urothelial carcinoma
Conditions
Interventions
Treatment Group: Disitamab Vedotin (at a dose of 2 mg/kg each time) + cisplatin (at a dose of 75 mg/m^2 each time) + Toripalimab (at a dose of 3 mg/kg each time), administered once every three weeks.
Sponsors
Beijing Anzhen Hospital, Capital Medical University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Voluntarily sign the informed consent form. The patient or their legal representative shall sign the written informed consent form, be willing to participate in the study, and cooperate with the follow-up. 2. Aged = 18 years old, regardless of gender (male or female). 3. The expected survival period is = 12 weeks. 4. Locally advanced or metastatic urothelial carcinoma (including malignant tumors of the bladder, renal pelvis, and ureter) confirmed by histopathology. 5. The subject can provide the results of PD-L1 and HER2 immunohistochemical tests or corresponding specimens from the primary or metastatic tumor sites; the HER2 expression (HER2 1+, HER2 2+, HER2 3+) in the tumor tissue has been confirmed by previous histopathology and immunohistochemistry. 6. Subjects who have not received previous systemic anti-tumor treatment. 7. Have at least one evaluable lesion as defined by RECIST 1.1 (the long diameter on CT/MR scan is = 10 mm or the short diameter of the enlarged lymph node is = 15 mm). 8. The Eastern Cooperative Oncology Group (ECOG) performance status score is 0 or 1. 9. The organ function level of the subject must meet the following requirements: a. Bone marrow: Absolute neutrophil count (ANC) >= 1.5×10^9/L, platelet count >= 100×10^9/L, hemoglobin >= 80 g/L. No blood transfusion within 4 weeks before the first administration, and no treatment with biological response modifier drugs (such as granulocyte-stimulating factors, erythropoietin, etc.) within 2 weeks before the first administration. b. Liver: For patients without liver metastases, the serum total bilirubin (TBIL) is required to be = 50 mL/min (according to the Cockcroft and Gault formula). d. Coagulation function: International normalized ratio (INR) = 40%. f. Others: Adverse events (AEs) related to previous anti-tumor treatment have recovered to <= Grade 1 as defined in the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) (excluding alopecia, non-clinically significant or asymptomatic laboratory abnormalities). 10. For women of childbearing age, the serum pregnancy test result within 72 hours before the first administration of the study drug is negative. Patients of childbearing age must take effective contraceptive measures from before enrollment in the study until 6 months after the last administration. 11. Enrolled patients must undergo surgical radical resection for eligible patients after completing the scheduled neoadjuvant treatment cycles. The surgical goal is to completely remove the tumor and possible lymph node metastases.
Exclusion criteria
Exclusion criteria: 1. Have received HER2-targeted antibody-drug conjugates or other anti-tumor immunotherapeutic drugs (including immunotherapy with PD-1 or PD-L1 inhibitors) in the past. 2. Known to have an allergic reaction to any component or excipient of MRG002 or HX008 (histidine, histidine hydrochloride monohydrate, sucrose, and polysorbate 80), or known to have an allergic reaction of grade = 3 to other previous anti-HER2 drugs (including investigational drugs in the trial) or to other monoclonal antibodies (PD-1/PD-L1). 3. Have received any of the following treatments: a. Received investigational drugs of other clinical trials within 4 weeks before the first administration. b. Received any anti-tumor drugs/biologics or investigational therapeutic drugs within 4 weeks before the first administration. c. Received radiotherapy within 4 weeks before the first administration. d. Underwent major surgery within 4 weeks before the first administration and has not fully recovered, or planned to undergo major surgery within the first 4 weeks after receiving the investigational drug. 4. Known to have active central nervous system metastases and/or carcinomatous meningitis. 5. Have evidence of active or progressive infections, including hepatitis B (simultaneously meeting the criteria of positive HBsAg and HBV DNA greater than the lower limit of detection, and excluding hepatitis caused by drugs or other reasons), hepatitis C (simultaneously meeting the criteria of positive anti-HCV antibody and HCV RNA result greater than the lower limit of detection), human immunodeficiency virus (HIV) infection, active pulmonary tuberculosis, etc.; there are other severe liver diseases, including chronic autoimmune liver disease, primary biliary cirrhosis or sclerosing cholangitis, alcoholic liver disease, or non-alcoholic steatohepatitis (NASH), etc. 6. Peripheral neuropathy of grade greater than 1. 7. Have poorly controlled heart-related diseases, such as acute myocardial infarction, heart failure of NYHA class 2 or above, unstable angina pectoris, myocardial infarction occurred within 1 year, clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention, QTc > 450 ms (for men) or QTc > 470 ms (for women). 8. Have active autoimmune diseases or a history of autoimmune diseases, are using immunosuppressants, or are receiving systemic hormone therapy (with a dose > 10 mg/day of prednisone or other equivalent hormones), and are still continuing to use them within 2 weeks before enrollment. 9. Have a history of malignant tumors, except for subjects who have received radical treatment and have not relapsed within 5 years after treatment. 10. Have had acute pulmonary embolism or deep vein thrombosis within 3 months before the first administration of the investigational drug. 11. Have uncontrolled pleural effusion, pericardial effusion, or recurrent ascites, and require = 1 drainage per month. 12. Have uncontrolled active bacterial, viral, fungal, rickettsial, or parasitic infections and have not received intravenous antibiotics within 14 days, unless the infection is treated and resolved before the administration of the investigational drug. 13. Have received allogeneic tissue/solid organ transplantation. 14. Have severe pulmonary diseases (including but not limited to severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm, and interstitial lung disease, etc.). 15. Current pregna
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| pathological Complete Response, pCR; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pathological stage (ypT2N0);Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1);EORTC QLQ-C30; | — |
Countries
China
Contacts
Public ContactNing Zhang
Beijing Anzhen Hospital, Capital Medical University
Outcome results
None listed