Clinical trial NCT06378242: To Evaluate the Safety, Efficacy, and Pharmacokinetics of Intravesical Instiliations of Disitamab Vedotin in Patients With High-risk Non-muscular Invasive Bladder Cancer (NMIBC) That Express HER2
Official title: An Single-arm, Multicenter Phase I/II Clinical Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Intravesical Instiliations of Disitamab Vedotin in Patients With High-risk Non-muscular Invasive Bladder Cancer (NMIBC) That Express HER2
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: High-risk Non-muscle Invasive Bladder Cancer
Keywords: HER2-expression
High-risk non-muscle invasive bladder cancer
intravesical instiliations
Lead sponsor: RemeGen Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-04-22
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, efficacy, and pharmacokinetics of intravesical instiliations of Disitamab Vedotin in patients with high-risk non-muscular invasive bladder cancer (NMIBC) that express HER2

Detailed description: This is a single-arm, multicenter phase I/II clinical study to evaluate the safety, efficacy, and pharmacokinetics of intravesical instiliations of Disitamab Vedotin in patients with high-risk non-muscular invasive bladder cancer (NMIBC) that express HER2.

Eligibility criteria: Inclusion Criteria:

1. Voluntary consent to participate in the study and signed the informed consent form.
2. Male or female, age 18-75 years (including both).
3. Histologic confirmed non-muscle invasive bladder urothelial carcinoma (NMIBC), and the risk group met the high-risk (including very high-risk) group.

   Note: High-risk NMIBC is a high-grade / G3 tumor meeting any of the following:

   a.Carcinoma in situ (CIS) b. T1 stage c. diameter\>3cm d.Multiple tumors, or recurrent tumors.
4. Absence of resectable disease（Ta and/or T1 disease） after transurethral resection (TURBT) procedures (residual CIS acceptable;
5. The urologist assessed that radical surgery for bladder cancer was not suitable or the subject refused radical surgery for bladder cancer.
6. Tumor tissue samples were detected by immunohistochemistry (IHC) to satisfy HER2 expression of 1+, 2+ or 3+.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
8. Adequate heart, bone marrow, liver, kidney and coagulation function

Exclusion Criteria:

* 1. Invasive bladder cancer (T2 and above) and / or with regional lymph node and distant metastasis.

  2. Combined urothelial carcinoma outside the bladder (i. e., urethra, ureter or renal pelvis).

  3. Any other antitumor therapy received within 4 weeks before study administration, .

  4 Subjects plan to undergo major surgery during the study or within 4 weeks before the first dose.

  5, Known allergic to DV and its components or to any excipients.

Primary outcomes:
measure: Incidence of dose-limiting toxicity(DLT) (Phase I)
timeFrame: Approximately 21 days
measure: Incidence of Adverse event (Phase I)
timeFrame: Approximately 1 years
measure: Recommended Phase II Dose(RP2D)
timeFrame: Approximately 21 days
measure: Maximum Tolerated Dosage(MTD)
timeFrame: Approximately 21 days
Secondary outcomes:
measure: Disease-free survival (DFS) rates
timeFrame: Up to approximately 2 years
measure: Duration of response (DOR)
timeFrame: Up to approximately 2 years
measure: Disitamab Vedotin anti-drug antibody (ADA)
timeFrame: Up to approximately 2 years
measure: PK of enfortumab vedotin: Maximum concentration (Cmax)
timeFrame: Approximately 1 years
measure: PK of enfortumab vedotin: Trough concentration (Ctrough)
timeFrame: Approximately 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital,SunYat-sen University
state: Guangdong
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer hospital
state: Hunan
city: Nanjing
country: China
facility: The first affiliated hospital with nanjing medical universtity
state: Jiangsu
city: Chengdu
country: China
facility: West China Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Second Hospital
state: Tianjin
Study officials:
References: