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

Overview

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.

Full Title of Study: “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

• Study Type: Interventional
• Study Design
  • Allocation: Non-Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Treatment
  • Masking: None (Open Label)
• Study Primary Completion Date: February 2025

Interventions

• 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.
• Drug: Disitamab Vedotin
  • Disitamab Vedotin

Arms, Groups and Cohorts

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

Clinical Trial Outcome Measures

Primary Measures

• Complete Response (CR) Rate
  • Time Frame: At the time of transurethral resection biopsy (within 9 or 12 weeks of the first dose of disitamab vedotin)

Secondary Measures

• Progress Free Survival（PFS）
  • Time Frame: up to 3 years
• Recurrence Free Survival（RFS）
  • Time Frame: up to 3 years
• Cystectomy-Free Survival (CFS)
  • Time Frame: up to 3 years
  • defined from D1 of treatment until cystectomy
• Duration of Response (DOR)
  • Time Frame: up to 3 years
• Event-Free Survival（EFS）
  • Time Frame: 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)
  • Time Frame: 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
  • Time Frame: up to 3 years
• PD-1 expression status
  • Time Frame: up to 3 years

Participating in This Clinical Trial

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 >= 1.5×10^9/L, platelet count >= 100×10^9/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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Tianjin Medical University Second Hospital
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • Hailong Hu, Principal Investigator, Tianjin Medical University Second Hospital
• Overall Contact(s)
  • Hailong Hu, +86-13662096232, hhllove2004@163.com