Disitamab Vedotin Combined With Tislelizumab for Her2 Overexpressing High-Risk Non-Muscle-Invasive Urothelial Bladder Carcinoma Which is Not Completely Resectable
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: 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.
Other Names:
|
| Other: Disitamab Vedotin Disitamab Vedotin 120mg IV on day 1 every 3 weeks for 3 or 4 cycles followed by transurethral resection biopsy. |
Drug: Disitamab Vedotin
Disitamab Vedotin
|
Outcome Measures
Primary Outcome Measures
- Complete Response (CR) Rate [At the time of transurethral resection biopsy (within 9 or 12 weeks of the first dose of disitamab vedotin)]
Secondary Outcome Measures
- Progress Free Survival（PFS） [up to 3 years]
- Recurrence Free Survival（RFS） [up to 3 years]
- Cystectomy-Free Survival (CFS) [up to 3 years]
defined from D1 of treatment until cystectomy
- Duration of Response (DOR) [up to 3 years]
- Event-Free Survival（EFS） [up to 3 years]
defined from D1 of treatment until the time of any events，included progressive disease，discontinue treatment for any cause or death
- Number of adverse events and severity by grade (CTCAE) [12 weeks of treatment plus 30 days for toxicity followup]
Safety and toxicity will be characterized according to the reported adverse event (AE) profile using NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0, as well as a patient questionnaire derived from the Patient Reported Outcomes (PRO)-CTCAE and Patient Reported Outcomes Measurement Information System (PROMIS).
- Her2 status [up to 3 years]
- PD-1 expression status [up to 3 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age ≥ 18 years;
-
Urothelial carcinoma with Her2 IHC 2+ or 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:
- T1 b. High-grade Ta c.Carcinoma in situ(CIS);
-
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;
-
Agreed to provide tissue examination samples (for detection of PD-L1 expression, tumor mutation load, IHC, detection of DNA and RNA, etc;)
-
Organ function level must meet or under the support treatment meet the following requirements:
-
Hematological indexes: neutrophil count >= 1.5x109/L, platelet count >= 100x109/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;
- The subjects volunteered to join the study, signed informed consent, and had good compliance with follow-up;
Exclusion Criteria:
-
Active, known or suspected autoimmune diseases;
-
History of primary immunodeficiency;
-
Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
-
Pregnant or lactating female patients;
-
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;
-
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);
-
Known or suspected allergy to disitamab vedotin or tislelizumab;
-
Have a clear history of active tuberculosis;
-
Participating in other clinical researchers;
-
Men with reproductive capacity or women who are likely to become pregnant do not take reliable contraceptive measures;
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tianjin Medical University Second Hospital | Tianjin | Tianjin | China | 300211 |
Sponsors and Collaborators
- Tianjin Medical University Second Hospital
Investigators
- Principal Investigator: Hailong Hu, Tianjin Medical University Second Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TRUCE-04