RC48 Combined With Toripalimab as Neoadjuvant Therapy for Cisplatin Ineligible MIBC Patients

Prior treatment

• toxicity from previous antineoplastic therapy did not revert to CTCAE grade 0-1 (except grade 2 alopecia).
• received live virus vaccine within 4 weeks after planned initiation of trial treatment.
• receiving systemic therapy (e.g., immunomodulatory agents, corticosteroids, or immunosuppressive agents) for autoimmune disease within 2 years before study treatment.

Other illness

• known hypersensitivity to components of recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate or allergic reaction to toripalimab.
• history of major surgery within 4 weeks of planned initiation of trial treatment.
• currently known active HIV or tuberculosis infection.
• diagnosed as HBsAg, HBcAb positive and HBV DNA copy positive, or HCVAb positive.
• history of other malignancies within the past 5 years.
• uncontrolled hypertension, diabetes, interstitial lung disease, or chronic obstructive pulmonary disease.
• NYHA class III heart failure.

Lab values

• there is history or current evidence of any condition, treatment, or laboratory abnormality that the treatment investigator believes may confound the trial results, interfere with the participant's participation throughout the trial, or be inconsistent with the participant's participation.

Other

• pleural or abdominal effusion with clinical symptoms requiring ongoing treatment.
• known central nervous system metastases
• pregnancy or lactation.
• were assessed by the investigator as unable or unwilling to comply with the requirements of the protocol.

• Voluntarily agree to provide written informed consent.
• Male or female, aged ≥18 years old.
• Patients must be ineligible for cisplatin-based chemotherapy or refuse cisplatin-based chemotherapy because of any of the following:
  • Creatinine clearance (CrCl) \<60 mL/min, ECOG performance status (PS) 0-1 Creatinine clearance (CrCl) ≥ 60 mL/min, ECOG PS 2 (if the patient is eligible for RC) Hearing impairment ≥ CTCAE level 2 According to CTCAE criteria, neuropathy was ≥ grade 2 The patient declined cisplatin-based chemotherapy
• Patients must be medically suitable for TURBT and RC.
• Pathological examination and immunohistochemical Her-2 (≥1+)
• measurable lesions according to RECIST 1.1.
• Adequate organ function, as demonstrated by the following laboratory results within 7 days before study treatment:
  • The heart ejection fraction was ≥50%. Hemoglobin ≥9 g/dL; Absolute neutrophil count ≥ 1.5×109 /L and platelet ≥ 100×109 /L; Total bilirubin ≤ 1.5× ULN; AST and ALT ≤ 2.5×ULN and ≤ 5×ULN.
• All female subjects will be considered to be of reproductive potential unless they are postmenopausal or have been surgically sterilized. Female subjects of childbearing potential had to consent to the use of highly effective contraception. Male subjects of childbearing potential and their female partners had to consent to the use of highly effective contraception.
• Be willing to comply with the study access schedule and the prohibitions and restrictions set forth in this Agreement.