Probiotics Combined With Targeted Therapy Plus Immunotherapy in Bladder-Preserving Setting for Patients With MIBC

A Multicenter Randomized Controlled Study to Evaluate the Efficacy of Oral Probiotics Combined With PD-1 Monoclonal Antibody and Disitamab Vedotin in Bladder-Preserving Setting for Cisplatin-Ineligible Patients With Muscle-Invasive Bladder Cancer and Low Serum Butyrate

The goal of this clinical trial is to learn if oral probiotics (Clostridium butyricum) work to improve the efficacy of targeted therapy plus immunotherapy in bladder preservation setting for cisplatin-ineligible T2-3N0M0 bladder cancer patients with low serum butyrate.

The main questions it aims to answer are: Do oral probiotics elevate serum butyrate levels and enhance the duation of bladder preservation interval with targeted therapy plus immunotherapy? Researchers will compare oral probiotics combined with targeted therapy plus immunotherapy to standard regimens (targeted therapy plus immunotherapy) to see if oral probiotics can improve its efficacy.

Participants will:

1. Take oral probiotics and/or Disitamab Vedotin (HER2-ADC) and Toripalimab (PD-L1 inhibitor) for one year in total, which is divided into induction treatment period, intensive treatment period and maintenance treatment period.
2. Return to the hospital for evaluation of tumor residual burden according to the follow-up plan, which will include urine cytology, imaging, surgical biopsy, and urine DNA methylation detection.

Study Overview

• Status: Not yet recruiting
• Conditions: Muscle Invasive Bladder Cancer (MIBC)
• Intervention / Treatment: Drug: Probiotic; Drug: Disitamab Vedotin; Drug: Toripalimab

• Study Type: Interventional
• Enrollment (Estimated): 146
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Junlin Lu, MD; Phone Number: +86-020-81332199; Email: lujlin7@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Sun Yat-Sen Memorial Hospital
      • Contact: Li Yan; Phone Number: +86-020-81332587; Email: sysyxllwyh@163.com
      • Principal Investigator: Xu Chen, PhD, MD
      • Principal Investigator: Tianxin Lin, PhD, MD
      • Sub-Investigator: Junlin Lu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients have histologically confirmed, radiologically staged cT2-3N0M0 urothelial carcinoma of the bladder, in which urothelial carcinoma is the predominant component (>50%).
• Serum butyrate level <46 μg/L as determined by quantitative mass spectrometry.
• HER2 expression is assessed by immunohistochemistry (IHC) on pretreatment tumor specimens, with confirmed IHC ≥1+.
• Patients are deemed ineligible for radical cystectomy based on laboratory evaluation and patient preference.
• Patients considered ineligible for cisplatin therapy and meeting at least one of the following criteria: ECOG performance status >1 or Karnofsky performance status of 60-70%; Creatinine clearance <60 mL/min; Hearing loss ≥ Grade 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0; Peripheral neuropathy ≥ Grade 2 (NCI-CTCAE v5.0); New York Heart Association (NYHA) Class III or higher heart failure.
• ECOG performance status of 0-2.
• Adequate cardiac, bone marrow, hepatic, renal, and coagulation functions.

Exclusion Criteria:

