A Study to Evaluate the Efficacy and Safety of Intravesical Instillation of Disitamab Vedotin Combined With Toripalimab in Patients With HER2-Positive High-Risk Non-Muscle Invasive Bladder Cancer Who Are BCG-Naïve or Have BCG Failure

NCT07783815 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: Xiangya202604051
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open-label, single-arm investigator-initiated clinical trial, aiming to evaluate the efficacy and safety of vicedetinib bladder instillation combined with teprotumumab in the treatment of patients with HER2-expressing, previously untreated, or BCG-resistant high-risk non-muscle-invasive bladder cancer (NMIBC). The subjects to be included in the study must have undergone standard TURBT within 3 weeks before enrollment, removed all visible lesions, and had a clear pathological diagnosis of NMIBC, with their risk classification according to the "Chinese Bladder Cancer Diagnosis and Treatment Guidelines (2022)" falling into the high-risk group (including extremely high-risk group). All surgical tumor specimens of the included subjects underwent HER2 testing, indicating HER2 expression, defined as immunohistochemistry (IHC) 1+, 2+ or 3+, with FISH verification for amplification if IHC 2+ is present. The subjects were divided into two groups based on whether they had received BCG treatment in the past: one group was high-risk NMIBC patients who had not received BCG treatment, including one of the following situations: ① refused BCG treatment, ② had contraindications to BCG use, ③ BCG was inaccessible; the other group was high-risk NMIBC patients who had no response to BCG, meeting any of the following criteria: ① had persistent/recurrent high-risk NMIBC within 12 months (±1 month) after adequate BCG treatment, ② had high-grade T1 disease during the first assessment after induction BCG treatment. Adequate BCG treatment was defined as completing at least 5 BCG bladder instillations within 2 months, and then at least 2 BCG bladder instillations for 6 consecutive weeks within the next 10 months, meaning at least "5+2" BCG bladder instillations within approximately 12 months. Eligible subjects received vicedetinib bladder instillation combined with teprotumumab treatment; vicedetinib was administered once weekly at 180mg for 8 times. For patients receiving treatment, if there was no occurrence of persistent/recurrent NMIBC, disease progression, or intolerable toxicity, they would receive maintenance bladder instillation with vicedetinib for one year, with the maintenance regimen being: once every 4 weeks for 10 times. Teprotumumab: 240mg per dose, intravenous, once every 3 weeks for 1 year. Patients were required to collect urine samples before the first treatment and after the last treatment. Safety during the study was evaluated according to the NCI-CTCAE V5.0 standard, and the observation indicators included vital signs, physical examination, laboratory tests, electrocardiogram and echocardiogram examinations, adverse events and serious adverse events.

Conditions

Bladder Cancer

Keywords

High-risk non-muscle-invasive bladder cancer; Disitamab Vedotin; Toripalimab; Bladder instillation; HER2

Outcome Measures

Primary Outcomes (1)

• The one-year recurrence-free survival rate of patients with high-risk NMIBC

  After all subjects have been enrolled and followed up for an additional 12 months, or upon achievement of the required number of positive events, Recurrence-Free Survival (RFS) will be analyzed using the Kaplan-Meier method. The median recurrence-free time will be estimated via the Kaplan-Meier method. Hazard ratios (HR) and their 95% confidence intervals will be calculated using the Cox proportional hazards model.

  One year after the treatment

Secondary Outcomes (4)

• The clinical complete remission rates for 3 months and 6 months

  Three months and six months after the treatment

• Overall survival period

  through study completion, an average of 3 years

• Progression-free survival time

  through study completion, an average of 3 years

• Adverse event

  through study completion, an average of 3 years

Study Arms (1)

Intravesical Instillation of Disitamab Vedotin Combined with Toripalimab

EXPERIMENTAL

Eligible subjects will be enrolled and treated with intravesical instillation of disitamab vedotin combined with toripalimab. Disitamab vedotin will be administered at a dose of 180 mg once weekly for 8 consecutive cycles. For treated patients without persistent/recurrent NMIBC, disease progression, or intolerable toxicity, maintenance intravesical instillation of disitamab vedotin will be performed within 1 year. The regimen for maintenance therapy is 180 mg once every 4 weeks for 10 consecutive cycles. Toripalimab will be administered intravenously at a dose of 240 mg once every 3 weeks for 1 consecutive year.

Drug: Intravesical Instillation of Disitamab Vedotin Combined with Toripalimab

Interventions

Intravesical Instillation of Disitamab Vedotin Combined with Toripalimab DRUG

Eligible subjects will be enrolled and treated with intravesical instillation of disitamab vedotin combined with toripalimab. Disitamab vedotin will be administered at a dose of 180 mg once weekly for 8 consecutive cycles. For treated patients without persistent/recurrent NMIBC, disease progression, or intolerable toxicity, maintenance intravesical instillation of disitamab vedotin will be performed within 1 year. The regimen for maintenance therapy is 180 mg once every 4 weeks for 10 consecutive cycles. Toripalimab will be administered intravenously at a dose of 240 mg once every 3 weeks for 1 consecutive year.

