A Clinical Trial Evaluating the Efficacy and Safety of Disitamab Vedotin Plus Tislelizumab Combined with Re-TURBT in the Treatment of HER-2-high Expression(2+-3+) Non-muscle Invasive Bladder Cancer At High-risk and Very High-risk.

NCT06630871 | Not Yet Recruiting Phase 2

• 1 other identifier: 2024YF042-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, multicenter, single-arm phase II trial aims to evaluate the clinical efficacy and safety of the combination therapy of Disitamab Vedotin with Tislelizumab and a second transurethral resection for the treatment of high-risk, very high-risk NMIBC with HER2 2+-3+.

Conditions

NMIBC

Outcome Measures

Primary Outcomes (1)

• 1-year Event-Free Survival rate

  The possibility of patients have not experienced any events for at least 12 months after receiving treatment, including death, disease progression, switch to chemotherapy, addition of other treatments, fatal or intolerable side effects, etc

  From date of randomization until the date of any event occurrence, whichever came first，assessed up to 12 months

Secondary Outcomes (7)

• 3-years Event-Free Survival rate

  From date of randomization until the date of any event occurrence, whichever came first，assessed up to 36 months

• 2-year bladder disease-free survival（2 year BIDFS） rate

  From date of randomization until the date of muscle-invasive recurrence, regional lymph node recurrence, distant metastasis, the need for radical cystectomy, or death, whichever came first，assessed up to 24 months

• Reccurence Free Survival（ RFS）

  From date of the first TURBT until the date of bladder tumor recurrence, assessed up to 36 months

• Overall survival

  From date of randomization until the date of death from any cause, assessed up to 60 months

• Time to complete bladder resection

  From date of randomization until the date of radical cystectomy, assessed up to 60 months

Study Arms (1)

Experimental group

EXPERIMENTAL

High risk and extremely high risk NMIBC for HER2 2 2+or 3+treated with combination therapy of trastuzumab, Distitamab Vedotin, and re-TURBt

Drug: Distitamab Vedotin in combination with Tislelizumab

Interventions

Distitamab Vedotin in combination with Tislelizumab DRUG

On the day after the initial TURBt procedure, use trastuzumab (200mg)+ Distitamab Vedotin (120mg \[≤ 60Kg\] or 2.0mg/Kg \[\>60Kg\]) every 3 weeks (Q3W). Simultaneously arrange for the patient to complete a second TURBt within 6 weeks, and continue to use 3 courses of Trastuzumab+Vediximab (Q3W) after surgery until the endpoint of 3-year follow-up

Also known as: surgery：re-TURBT

Experimental group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily participate in the experiment and sign a written informed consent form；
• Patients should be aged between 18 and 85 years, with no gender restrictions, no severe organ failure such as heart, lung, or brain, and an expected survival period of one year or more;
• Complete the relevant screening tests (routine blood test, coagulation function, liver and kidney function, infectious disease screening, 12-lead electrocardiogram, urinary system ultrasound, pelvic enhanced CT or MRI, and tissue pathology examination), and have no contraindications for TURBt surgery;
• Eastern Cooperative Oncology Group (ECOG) score: 0-2 points;
• Previous systemic therapy without systemic immunity/ADC drugs；
• Histologically confirmed non muscle invasive bladder cancer (NMIBC), with or without carcinoma in situ (CIS), the main pathological type is urothelial carcinoma, including other specific histopathological types, but urothelial carcinoma dominates (at least 50%). Patients with AUA classification of high-risk and extremely high-risk recurrence or progression risk by the American Urological Association, and with immunohistochemical results of Her2 being 3+or 2+, who have undergone maximal TURBt within 6 weeks.

You may not qualify if:

• Any of the following circumstances: those with immune deficiency or impairment (such as AIDS patients), who are using immunosuppressive drugs or radiotherapy, and who may cause systemic BCG disease reaction; Individuals who are allergic to the components of BCG vaccine; Patients with fever and acute infectious diseases, including active tuberculosis, or those receiving anti tuberculosis treatment; Accompanied by severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease;
• Patients with other urogenital system tumors or other organ tumors;
• Patients with AUA grading of low-risk, moderate risk NMIBC, or myometrial invasive bladder urothelial carcinoma (T2 stage or above), or immunohistochemistry Her2 negative or 1+patients;
• Individuals who have received chemotherapy, radiation therapy, or immunotherapy within the past 4 weeks;
• Pregnant or lactating women, women of childbearing age who have not taken effective contraceptive measures, and those planning to conceive during the trial period (including male subject partners);
• Patients with severe urethral stricture who cannot undergo cystoscopy, those with a history of bladder contracture or functional bladder volume less than 100mL;
• Patients with various mental disorders, severe coagulation function, liver and kidney function, hematopoietic dysfunction, etc. who cannot tolerate surgical treatment;
• Participated in clinical trials of other drugs within the past 3 months prior to enrollment;
• Known opioid or alcohol dependent individuals;
• Researchers believe that there may be any situation that increases the risk to participants or interferes with the execution of clinical trials.

Sponsors & Collaborators

• Fujian Medical University Union Hospital: lead
• BeiGene: collaborator
• RemeGen Co., Ltd.: collaborator

Study Sites (1)

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

Location

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms

Interventions

tislelizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Central Study Contacts

Jianhui Chen

CONTACT

86-13055726039; chenjianhui1983@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2024
• First Posted: October 8, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2028
• Last Updated: October 10, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)