Using Tislelizumab and Disitamab-vedotin for Neoadjuvant Therapy in High-risk Upper Tract Urothelial Carcinoma

A Single-arm, Open Clinical Trial of Efficacy and Safety of Tislelizumab in Combination With Disitamab-vedotin as Neoadjuvant Therapy for HER2-positive High-risk Upper Tract Urothelial Carcinoma (UTUC)

This study is testing a new combination of two drugs, tislelizumab and disitamab-vedotin, to see if they can safely help people with high-risk upper tract urothelial carcinoma before surgery, especially for those who can't take traditional chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 21 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tianjin Medical University Second Hospital (Academic / other)
• Drugs / interventions: tislelizumab, disitamab, immunotherapy, chemotherapy
• Locations: 1 site (Tianjin)
• Trial ID: NCT05837806 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy and safety of combining tislelizumab, an immunotherapy drug, with disitamab-vedotin as a neoadjuvant treatment for patients with high-risk upper tract urothelial carcinoma (UTUC). The study aims to provide an alternative to traditional chemotherapy, particularly for patients who may not tolerate cisplatin due to renal function concerns. Participants will undergo a series of preoperative treatments to assess the feasibility and safety of this novel immunotherapy regimen. The trial will include various assessments, including blood and tissue examinations to evaluate treatment response.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older diagnosed with high-risk upper uroepithelial carcinoma and meeting specific health criteria.

Not a fit: Patients with lower-stage UTUC or those who do not meet the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could offer a more effective and safer treatment option for patients with high-risk UTUC who are ineligible for standard chemotherapy.

How similar studies have performed: While the combination of immunotherapy and targeted therapy is a growing area of interest, this specific approach in UTUC is relatively novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Radiographically(CT, MRI or PET-CT, etc.) and histologically confirmed diagnosis of localized HER-2 expressing upper urothelial carcinoma( (cT1-4N0-2M0, HER-2 immunohistochemistry (IHC) ≥ 1+); high risk disease (according to EAU Guidelines for UTUC); planning to receive radical nephroureterectomy (RNU), distal ureterectomy (DU) or ureteroscopic ablation (UA).
2. Male or female aged 18 years and above;
3. Expected survival time greater than 12 weeks;
4. An ECOG status score of 0-2;
5. Agree to provide specimens of blood, urine, and tissue examination (for detection of MRD, PD-L1 expression, HER2 expression, tumor mutation load, immunohistochemistry, DNA and RNA detection, etc.);
6. The level of organ function must meet the following requirements:

   * hematological indicators: absolute neutrophil count ≥ 1.5 × 10\^9/L, platelet count ≥ 80 × 10\^9/L, hemoglobin ≥ 6.0 g/dL (can be maintained by symptomatic treatment)
   * hepatic function: total bilirubin ≤ 1.5 times the upper limit of normal, and glutathione and glutamic oxalacetic transaminase ≤ 2.5 times the upper limit of normal;
   * renal function: GFR ≥ 15 ml/min;
   * Subjects voluntarily joined the study, signed an informed consent form, were compliant, and cooperated with the follow-up.

Exclusion Criteria:

1. Live attenuated vaccines, other than COVID-19 vaccine, received within 4 weeks prior to treatment or scheduled to be received during the study period
2. Active, known or suspected autoimmune disease;
3. Known history of primary immunodeficiency;
4. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation
5. Female patients who are pregnant or breastfeeding
6. Untreated acute or chronic active hepatitis B or C infection. Patients who are receiving antiviral therapy with monitoring of viral copy number and are eligible for enrollment as determined by the physician on an individual patient basis;
7. Previous use of immunosuppressive drugs, excluding nasal spray and inhaled corticosteroids or physiologic doses of systemic steroids (i.e., no more than 10 mg/day prednisolone or equivalent pharmacologic physiologic doses of other corticosteroids), within 4 weeks prior to initiation of therapy
8. Known or suspected allergy history to tislelizumab and disitamab vedotin.
9. With a clear history of active tuberculosis.
10. Prior PD-1/PD-L1/CTLA-4 antibody or other immunotherapy;
11. Those who are participating in other clinical studies
12. Men of reproductive potential or women with the potential to become pregnant who are not using reliable contraception
13. Uncontrolled co-morbidities, including but not limited to

    * HIV-infected individuals (HIV-positive);
    * Severe infections that are active or poorly controlled clinically (including patients in the period of neocoronavirus infection)
    * Evidence of the presence of severe or uncontrolled systemic disease (e.g., severe psychiatric, neurological disease, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, hepatic or renal disease, uncontrolled hypertension \[i.e., defined as greater than or equal to CTCAE grade 2 hypertension despite medication\]).

Where this trial is running

Tianjin

• The Second Hospital of Tianjin Medical University — Tianjin, China (Recruiting)

Study contacts

• Principal investigator: Hailong Hu, MD,PhD — Tianjin Medical University Second Hospital
• Study coordinator: Hailong Hu, MD,PhD

Conditions Neoadjuvant Immunotherapy; neoadjuvant therapy; UTUC; immunotherapy; upper tract urothelial carcinoma; PD-1; ADC