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

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

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

Study Overview

• Status: Recruiting
• Conditions: High-risk Non-muscle Invasive Bladder Cancer
• Intervention / Treatment: Drug: Disitamab Vedotin for injection

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 Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Hong Luo; Phone Number: +8610-58075763; Email: hong.luo@remegen.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Sun Yat-sen Memorial Hospital,SunYat-sen University
      • Contact: Tianxin Lin, Ph.D
  • Hubei
    • Wuhan, Hubei, China
      • Not yet recruiting
      • Tongji Hospital
      • Contact: Shaogang Wang, M.D
  • Hunan
    • Changsha, Hunan, China
      • Recruiting
      • Hunan Cancer Hospital
      • Contact: Shusuan Jiang, M.D
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Not yet recruiting
      • The first affiliated hospital with nanjing medical universtity
      • Contact: qiang Lv, M.D
  • Sichuan
    • Chengdu, Sichuan, China
      • Not yet recruiting
      • West China Hospital
      • Contact: Peng Zhang, M.D
  • Tianjin
    • Tianjin, Tianjin, China
      • Not yet recruiting
      • Tianjin Medical University Second Hospital
      • Contact: Hailong Hu, M.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Disitamab Vedotin Intravesical instiliations :Dose escalation cohort; Participants will receive Disitamab Vedotin for injection Intravesical instiliations into the bladder for 1 hour, D1, once a week.	Drug: Disitamab Vedotin for injection; Intravesical instiliations into the bladder; Other Names: RC48

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK of enfortumab vedotin: Trough concentration (Ctrough)	Ctrough will be recorded from the PK blood samples collected.	Approximately 1 year
Disease-free survival (DFS) rates	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	Up to approximately 2 years
Duration of response (DOR)	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	Up to approximately 2 years
Disitamab Vedotin anti-drug antibody (ADA)	The number and proportion of anti-drug antibody (ADA)-positive subjects were analyzed according to dose group and time point.	Up to approximately 2 years
PK of enfortumab vedotin: Maximum concentration (Cmax)	Cmax will be recorded from the PK blood samples collected.	Approximately 1 years

Collaborators and Investigators

• Sponsor: RemeGen Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2024
• Primary Completion (Estimated): March 15, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: April 12, 2024
• First Submitted That Met QC Criteria: April 19, 2024
• First Posted (Actual): April 22, 2024

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: July 9, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: HER2-expression; High-risk non-muscle invasive bladder cancer; intravesical instiliations
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Immunoconjugates; Disitamab vedotin
• Other Study ID Numbers: RC48-C029

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No