Intravesical Instillation of Disitamab Vedotin Combined with Toripalimab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily agree to participate in the research and sign the informed consent form.
• Within 3 weeks after TURBT surgery, the tumor tissue specimens obtained from the subjects were subjected to immunohistochemical (IHC) testing for HER2 expression, which met the criteria of 1+, 2+ or 3+. If the IHC result was 2+, FISH verification for amplification was required.
• ECOG physical condition: 0 - 2 points.
• Sufficient heart, bone marrow, liver and kidney functions should meet the following standards within 7 days before the drug administration study (normal values are based on the clinical trial center): Left ventricular ejection fraction ≥ 50%; Hemoglobin ≥ 9 g/dL; Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L; Platelets ≥ 100 × 10\^9/L; Serum total bilirubin ≤ 1.5 times the upper limit of normal value (ULN); ALT and AST ≤ 2.5 × ULN; Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance rate (CrCl) ≥ 50 mL/min according to the Cockcroft-Gault formula.
• Within 3 weeks after TURBT surgery, the tumor tissue specimens obtained from the subjects were subjected to immunohistochemical (IHC) testing for HER2 expression, which met the criteria of 1+, 2+ or 3+. If the IHC result was 2+, FISH verification for amplification was required.
• ECOG physical condition: 0 - 2 points.
• Sufficient heart, bone marrow, liver and kidney functions should meet the following standards within 7 days before the drug administration study (normal values are based on the clinical trial center): Left ventricular ejection fraction ≥ 50%; Hemoglobin ≥ 9 g/dL; Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L; Platelets ≥ 100 × 10\^9/L; Serum total bilirubin ≤ 1.5 times the upper limit of normal value (ULN); ALT and AST ≤ 2.5 × ULN; Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance rate (CrCl) ≥ 50 mL/min according to the Cockcroft-Gault formula.
• The female subjects should be patients who have undergone surgical sterilization or menopause, or those who agree to use at least one medically approved contraceptive method (such as intrauterine device, contraceptive pills or condoms) during the study treatment period and within 6 months after the end of the study treatment. The blood pregnancy test must be negative within 7 days before the subject is enrolled in the study. False positive results can be excluded after confirming pregnancy by the investigator and then the subject can be enrolled. Male subjects should agree to use at least one medically approved contraceptive method during the study treatment period and within 6 months after the end of the study treatment.
• Willing and able to comply with the arrangements of the trial and follow-up procedures.
• Willing and able to comply with the arrangements of the trial and follow-up procedures.

You may not qualify if:

• Muscle-invasive bladder cancer (T2 and above) and/or those with regional lymph node and distant metastasis.
• Combined urinary tract urothelial carcinoma outside the bladder (i.e., in the urethra, ureters or renal pelvis).
• Before the start of the drug study, there was no recovery from the adverse events caused by the previously used anti-tumor drugs to the 0-1 level of CECAT within 2 weeks.
• Those who started the drug administration within 4 weeks before the study or those who planned to undergo major surgery during the trial period.
• Serological virological examination (based on the normal values of the research center): HBsAg or HBcAb test results are positive, and HBVDNA copy number is also positive; HCVAb test result is positive, and HCV RNA test result is also positive; HIVAb test result is positive.
• The study excluded participants who had received live vaccines within 4 weeks prior to the start of the treatment or who planned to receive any vaccines during the study period (except for the novel coronavirus inactivated virus vaccine).
• Heart failure classified as grade 3 or above by the New York Heart Association (NYHA) in the United States.
• The study excluded cases where there had been severe arterial/venous thrombosis events or cardiovascular/cerebrovascular accidents within 6 months before administration, such as deep vein thrombosis, pulmonary embolism, cerebral infarction, cerebral hemorrhage, myocardial infarction, etc. However, cases of asymptomatic and non-requirement-of-clinical-intervention lacunar cerebral infarction were included.
• There are active or progressive infections that require systematic treatment, such as active tuberculosis.
• There are systemic diseases that have been judged by the researchers to be active and not yet under stable control, as well as severe comorbidities, including diabetes, hypertension, liver cirrhosis, interstitial pneumonia, obstructive pulmonary disease, etc.
• Previous history of receiving allogeneic hematopoietic stem cell transplantation or organ transplantation.
• Those who are known to be allergic to RC48-ADC/Teripipor or any of its components or any of the excipients.
• Pregnant or lactating women.
• It is estimated that the patient's compliance with this clinical study is insufficient.

Sponsors & Collaborators

• Xiangya Hospital of Central South University: lead

Study Sites (1)

Xiangya Hospital

Changsha, Hunan, China

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

toripalimab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Central Study Contacts

Huihuang Li, Doctor of Medicine

CONTACT

+86-731-8975-3011; lhhuang1994@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2026
• First Posted: August 25, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): February 1, 2030
• Last Updated: August 25, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)