• Prior ADCs or PD-1/PD-L1 inhibitor therapy.
• Known hypersensitivity to microbiota-related preparations (microecological products), RC48-ADC or Toripalimab or any of its components.
• Receipt of other approved systemic anticancer therapy or systemic immunomodulatory agents (including but not limited to interferon, interleukin-2, and tumour necrosis factor) within 28 days prior to enrolment.
• Prior radiotherapy for bladder cancer.
• Prior antitumour drug therapy, except for the following: a. For patients who previously received systemic chemotherapy, a treatment-free interval of at least 3 months between the last dose and the start of induction therapy is required; b. Local intravesical chemotherapy or immunotherapy (including BCG) must be completed at least 1 week before initiation of study neoadjuvant treatment.
• Surgery or significant trauma within 28 days prior to enrolment (implantation of vascular access devices and TURBT are not considered).
• Severe chronic or active infection requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to enrolment.
• Receipt of live vaccines within 28 days prior to enrolment.
• Active autoimmune disease requiring systemic treatment and considered by the investigator to potentially interfere with the study treatment.
• Requirement for long-term high-dose corticosteroids or other immunosuppressive agents.
• Clinically significant abnormalities that may affect treatment, including electrolyte disturbances, hypoalbuminaemia, interstitial lung disease, non-infectious pneumonitis, or other uncontrolled systemic diseases. These include uncontrolled diabetes, hypertension, or cardiovascular disease, such as active cardiac conditions within 6 months prior to enrolment.
• Untreated chronic hepatitis B with HBV DNA ≥500 IU/mL (2,500 copies/mL) or known HBV carriers with active disease.
• Active hepatitis C infection.
• History of immunodeficiency, including positive human immunodeficiency virus (HIV) test, other acquired or congenital immunodeficiency disorders, or a history of allogeneic stem cell transplantation or solid organ transplantation.
• Toxicities from prior therapies that have not recovered to baseline or stabilised.
• Presence of other concomitant malignancies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic + Disitamab Vedotin + Toripalimab; Participants will receive oral Clostridium butyricum viable tablets, disitamab vedotin, and toripalimab for about 1 year, or until investigator-assessed bladder preservation failure, loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).	Drug: Probiotic; 80 mg orally twice daily during induction and intensive treatment periods; 80 mg orally twice daily, 3 weeks on / 3 weeks off dosing schedule during maintenance treatment period; Other Names: Clostridium butyricum CBM 588 Probiotic Strain; Drug: Disitamab Vedotin; 2.0 mg/kg IV every 2 weeks during the induction treatment period and intensive treatment period; Other Names: RC48-ADC; Drug: Toripalimab; 3.0 mg/kg IV every 2 weeks during the induction and intensive treatment periods; followed by 240 mg IV every 3 weeks during the maintenance treatment period.; Other Names: JS001
Active Comparator: Disitamab Vedotin + Toripalimab; Participants will receive disitamab vedotin and toripalimab for about 1 year, or until investigator-assessed bladder preservation failure, loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).	Drug: Disitamab Vedotin; 2.0 mg/kg IV every 2 weeks during the induction treatment period and intensive treatment period; Other Names: RC48-ADC; Drug: Toripalimab; 3.0 mg/kg IV every 2 weeks during the induction and intensive treatment periods; followed by 240 mg IV every 3 weeks during the maintenance treatment period.; Other Names: JS001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
bladder-intact event free survival (BI-EFS), evaluated by independent review committee	Bladder intact event-free survival (BIEFS) refers to the time from the date of randomization to the first occurrence of any bladder preservation failure event through tumor control, whichever occurs first. Bladder preservation failure events include: 1. Rapid progression: progressive disease (PD) assessed by imaging at the mid-induction evaluation; 2. Tumor recurrence: ≥T2 stage, high-grade urothelial carcinoma (per the WHO 2016 Classification of Tumours of the Urinary System), or non-urothelial carcinoma histology; 3. Tumor metastasis: including lymph node metastasis and distant organ metastasis; 4. Death from any cause; 5. Receipt of radical cystectomy for any other reason.	Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Overall survival (OS) refers to the time from the date of randomization to the date of death of the subject.	Up to approximately 3 years
clinical complete response (cCR)	Clinical complete response rate (cCR) refers to the proportion of participants who achieve all of the following criteria after completion of induction treatment: first, negative urine cytology; second, no new lymph node metastasis or distant metastatic lesions identified on imaging examinations; third, no malignant tumor identified on cystoscopy biopsy, or only low-grade Ta/T1 urothelial carcinoma present.	Up to approximately 3 years
Metastasis-free survival (MFS)	Metastasis-free survival (MFS) refers to the time from the date of randomization to the first occurrence of lymph node metastasis or distant organ metastasis, whichever occurs first.	Up to approximately 3 years

Collaborators and Investigators

• Sponsor: chenxu

Study record dates

Study Major Dates

• Study Start (Estimated): March 26, 2026
• Primary Completion (Estimated): March 31, 2031
• Study Completion (Estimated): March 31, 2035

Study Registration Dates

• First Submitted: March 10, 2026
• First Submitted That Met QC Criteria: March 10, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 15, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; disitamab vedotin; Probiotics; toripalimab
• Other Study ID Numbers: PTI-BPS-2026-IIT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) will be made available to qualified researchers, along with the study protocol and statistical analysis plan (SAP), after the publication of primary study results. Requests will be reviewed by the study sponsor and steering committee. Data will be shared via a secure, password-protected research data repository for non-commercial, scientific purposes only, in compliance with applicable regulations and ethical approvals.
• IPD Sharing Time Frame: IPD will be available starting 6 months after the publication of the primary study results, and will remain accessible for a period of 5 years thereafter.
• IPD Sharing Access Criteria: Access will be granted to qualified independent researchers with a scientifically sound research proposal focused on non-commercial objectives.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No