Adjuvant disitamab vedotin plus radiotherapy for HER2‑overexpressing upper urinary tract urothelial carcinoma with high recurrence risk

A Clinical Study of the Efficacy and Safety of Disitamab Vedotin in Combination With Radiotherapy for the Adjuvant Treatment of HER2 Overexpressing UTUC Patients With High Risk Factors for Recurrence After Radical Surgery

This study will try whether adding disitamab vedotin to radiotherapy after surgery helps people with HER2‑positive upper urinary tract urothelial carcinoma who are at high risk of recurrence.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Peking University First Hospital (Academic / other)
• Drugs / interventions: vedicilumab, prednisone, vedicloxacinumab
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06210490 on ClinicalTrials.gov

What this trial studies

This is a phase 2, single-center study enrolling 60 patients with HER2‑overexpressing upper urinary tract urothelial carcinoma and high-risk features after radical surgery. Participants choose Cohort I (adjuvant disitamab vedotin combined with radiotherapy for a planned 6 months of drug treatment) or Cohort II (close observation and best supportive care). Safety checks occur before each dose and until 30 days after the last dose, and effectiveness is monitored with imaging every 12 weeks until recurrence. The trial is conducted at Peking University First Hospital and focuses on cisplatin-ineligible patients or those not receiving platinum-based adjuvant therapy.

Who should consider this trial

Good fit: Adults (≥18 years) with pathologically confirmed upper urinary tract urothelial carcinoma after radical surgery, HER2 IHC 2+ or 3+, high‑risk pathological features (e.g., pT2 with additional high‑risk factors, pT3–pT4, or pN+), cisplatin‑ineligible or not receiving platinum adjuvant therapy, ECOG 0–1, and adequate organ function are ideal candidates.

Not a fit: Patients with HER2‑negative tumors, imaging‑confirmed metastatic disease, those who are eligible for and receive standard platinum‑based adjuvant chemotherapy, or patients with poor performance status or very limited life expectancy are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, the combination could lower the risk of recurrence after surgery and provide an effective non‑platinum adjuvant option for HER2‑overexpressing UTUC patients.

How similar studies have performed: HER2‑targeting antibody‑drug conjugates, including disitamab vedotin, have shown clinical activity in HER2‑positive urothelial cancers, but combining disitamab vedotin with adjuvant radiotherapy in high‑risk UTUC is a relatively novel approach without large prior confirmation.

Eligibility criteria

Inclusion Criteria:

1. Voluntary enrollment and signing of written informed consent;
2. Age ≥ 18 years, male or female;
3. Pathologically confirmed UTUC with at least any one of the following conditions: ① pT2 (need to be combined with at least simultaneous G3/high-grade tumor multiple, multifocal positive margins and one of the high-risk recurrence factors); ② pT3 to pT4; ③ pN+;
4. Cisplatin intolerance or not receiving platinum-based drugs for adjuvant therapy;
5. No recurrent metastasis confirmed by imaging ≥4 weeks postoperatively;
6. HER2 immunohistochemistry (IHC) results of IHC 3+ or 2+, subject's previous test results (confirmed by the investigator), and study center results are acceptable;
7. Expected survival time ≥ 6 months;
8. Eastern Cooperative Oncology Group (ECOG) Physical Status (PS) score of 0 to 1;
9. Normal major organ function, i.e., fulfillment of the following criteria:

   * Routine blood tests (no blood transfusion and no G-CSF use within 14 days prior to screening): a) Hemoglobin ≥ 90 g/L; b) Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L; c) Leukocyte count ≥ 3.0 × 10\^9 /L; d) Platelet count ≥ 80 × 10\^9/L ②Blood biochemistry (no albumin use within 14 days prior to screening): a) Albumin ≥ 28 g/L; b) Total bilirubin ≤ 2 x upper limit of normal (ULN); c) Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 x ULN in the absence of liver metastases, and ALT, AST, and ALP ≤ 5 x ULN in the presence of liver metastases; d) Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 50 mL/min calculated by the Cockcroft-Gault formula ③Coagulation: a) International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 x ULN; b) Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.

