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
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- RemeGen Co., Ltd.
- Enrollment
- 24
- Locations
- 6
- Primary Endpoint
- Incidence of Adverse event (Phase I)
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Voluntary consent to participate in the study and signed the informed consent form.
- •Male or female, age 18-75 years (including both).
- •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.
- •Absence of resectable disease（Ta and/or T1 disease） after transurethral resection (TURBT) procedures (residual CIS acceptable;
- •The urologist assessed that radical surgery for bladder cancer was not suitable or the subject refused radical surgery for bladder cancer.
- •Tumor tissue samples were detected by immunohistochemistry (IHC) to satisfy HER2 expression of 1+, 2+ or 3+.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Adequate heart, bone marrow, liver, kidney and coagulation function
Exclusion Criteria
- •Invasive bladder cancer (T2 and above) and / or with regional lymph node and distant metastasis.
- •Combined urothelial carcinoma outside the bladder (i. e., urethra, ureter or renal pelvis).
- •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.
Arms & Interventions
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.
Intervention: Disitamab Vedotin for injection (Drug)
Outcomes
Primary Outcomes
Incidence of Adverse event (Phase I)
Time Frame: 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)
Time Frame: Approximately 21 days
Assessed based on the Incidence of DLT
Incidence of dose-limiting toxicity(DLT) (Phase I)
Time Frame: Approximately 21 days
Maximum Tolerated Dosage(MTD)
Time Frame: Approximately 21 days
Assessed based on the Incidence of DLT
Secondary Outcomes
- Disitamab Vedotin anti-drug antibody (ADA)(Up to approximately 2 years)
- PK of enfortumab vedotin: Maximum concentration (Cmax)(Approximately 1 years)
- PK of enfortumab vedotin: Trough concentration (Ctrough)(Approximately 1 year)
- Duration of response (DOR)(Up to approximately 2 years)
- Disease-free survival (DFS) rates(Up to approximately 2 years)