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

Phase 1

Recruiting

• Conditions: High-risk Non-muscle Invasive Bladder Cancer
• Interventions: Drug: Disitamab Vedotin for injection

• Registration Number: NCT06378242
• Lead Sponsor: RemeGen Co., Ltd.

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.

Study Timeline

• Study First Submitted: 2024-04-12
• Study First Submitted QC: 2024-04-19
• Study First Posted: 2024-04-22
• Study Start: 2024-06-14
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-09
• Last Update Posted: 2024-07-11
• Primary Completion: 2029-03-15
• Study Completion: 2029-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Disitamab Vedotin Intravesical instiliations :Dose escalation cohort	Disitamab Vedotin for injection	Participants will receive Disitamab Vedotin for injection Intravesical instiliations into the bladder for 1 hour, D1, once a week.

Primary Outcome Measures

Name	Time	Method
Incidence of Adverse event (Phase I)	Approximately 1 years	According to the NCI CTCAE V5.0, to evaluate safety including adverse event rate and adverse event grade
Recommended Phase II Dose(RP2D)	Approximately 21 days	Assessed based on the Incidence of DLT
Incidence of dose-limiting toxicity(DLT) (Phase I)	Approximately 21 days
Maximum Tolerated Dosage(MTD)	Approximately 21 days	Assessed based on the Incidence of DLT

Secondary Outcome Measures

Name	Time	Method
Disitamab Vedotin anti-drug antibody (ADA)	Up to approximately 2 years	The number and proportion of anti-drug antibody (ADA)-positive subjects were analyzed according to dose group and time point.
PK of enfortumab vedotin: Maximum concentration (Cmax)	Approximately 1 years	Cmax will be recorded from the PK blood samples collected.
PK of enfortumab vedotin: Trough concentration (Ctrough)	Approximately 1 year	Ctrough will be recorded from the PK blood samples collected.
Duration of response (DOR)	Up to approximately 2 years	Defined as the time from the start of the first assessment of CR to the first assessment of high grade Ta, any grade of T1, new CIS, disease progression, cystectomy, or death from any cause
Disease-free survival (DFS) rates	Up to approximately 2 years	Disease-free survival (DFS) rates was defined as the time from the date of first study treatment to the time of the subject's first high-grade Ta, T1 of any grade, CIS lasting greater than or equal to 6 months, new carcinoma in situ (CIS), cystectomy, disease progression, or death from any cause

Trial Locations

Locations (6)

Hunan Cancer hospital; 🇨🇳 Changsha, Hunan, China

Tongji Hospital; 🇨🇳 Wuhan, Hubei, China

West China Hospital; 🇨🇳 Chengdu, Sichuan, China

The first affiliated hospital with nanjing medical universtity; 🇨🇳 Nanjing, Jiangsu, China

Sun Yat-sen Memorial Hospital,SunYat-sen University; 🇨🇳 Guangzhou, Guangdong, China

Tianjin Medical University Second Hospital; 🇨🇳 Tianjin, Tianjin, China