Exclusion Criteria:

1. A history of malignancy other than uroepithelial carcinoma, except in the following two cases: a) The patient has received potentially curative therapy and has had no evidence of the disease for 5 years; b) Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the uterine cervix, and other carcinomas in situ for which resection was successfully received;
2. Prior allogeneic stem cell or parenchymal organ transplantation;
3. Patients who have received other prior anti-tumor systemic therapy (including herbal medicine with anti-tumor indications) less than 4 weeks after completion of therapy and prior to dosing in this study, or who have not recovered from adverse events caused by prior therapy to ≤ CTCAE grade 1 (with the exception of alopecia and hyperpigmentation);
4. Prior or current congenital or acquired immunodeficiency disease;
5. Active or previously documented autoimmune or inflammatory diseases (including, but not limited to: autoimmune hepatitis, interstitial pneumonia, inflammatory bowel disease, systemic lupus erythematosus, vasculitis, uveitis, pituitary gland inflammation, hyper- or hypothyroidism, and asthma requiring bronchodilator therapy), with vitiligo, or asthma that has resolved completely in childhood and does not require any intervention in adulthood;
6. Treatment with systemic immunosuppressive medication within 2 weeks prior to enrollment or anticipated need for systemic immunosuppressive medication during the study period, with the exception of the following: a) Intranasal, inhaled, topical, or locally injected (e.g., intra-articular injection) corticosteroids; b) Systemic corticosteroids in doses not exceeding 10 mg/day of prednisone or other equivalent effect; c) Prophylactic corticosteroids for hypersensitivity reactions;
7. Patients with a known or suspected history of hypersensitivity to vedicilumab and similar drugs, or a history of hypersensitivity to chimeric or humanized antibodies or fusion proteins, or to excipients of the study drug;
8. Prior thrombosis or thromboembolic event within the previous 6 months, such as stroke and/or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc;
9. Patients assessed by a physician to be at risk for severe bleeding, including but not limited to severe bleeding (\> 30 ml within 3 months), hemoptysis (\> 5 ml within 4 weeks), with gastroscopy/assessment in the event of any of the above, whichever is based on the microscopic assessment or active bleeding or coagulation abnormality, with a propensity to hemorrhage or undergoing thrombolytic, anticoagulant, or antiplatelet therapy;
10. clinically significant cardiovascular disease including, but not limited to, acute myocardial infarction, severe/unstable angina or coronary artery bypass grafting within the previous 6 months, congestive heart failure (New York Heart Association NYHA classification \> grade 2), arrhythmias that are poorly controlled or require pacemaker therapy, hypertension that is uncontrolled by medications (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg);
11. Other significant clinical and laboratory abnormalities that, in the opinion of the investigator, compromise the safety evaluation, e.g., uncontrolled diabetes mellitus, chronic kidney disease, grade II or greater peripheral neuropathy (CTCAE V5.0), abnormal thyroid function;
12. Serious infections that are active or poorly controlled clinically active infections, including: a) Positive for the AIDS virus (HIV) (HIV1/2 antibodies); b) Active Hepatitis B (HBsAg positive or HBV DNA \> 2000 IU/ml and abnormal liver function); c) Active hepatitis C (HCV antibody positive or HCV RNA ≥103 copies/ml and abnormal liver function); d) Active tuberculosis; e) Other uncontrolled active infection (CTCAE V5.0 \> grade 2);
13. Not yet recovered from surgery, e.g. presence of unhealed incisions or serious postoperative complications;
14. Women who are pregnant or breastfeeding, and female or male patients of childbearing potential who are unwilling or unable to use effective contraception;
15. other conditions that the investigator deems inappropriate for inclusion.

Where this trial is running

Beijing, Beijing Municipality

• Peking University First Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Xuesong Li

Conditions Upper Urinary Tract Urothelial Carcinoma