection according to institutional standard of care.

Upfront Surgery (SOC)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

Location

MeSH Terms

Conditions

Pathologic Complete Response

Interventions

toripalimab; Lymph Node Excision

Condition Hierarchy (Ancestors)

Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2026
• First Posted: February 17, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

CN (1)