NECTAR Study: Neoadjuvant Toripalimab + 9MW2821 for Local UTUC

Phase 2Not Yet RecruitingNCT07412171

Peking University Third Hospital40 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Upper Tract Urothelial Carcinoma

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: At the time of surgery (radical nephroureterectomy with or without lymph node dissection).

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: From the start of surgery through 90 days after surgery.