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

NCT07142200 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: IIT-2024-0409
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

muscle-invasive bladder cancer; Disitamab Vedotin; PD-1 Inhibitor; Radiotherapy; Bladder-preserving Therapy

Outcome Measures

Primary Outcomes (1)

• 3-month Complete Response (3-month CR)

  Three months after the start of treatment, if there is no visible tumor detected by imaging examination, the pathological evaluation of the tumor site obtained by diagnostic TURBT/cystoscopy is negative, and the urine cytology(for example, urine TCT) is negative, it is defined as CR. For the primary efficacy endpoint CR, the exact binomial distribution method will be used to provide point estimates, 95% confidence intervals, and p-values for testing response rates higher than the historical control (20%).

  3 months

Secondary Outcomes (7)

• 6/12/24-month Complete Response (6/12/24-month CR)

  6/12/24 months

• Bladder Intact Event-Free Survival (BI-EFS)

  2 years

• Relapse-Free Survival (RFS)

  2 years

• Cancer-Specific Survival (CSS)

  2 years

• Overall Survival (OS)

  2 years

Study Arms (1)

Single Arm

EXPERIMENTAL

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. The subjects need to undergo maximum transurethral resection of the bladder (TURBT) and imaging diagnosis, and collect urine samples before treatment. 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 and the overall condition. Patients with safety intolerance caused by any drug treatment will be reduced or discontinued according to the dosage adjustment plan specified in the protocol.

Drug: Disitamab Vedotin; Drug: PD-1 inhibitor; Radiation: radiotherapy

Interventions

Disitamab Vedotin DRUG

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.

Single Arm

PD-1 inhibitor DRUG

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.

Single Arm

radiotherapy RADIATION

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

Single Arm

Eligibility Criteria

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

You may qualify if:

• Men or women aged ≥ 18 years old;
• ECOG PS:0～1;
• The subjects need to undergo maximum TURBT surgery (no need for secondary resection) and imaging diagnosis. The researchers have determined that MIBC (urothelial carcinoma as the main pathological component\>50%) is present, and plan to undergo radical cystectomy, lymph node dissection, and urinary diversion surgery;
• cT2-T4a N0 M0 （CT/MRI ± PET/CT）;
• Accept maximum TURBT;
• Have tissue examination specimens with TURBT;
• Expected survival period ≥ 3 months;
• The immunohistochemical staining result of the tissue after the last TURBT surgery was IHC 2+or 3+;
• The main organ function is normal (14 days before enrollment), which meets the following criteria:
• The standard for blood routine examination must meet the following criteria: (no blood transfusion or treatment with granulocyte colony-stimulating factor within 14 days before enrollment):
• HB≥90 g/L； ANC≥1.5×109 /L； PLT≥100×109 /L；
• Non functional organic diseases must meet the following criteria:
• T-BIL ≤ 1.5 × ULN (upper limit of normal value); ALT and AST ≤ 2.5 × ULN; If there is liver metastasis, ALT and AST should be ≤ 5 × ULN; Blood creatinine ≤ 1.5 × ULN or creatinine clearance rate (CrCl) calculated according to the Cockcroft Gault formula ≥ 50 mL/min; International normalized ratio (INR) and activated partial thromboplastin time (aPTT): ≤ 1.5 × ULN (this standard is only applicable to patients who have not received anticoagulant therapy); Patients receiving anticoagulant therapy should ensure that the anticoagulant is within the required treatment range;
• Have not received systemic corticosteroid treatment within 4 weeks prior to treatment;
• Men with reproductive ability or women with the possibility of pregnancy must use highly effective contraceptive methods during the trial (such as oral contraceptives, intrauterine devices, abstinence control or barrier contraception combined with spermicides), and continue contraception for 12 months after the end of treatment;

You may not qualify if:

• Previous treatment with anti-PD-1, anti-PD-L1, and anti-PD-L2, including adjuvant therapy phase;
• Individuals known to be allergic to recombinant humanized anti-PD-1 monoclonal antibody drugs and their components;
• Those who have received systemic chemotherapy, radiation therapy, or other anti-tumor treatments (including corticosteroid therapy, immunotherapy) or participated in other clinical studies within 4 weeks before the start of treatment, or have not yet recovered from the previous toxicity (excluding 2nd degree hair loss and 1st degree neurotoxicity);
• Pregnant or lactating women;
• Positive HIV test result;
• Active hepatitis B or C patients HBsAg or HBcAb positive individuals were simultaneously detected with HBV DNA copy number positivity (quantitative detection limit is 500IU/ml, or reaching the copy number positivity value detected by the research center); Patients of this type must undergo HBV DNA testing during screening studies; Patients with positive HCV antibody test results are only eligible for this study if their HCV RNA PCR test results are negative;
• Have a clear history of active tuberculosis;
• Active autoimmune diseases that require systematic treatment within the past 2 years (such as the use of disease regulating drugs, corticosteroids, or immunosuppressive drugs), allowing for related alternative treatments (such as thyroid hormone, insulin, or physiological corticosteroid replacement therapy for renal or pituitary dysfunction);
• Other serious and uncontrollable concomitant diseases that may affect the compliance of the scheme or interfere with the interpretation of the results, including active opportunistic infections or progressive (serious) infections, uncontrollable diabetes, cardiovascular diseases (Grade III or IV heart failure defined by the New York Heart Association classification, Grade II or above heart block, myocardial infarction, unstable arrhythmia or unstable angina pectoris in the past six months, cerebral infarction in three months, etc.) or lung diseases (interstitial pneumonia, obstructive pulmonary disease, and symptomatic bronchospasm history);
• Previously received live vaccination within 4 weeks before the start of treatment;
• Previously received allogeneic hematopoietic stem cell transplantation or solid organ transplantation;
• Significant surgical procedures (excluding diagnostic surgeries or TURBT) performed within the 4 weeks prior to the start of treatment;
• Individuals with a history of substance abuse and inability to quit, or those with a history of mental disorders;
• Large amounts of pleural or ascites accompanied by clinical symptoms or requiring symptomatic treatment;
• In the past 5 years, have had other malignant tumors that have not been cured, but do not include malignant tumors that have been clearly cured, or curable cancers such as basal or squamous cell carcinoma, localized low-risk prostate cancer, cervical in situ cancer, or breast in situ cancer; Note: Localized low-risk prostate cancer (defined as patients with stage ≤ T2b, Gleason score ≤ 7, and PSA ≤ 20ng/mL (as measured) at the time of prostate cancer diagnosis who have received curative treatment and have no biochemical recurrence of prostate-specific antigen (PSA) may participate in this study);

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Renji Hospital, Shanghai Jiaotong University School of Medecine

Shanghai, Shanghai Municipality, 200127, China

Location

MeSH Terms

Conditions

Neoplasms

Interventions

disitamab vedotin; Immune Checkpoint Inhibitors; Radiotherapy

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Therapeutics

Central Study Contacts

Haige Chen, bachelor

CONTACT

+8619858372866; 2903654937@qq.com

Ruiyun Zhang, Doctor

CONTACT

+8615202138366; 2903654937@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2025
• First Posted: August 26, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 26, 2025

Record last verified: 2025-08

Locations

CN (1)