Clinical trial NCT05495724: Disitamab Vedotin Combined With Tislelizumab for Her2 Overexpressing High-Risk Non-Muscle-Invasive Urothelial Bladder Carcinoma Which is Not Completely Resectable
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Her2 Overexpressing High-Risk Non-Muscle Invasive Bladder Urothelial Carcinoma
Keywords: Disitamab Vedotin
Tislelizumab
Lead sponsor: Tianjin Medical University Second Hospital
Sponsor class: OTHER
First posted: 2022-08-10
Enrollment: 176
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase II study to determine the safety and efficacy of Disitamab Vedotin when given in combination with Tislelizumab as treatment for patients with Her2 overexpressing high-risk non-muscle-invasive bladder cancer (HR NMIBC) which is not completely resectable. Patients will receive treatment with Disitamab Vedotin in combination with tislelizumab every 3 weeks for 4 treatment cycles over 12 weeks followed by transurethral resection biopsy.


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

Primary outcomes:
measure: Complete Response (CR) Rate
timeFrame: At the time of transurethral resection biopsy (within 9 or 12 weeks of the first dose of disitamab vedotin)
Secondary outcomes:
measure: Progress Free Survival（PFS）
timeFrame: up to 3 years
measure: Recurrence Free Survival（RFS）
timeFrame: up to 3 years
measure: Cystectomy-Free Survival (CFS)
timeFrame: up to 3 years
measure: Duration of Response (DOR)
timeFrame: up to 3 years
measure: Event-Free Survival（EFS）
timeFrame: up to 3 years
measure: Number of adverse events and severity by grade (CTCAE)
timeFrame: 12 weeks of treatment plus 30 days for toxicity followup
measure: Her2 status
timeFrame: up to 3 years
measure: PD-1 expression status
timeFrame: up to 3 years
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University Second Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Medical University Second Hospital
name: Hailong Hu
role: PRINCIPAL_INVESTIGATOR
References: