upper tract urothelial carcinoma
Conditions
Interventions
Cohort A:Neoadjuvant Therapy
Cycles C1–C3: Each cycle is 21 days.
9MW2821: 1.25 mg/kg, administered intravenously on Day 1 and Day 8 of each cycle.
Toripalimab: 240 mg, administered intravenously on D
Cohort B:Direct Surgical Treatment
Undergo radical nephroureterectomy.
Cohort C:Neoadjuvant Therapy
Cycles C1–C3: Each cycle is 21 days.
Toripalimab: 240 mg, administered intravenously on Days 7–14 of each cycle.
Radiotherapy: Short-course radiotherapy (SCRT): Single fra
administered on Day 1 of each cycle.
Sponsors
Peking University Third Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily agree to participate in the study and sign the informed consent form approved by the Ethics Committee. 2. At the time of signing the informed consent form, subjects must be aged =18 years and =80 years, with no restriction on sex. 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0–1. 4. Histopathologically confirmed upper tract urothelial carcinoma (UTUC), including renal pelvic carcinoma and ureteral carcinoma. Urothelial carcinoma with squamous differentiation, glandular differentiation, or mixed histology is also eligible, provided that the urothelial carcinoma component accounts for >50% in mixed tumors. 5. Imaging-confirmed non-metastatic urothelial carcinoma (M0) with a clinical stage of T1–3NxM0. Subjects must be assessed as suitable for and planned to undergo radical surgery, and be clinically evaluated as able to tolerate radiotherapy. 6. Provision of tumor tissue samples (at least 5 unstained slides, paraffin scrolls, paraffin blocks, or equivalent specimens). 7. An expected survival time of no less than 12 weeks. 8. Adequate organ function meeting the following criteria (based on the normal reference ranges of the study center; if the subject has recently received blood transfusions or growth factor therapy, hematologic testing must be performed =7 days after growth factor administration or =14 days after any blood transfusion): * Absolute neutrophil count (ANC) =1.5 × 10?/L * Platelet count (PLT) =100 × 10?/L * Hemoglobin (Hb) =90 g/L * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3 × upper limit of normal (ULN) * Total bilirubin =1.5 × ULN * International normalized ratio (INR) =1.5 × ULN * Creatinine clearance =30 mL/min (calculated using the Cockcroft–Gault formula) or serum creatinine =1.5 × ULN * Left ventricular ejection fraction (LVEF) =50% * QT interval corrected by Fridericia’s formula (QTcF) =480 ms 9. Male or female subjects must meet one of the following conditions: * Women of non-childbearing potential, defined as those who have undergone hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or who are postmenopausal; * Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first administration of the study drug (false-positive results may be enrolled after pregnancy is ruled out by the investigator), and must use effective contraception throughout the study period and for 180 days after the end of study treatment (e.g., dual-barrier contraception, condoms, oral or injectable contraceptives, intrauterine devices). Subjects with lactation capability must not breastfeed; * Male subjects must have undergone vasectomy or agree to use effective contraception during the study treatment period and for 180 days after the last dose of the study drug. 10. Be able to understand and comply with the protocol requirements, including scheduled visits, treatments, laboratory tests, and other study procedures.
Exclusion criteria
Exclusion criteria: 1. Prior systemic treatment for urothelial carcinoma, including radiotherapy, chemotherapy, targeted therapy, or other antitumor therapies (intravesical bladder instillation therapy is excluded). 2. Previous treatment with PD-1/PD-L1 inhibitors or antibody–drug conjugates (ADCs). 3. History of other malignancies within 3 years prior to the first administration of the study drug, except for cancers expected to be cured after radical treatment (such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, localized low-risk prostate cancer, papillary thyroid carcinoma, cervical carcinoma in situ, ductal carcinoma in situ of the breast, etc.). 4. Presence of active autoimmune diseases requiring systemic treatment (e.g., immunomodulatory drugs, corticosteroids, or immunosuppressants) within 2 years prior to the first administration of the study drug; or receipt of high-dose corticosteroids (>10 mg/day prednisone or equivalent, excluding prophylactic use) or other immunosuppressive agents within 14 days prior to the first administration of the study drug (replacement therapies such as thyroxine, insulin, or physiologic corticosteroid replacement are permitted). 5. Occurrence of severe arterial or venous thrombotic events or severe cardiovascular or cerebrovascular diseases within 1 year prior to the first administration of the study drug, including but not limited to myocardial infarction, unstable angina, pulmonary embolism, cerebral hemorrhage, cerebral infarction (excluding asymptomatic lacunar infarction not requiring clinical intervention), deep vein thrombosis, etc. 6. Major surgical procedures performed within 28 days prior to the first administration of the study drug; or cystoscopic/ureteroscopic biopsy or intravesical bladder instillation therapy performed within 7 days prior to the first administration of the study drug. 7. Peripheral neuropathy of grade =2. 8. Severe dry eye syndrome, active keratitis, corneal ulcer, or other conditions present prior to the first administration of the study drug that, in the investigator’s judgment, may increase the risk of corneal disease and render the subject unsuitable for participation in this study. 9. Active infections, including: * Positive hepatitis B surface antigen (HBsAg) with detectable HBV-DNA (=500 IU/mL); * Positive hepatitis C antibody (HCVAb) with detectable HCV-RNA; * Positive human immunodeficiency virus antibody (HIVAb); * Active Mycobacterium tuberculosis infection; * Other active infections requiring systemic treatment occurring within 7 days prior to the first administration of the study drug. 10. Other serious or uncontrolled diseases, including but not limited to: * Severe respiratory diseases (e.g., moderate to severe interstitial lung disease or obstructive pulmonary disease, severe asthma); * New York Heart Association (NYHA) class III or IV heart failure; * Glycated hemoglobin (HbA1c) =8% (subjects whose fasting blood glucose can be stably controlled to =10 mmol/L after pharmacologic treatment may be enrolled if deemed suitable by the investigator); * Poorly controlled hypertension (systolic blood pressure =160 mmHg and/or diastolic blood pressure =100 mmHg); * Large amounts of pleural effusion or ascites requiring symptomatic treatment within 14 days prior to the first administration of the study drug. 11. Receipt of any live vaccine within 28 days prior to the first administration of the study drug, or planned receipt of any live vac
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathological Complete Response (pCR) rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Clinical Objective Response Rate (cORR);Clinical Complete Response (cCR);Pathological Downstaging Rate (pDR);1-year Event-Free Survival (EFS) rate;Disease-Free Survival (DFS);Overall Survival (OS);Adverse Events (AEs) and Serious Adverse Events (SAEs); | — |
Countries
China
Contacts
Public ContactShudong Zhang
Peking University Third Hospital
Outcome results
None listed