Her2 Overexpressing High-Risk Non-Muscle Invasive Bladder Urothelial Carcinoma
Conditions
Keywords
Disitamab Vedotin, Tislelizumab
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.
Interventions
DRUGDisitamab 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.
DRUGDisitamab Vedotin
Disitamab Vedotin
Sponsors
Tianjin Medical University Second Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Complete Response (CR) Rate | At the time of transurethral resection biopsy (within 9 or 12 weeks of the first dose of disitamab vedotin) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Progress Free Survival（PFS） | up to 3 years | — |
| 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 | — |
| 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 |
Countries
China
Contacts
Primary ContactHailong Hu
Outcome results
None listed