Disitamab Vedotin Combined With Tislelizumab for Her2 Overexpressing High-Risk Non-Muscle-Invasive Urothelial Bladder Carcinoma Which is Not Completely Resectable

Tianjin Medical University Second Hospital

Status and phase: Enrolling; Phase 2

Conditions: Her2 Overexpressing High-Risk Non-Muscle Invasive Bladder Urothelial Carcinoma

Treatments: Drug: Disitamab Vedotin Tislelizumab; Drug: Disitamab Vedotin

Study type: Interventional

Funder types: Other

Identifiers

NCT05495724

TRUCE-04

Details and patient eligibility

About

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.

Enrollment: 176 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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176 participants in 2 patient groups

Disitamab Vedotin and Tislelizumab

Experimental group

Description:

Disitamab Vedotin 120mg IV on day 1 in combination with Tislelizumab 200mg IV on day 2 every 3 weeks for 3 or 4 cycles followed by transurethral resection biopsy.

Treatment:

Drug: Disitamab Vedotin Tislelizumab

Disitamab Vedotin

Other group

Description:

Disitamab Vedotin 120mg IV on day 1 every 3 weeks for 3 or 4 cycles followed by transurethral resection biopsy.

Treatment:

Drug: Disitamab Vedotin