High-risk Non-muscle Invasive Bladder Cancer
Conditions
Keywords
HER2-expression, High-risk non-muscle invasive bladder cancer, intravesical instiliations
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.
Interventions
Intravesical instiliations into the bladder
Sponsors
RemeGen Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose-limiting toxicity(DLT) (Phase I) | Approximately 21 days | — |
| 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 |
| Maximum Tolerated Dosage(MTD) | Approximately 21 days | Assessed based on the Incidence of DLT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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 |
| 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. |
Countries
China
Contacts
Primary ContactHong Luo
Outcome results
None listed