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

NCT ID: NCT05495724

Last Updated: 2022-08-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 176 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-23
• Study Completion Date: 2025-07-31

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Disitamab Vedotin and Tislelizumab

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.

Group Type: EXPERIMENTAL

Disitamab Vedotin Tislelizumab

Intervention Type: DRUG

Disitamab Vedotin 120mg will be administered on Day 1 of each cycle for 4 treatment cycles;Tislelizumab 200mg will be administered on Day 2 of each cycle for 4 treatment cycles.

Disitamab Vedotin

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

Group Type: OTHER

Disitamab Vedotin

Intervention Type: DRUG

Disitamab Vedotin

Interventions

Disitamab Vedotin Tislelizumab

Disitamab Vedotin 120mg will be administered on Day 1 of each cycle for 4 treatment cycles;Tislelizumab 200mg will be administered on Day 2 of each cycle for 4 treatment cycles.

Intervention Type: DRUG

Disitamab Vedotin

Disitamab Vedotin

Intervention Type: DRUG

Other Intervention Names

KEYNOTE-057

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tianjin Medical University Second Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hailong Hu

Role: PRINCIPAL_INVESTIGATOR

Tianjin Medical University Second Hospital

Locations

Tianjin Medical University Second Hospital

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Hailong Hu

Role: CONTACT

hhllove2004@163.com

+86-13662096232

Facility Contacts

Hailong Hu

Role: primary

hhllove2004@163.com

+86-13662096232

Other Identifiers

TRUCE-04

Identifier Type: -

Identifier Source: org_study_id