Combination treatment for high-risk bladder cancer

An Open Label, Phase 2 Study of Disitamab Vedotin Combined With Tislelizumab for Patients With Her2 Overexpressing (IHC2+ or 3+) High-Risk Non-Muscle-Invasive Urothelial Bladder Carcinoma Which is Not Completely Resectable

This study is testing a new combination treatment for people with high-risk bladder cancer that can't be fully removed to see if it helps them better than current options.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 176 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tianjin Medical University Second Hospital (Academic / other)
• Drugs / interventions: disitamab, tislelizumab
• Locations: 1 site (Tianjin, Tianjin)
• Trial ID: NCT05495724 on ClinicalTrials.gov

What this trial studies

This phase II study evaluates the safety and efficacy of Disitamab Vedotin combined with Tislelizumab for patients with Her2 overexpressing high-risk non-muscle-invasive bladder cancer that cannot be completely resected. Participants will receive the treatment every three weeks for four cycles over a 12-week period, followed by a transurethral resection biopsy. The study aims to determine how well this combination therapy works in this specific patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with Her2 overexpressing high-risk non-muscle-invasive urothelial carcinoma that is not completely resectable.

Not a fit: Patients with low-risk bladder cancer or those whose tumors are completely resectable may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with high-risk bladder cancer that is not amenable to complete surgical removal.

How similar studies have performed: While this approach is innovative, similar studies have shown promise in targeting Her2 overexpressing cancers, suggesting potential for success.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years;
2. Urothelial carcinoma with Her2 IHC 2+ or 3+;
3. High-risk non-muscle-invasive urothelial carcinoma or high-risk non-muscle-invasive urothelial carcinoma as the main pathological component \> 50%, difined as following:

   a. T1 b. High-grade Ta c.Carcinoma in situ(CIS);
4. Multi-point biopsy of bladder shows there are more than 2 section and over 3 points of pathological specimens are diagnosed as above, meanwhile, the tumor has to be diagnosed as not completely resectable by at least 2 senior urologist;
5. Agreed to provide tissue examination samples (for detection of PD-L1 expression, tumor mutation load, IHC, detection of DNA and RNA, etc;)
6. Organ function level must meet or under the support treatment meet the following requirements:

   * Hematological indexes: neutrophil count \>= 1.5x10\^9/L, platelet count \>= 100x10\^9/L, hemoglobin \>= 9.0 g/dl;
   * Liver function: total bilirubin \<=1.5 ULN, alanine aminotransferase and aspartate aminotransferase \<=2.5 ULN（patient with metastatic liver cancer：aminotransferase \<=5.0 ULN）;
   * Renal function: creatinine ≤ 1.5 times the upper limit of normal, and creatinine clearance ≥ 50 ml/min;
7. The subjects volunteered to join the study, signed informed consent, and had good compliance with follow-up;

Exclusion Criteria:

1. Active, known or suspected autoimmune diseases;
2. History of primary immunodeficiency;
3. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
4. Pregnant or lactating female patients;
5. Untreated acute or chronic active hepatitis B or hepatitis C infection. Under the condition of monitoring the virus copy number of patients receiving antiviral treatment, doctors can judge whether they are in line with the patients' individual conditions;
6. Prior use of immunosuppressive drugs within 4 weeks prior to the start of treatment, excluding nasal and inhaled corticosteroids or physiological doses of systemic steroids (i.e. not more than 10 mg / day prednisolone or other corticosteroids with the same physiological dose);
7. Known or suspected allergy to disitamab vedotin or tislelizumab;
8. Have a clear history of active tuberculosis;
9. Participating in other clinical researchers;
10. Men with reproductive capacity or women who are likely to become pregnant do not take reliable contraceptive measures;
11. Uncontrolled concurrent diseases, including but not limited to:

    * HIV infected (HIV antibody positive);
    * Severe infection in active stage or poorly controlled;
    * Evidence of serious or uncontrollable systemic diseases (such as severe mental, neurological, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, liver or kidney diseases, uncontrolled hypertension \[i.e. hypertension greater than or equal to CTCAE grade 2 after drug treatment\]);
    * Patients with active bleeding or new thrombotic disease

Where this trial is running

Tianjin, Tianjin

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

Study contacts

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

Conditions Her2 Overexpressing High-Risk Non-Muscle Invasive Bladder Urothelial Carcinoma; Disitamab Vedotin; Tislelizumab