A Clinical Study Evaluating the Efficacy and Safety of Disitamab Vedotin Combined With PD-1 Inhibitor and Radiotherapy as Bladder-preserving Therapy in Patients With Localized HER2-high Expressing Muscle-invasive Bladder Urothelial Carcinoma Following Maximal Transurethral Resection

Summary

This is a prospective, open label, multicenter clinical study of vediximab combined with PD-1 and radiation therapy for bladder preservation in MIBC patients with HER-2 high expression (IHC 2+or 3+), conducted in accordance with Good Clinical Practice (GCP).

Each patient received treatment with Vediximab injection \[2.0 mg/kg, Q2W, iv\] and Triprolizumab injection \[3mg/kg, Q2W, iv\] for one cycle, followed by concurrent radiotherapy in the second cycle. Assuming a 20% improvement in the efficacy of conventional TMT bladder protection treatment, i.e. an increase in CR rate from 60% to 80%, alpha of 0.05, and beta of 0.2, a sample size of 36 is required. Considering a 20% dropout rate, 45 subjects need to be enrolled.

The subjects need to undergo maximum transurethral resection of the bladder (TURBT) and imaging diagnosis, and collect urine samples before treatment. The researchers judged that localized myometrial invasive bladder cancer with high HER2 expression could be treated with bladder conserving therapy by maximizing TURBT. The patient will receive treatment with vediximab combined with PD-1 and radiotherapy after TURBT surgery (without the need for secondary resection).

The subjects should receive treatment with vediximab combined with PD-1 every two weeks for a total of 12 treatment cycles, and receive radiation therapy simultaneously. The specific number of treatment cycles will be determined by the researchers based on the patient's response to the treatment, tolerance to the regimen, and overall judgment of the condition. Patients with safety intolerance caused by any drug treatment will be reduced or discontinued according to the dosage adjustment plan specified in the regimen.

After completing the above treatments, the pathology, imaging, and cytology of the tumor site were obtained through diagnostic TURBT or cystoscopy for tumor evaluation to assess whether complete remission was achieved. The first tumor efficacy evaluation was conducted 3 months after receiving treatment, and the researcher judged whether to continue treatment based on the patient's treatment status. After completing the treatment for the next 3 months, another tumor efficacy evaluation was conducted. After completing all 12 treatment cycles (6 months), the patient underwent two tumor evaluations at the 6th month (from the 12th month of treatment) and the 12th month (from the 24th month of treatment), respectively.

Conditions

• Bladder (Urothelial, Transitional Cell) Cancer

Interventions

DRUG

Disitamab Vedotin

Each patient will receive Disitamab Vedotin injection \[2.0 mg/kg, Q2W, iv\], with an expected total of 12 courses of treatment. The specific number of treatment cycles is determined by researchers based on the patient's response to the treatment, tolerance to the treatment plan, and comprehensive assessment of the condition. Patients with safety intolerance caused by any drug treatment should reduce or discontinue the medication according to the dosage adjustment plan specified in the plan. The medication is diluted with physiological saline and administered intravenously for one hour.

DRUG

PD-1 inhibitor

Each patient will receive Triprolizumab injection \[3mg/kg, Q2W, iv\], with an expected total of 12 courses of treatment. The specific number of treatment cycles is determined by researchers based on the patient's response to the treatment, tolerance to the treatment plan, and comprehensive assessment of the condition. Patients with safety intolerance caused by any drug treatment should reduce or discontinue the medication according to the dosage adjustment plan specified in the plan. The medication is diluted with physiological saline and administered intravenously for one hour.

RADIATION

radiotherapy

1. Whole bladder treatment, recommended scope of application: T2 Suggestion: The total bladder radiotherapy dose is 2Gy/day, five times a week, up to a dose of 50Gy/25 times, to cover at least 95% of the planned target volume (PTV full bladder). The radiation dose for shrinking the field to bladder tumors is 2Gy/day, five times a week, with a total dose of 14Gy/7 times, to cover at least 95% of the planned target dose (PTV bladder tumors). 2. Whole pelvic radiotherapy (whole bladder+selective pelvic lymph node radiotherapy), applicable range: T3-T4a Suggestion: Whole pelvic radiotherapy at 2Gy/day, five times a week, up to a dose of 46Gy/23 times, to cover at least 95% of the planned target dose. Reduce the dosage to 2Gy/day for the entire bladder and up to 4Gy/twice. Bladder tumor (PTV bladder tumor) 2Gy/day, five times a week, with a total dose of 14Gy/7 times, to cover at least 95% of the planned target volume. The above radiotherapy plan is a suggestion, and the specific plan will

Sponsors & Collaborators

• RenJi Hospital

  lead OTHER

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-09-01

Primary Completion

2026-06-30

Completion

2027-12-31

Countries

• China

Study Locations