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

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.