NECTAR Study: Neoadjuvant Toripalimab + 9MW2821 for Local UTUC

Official title

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)

Overview

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

• 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.
• 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.

Primary outcome measures

• Percentage of Participants With Pathologic Complete Response (pCR) [Time frame: At the time of surgery (radical nephroureterectomy with or without lymph node dissection).]

Secondary outcome measures (7)

• Objective Response Rate (ORR) [Time frame: At the time of surgery or last preoperative imaging assessment.]
• 1-year Event-Free Survival (EFS) [Time frame: From randomization up to 1 year.]
• Percentage of Participants With Pathologic Downstaging (pDS) [Time frame: At the time of surgery (radical nephroureterectomy with or without lymph node dissection).]
• Disease-Free Survival (DFS) [Time frame: From the date of surgery through study completion (up to 3 years).]
• Overall Survival (OS) [Time frame: From randomization through study completion (up to 3 years).]
• Incidence of Adverse Events [Time frame: From first dose of study treatment through 90 days after treatment.]
• Perioperative Complications [Time frame: From the start of surgery through 90 days after surgery.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking University Third Hospital — Beijing

Identifiers

NCT: NCT07412171 · LM2026029 · IRB00006761 · M20250851

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