A Study of RC48-ADC Combined With Cadonilimab（AK104）in the Treatment of HER2-expression Locally Advanced or Metastatic Urothelial Carcinoma

An Open-label, Single-arm, Multi-center, Phase II Study to Evaluate the Efficacy and Safety of RC48-ADC Combined With AK104 in HER2-expression Locally Advanced or Metastatic Urothelial Carcinoma

This study will evaluate the efficacy and safety of RC48-ADC combined with AK104 in HER2-expression locally advanced or metastatic urothelial carcinoma.

Inclusion Criteria:

• Voluntary agreement to provide written informed consent.
• Male or female, Age ≥ 18 years.
• Predicted survival ≥ 6 month.
• Histologically and/or cytologically confirmed locally advanced or metastatic urothelial carcinoma (including urothelial carcinoma originating in the renal pelvis, ureter, bladder, or urethra).
• Pior not received systemic therapy, and can not tolerant cisplatin or refuse chemotherapy.
• HER2 expressing (i.e. IHC 1+ 2+ or 3+) as confirmed by the local lab.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Have at least one evaluable lesion (RECIST 1.1 criteria)
• Adequate organ function, evidenced by the following laboratory results within 7 days prior to the study treatment.
• Male and female participants are eligible to participate if they agree to the contraception use as per study protocol.
• Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

Exclusion Criteria:

• Has received other antitumor therapy before planned start of trial treatment.
• Previously received allogeneic stem cell or parenchymal organ transplantation;
• Previously or currently suffering from congenital or acquired immunodeficiency diseases;
• known or suspected to have a history of allergies to similar drugs such as RC48-ADC and anti-PD-1, or has a history of hypersensitivity to chimeric or humanized antibodies or fusion proteins, or is allergic to excipients of the study drug.
• Diagnosed with HBsAg, HBcAb positive and HBV DNA copy positive, or HCVAb positive, or HIVAb positive.
• Has received a live virus vaccine within 4 weeks of planned start of trial treatment.
• NYHA Class III or IV heart failure.
• Suffering from active infection requiring systemic treatment.
• Uncontrolled hypertension, diabetes, Interstitial lung Disease, or COPD;
• Required systemic treatment with glucocorticoid (>10 mg/day of prednisone or equivalent glucocorticoid) or other immunosuppressive agents within 14 days prior to enter the trial.
• History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or cancers with a similar curative outcome as those mentioned above.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Pregnancy or lactation.
• Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.