Urothelial Cancer Clinical Trials

• All subjects voluntarily participated in the study and signed informed consent;

• Male or female aged ≥18 years and ≤75 years;

• Expected survival time ≥3 months;

• ECOG 0-1;

• Locally advanced or metastatic urothelial carcinoma and other solid tumors confirmed by histopathology and/or cytology who have failed or cannot tolerate standard treatment or who currently have no standard treatment or cannot obtain standard treatment; (including but not limited to urothelial cancer, prostate cancer, kidney cancer) : ① Urothelial cancer should have received previous failure or intolerance to standard platinum-based chemotherapy; ② Prostate cancer with pathological type of adenocarcinoma should have received at least one previous novel hormonal therapy (abiraterone acetate, enzalutamide, etc.) and at least one failed or intolerant taxane regimen (docetaxel, cabazitaxel); ③ Clear cell renal cell carcinoma required previous failure or intolerance to standard first-line tyrosine kinase inhibitor (TKI) regimens. ④ Locally advanced or metastatic other urological malignancies (non-clear cell renal cancer, penile cancer, etc.) that failed standard treatment and were not suitable for surgery or radiotherapy. Treatment failure was defined as disease progression during or after treatment with systemic antitumor regimens. Intolerance refers to patients who have received standard treatment and have grade 3-4 adverse reactions, and refuse to continue the original regimen.

• Note: Recurrence or disease progression within 6 months of the last chemotherapy in multimodal therapy was considered as first-line treatment.

• Consent to provide archival tumor tissue specimens (10 unstained sections (anti-slip) surgical specimens (thickness 4-5μm)) or fresh tissue samples from primary or metastatic lesions within 3 years. If participants cannot provide tumor tissue samples, they can be enrolled if they meet other inclusion and exclusion criteria, after the evaluation of the investigator;

• Must have at least one measurable lesion according to RECIST v1.1 definition; Lesions that had been previously treated with radiation could be included in a measurable lesion only if there was definite disease progression after radiation therapy.

• Provided that no blood transfusions and no use of any cell growth factors and/or platelet-raising agents are allowed for 14 days prior to the screening period, organ function levels must meet the following criteria:

∙ Blood routine: hemoglobin (HGB) ≥ 90g/L; Absolute neutrophil count (NEUT) ≥1.5×10 9 /L; Platelet count (PLT) ≥ 100×10 9 /L;

‣ Renal function: creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥40 mL/min (according to Cockcroft and Gault formula).

‣ Liver function: total bilirubin (TBIL≤1.5 ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were all ≤2.5 ULN, and AST and ALT were both ≤5.0 ULN when liver metastasis was present;

‣ Coagulation function: international normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5ULN;

‣ no severe cardiac dysfunction with left ventricular ejection fraction ≥50%;

• Toxicity from previous antineoplastic therapy has returned to grade 1 or less as defined by NCI-CTCAE v5.0 (asymptomatic laboratory abnormalities such as ALP elevation, hyperuricemia, and hyperglycemia were considered by the investigator, and toxicity with no safety risk was judged by the investigator; Except for alopecia, grade 2 peripheral neurotoxicity, or decreased hemoglobin ≥90g/L).

⁃ For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before the start of treatment, the serum or urine pregnancy test must be negative, and the patient must not be lactating; All enrolled patients should take adequate barrier contraception during the entire treatment cycle and for 6 months after the end of treatment.