urothelium carcinoma
Conditions
Interventions
Test group:MRG002 is a lyophilized powder for injection. Intravenous infusion, once every three weeks (Q3W).
HX008 is an injection. Intravenous infusion, once every three weeks (Q3W).
Dose escalation
Sponsors
Peking University Cancer Hospital and Institute
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Voluntary signing of the informed consent form and compliance with the protocol requirements; 2. Age >= 18 years and = 12 weeks; 4. Histopathologically confirmed locally advanced or metastatic urothelial carcinoma (including bladder, ureter, renal pelvis and urethra origin) that is inoperable or has recurred after surgery; 5. Subjects who have not received systemic anti-tumor treatment but are intolerant or unsuitable for platinum-based chemotherapy; or those who have received at least one line of systemic chemotherapy during the recurrent/metastatic stage and have experienced disease progression, including those who have experienced disease progression within 12 months after neoadjuvant or adjuvant chemotherapy, can be enrolled in this clinical study; Subjects intolerant to platinum-based chemotherapy should meet one of the following criteria: (1) Creatinine clearance rate (CrCl) calculated by the Cockcroft-Gault formula = grade 2 or peripheral neuropathy >= grade 2; 6. Subjects must be able to provide tumor primary or metastatic site specimens for PD-L1 and HER2 testing; and the tumor tissue HER2 expression (IHC 3+, IHC 2+, IHC 1+) has been confirmed by previous examination or the central laboratory; 7. Have at least one measurable lesion as defined by RECIST 1.1 (CT scan long diameter >= 10 mm or short diameter of enlarged lymph nodes >= 15 mm); 8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; 9. Organ function levels must meet the following requirements: ? Bone marrow: Absolute neutrophil count (ANC) >= 1.5×10^9/L, platelet count >= 100×10^9/L, hemoglobin >= 90 g/L, and no blood transfusion or treatment with biological response modifiers (such as granulocyte or erythropoietin growth factors) within 4 weeks before the first dose/randomization; ? Liver: For patients without liver metastasis, serum total bilirubin (TBIL) = 50 mL/min (calculated by the Cockcroft and Gault formula); ? Coagulation function: International normalized ratio (INR) = 50%; ? Others: Previous anti-tumor treatment-related adverse events have recovered to <= grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) (except for alopecia, non-clinically significant or asymptomatic laboratory abnormalities); Fertile women must have a negative serum pregnancy test result within 72 hours before the first dose of the study drug. Pregnant or lactating women are not eligible for enrollment. Fertile patients must use effective contraceptive measures during the study and for 6 months after the last dose.
Exclusion criteria
Exclusion criteria: 1. Previous treatment with HER2-targeted antibody-drug conjugates or other anti-tumor immunotherapy drugs (including PD-1 or PD-L1 inhibitor immunotherapy); 2. Known hypersensitivity to any component or excipient of MRG002 or HX008 (histidine, histidine hydrochloride monohydrate, sucrose, and polysorbate 80), or known hypersensitivity to other previous anti-HER2 drugs (including investigational study drugs) or to other monoclonal antibodies (PD-1/PD-L1) of grade >= 3; 3. Received any of the following treatments: - Received investigational study drugs in any other clinical trial within 4 weeks before the first dose; - Received any anti-tumor drugs/biologics or investigational treatment drugs within 4 weeks before the first dose (for small molecule targeted drugs, the non-participation period is 2 weeks or 5 half-lives, whichever is longer; for cytotoxic drugs, the non-participation period is 3 weeks); - Received radiotherapy within 4 weeks before the first dose; - Received strong CYP3A4 inhibitors or inducers within 2 weeks before the first dose or currently need to use them; - Underwent major surgery within 4 weeks before the first dose and has not fully recovered, or plans to undergo major surgery within the first 12 weeks after receiving the study drug; 4. Known active CNS metastases and/or carcinomatous meningitis. Subjects with treated brain metastases may participate in the study if the condition is stable and there is no evidence of progressive or new neurological deficits, seizures, increased intracranial pressure, papilledema, vomiting, or headache; MRI within at least 4 weeks before the first dose of the study drug shows no evidence of recurrence/progression, and any neurological symptoms have not returned to baseline; there is evidence of new brain metastases or enlargement of existing brain metastases, and corticosteroids have been used within at least 3 days before the study drug administration. This exclusion does not include patients with carcinomatous meningitis, who should be excluded regardless of stability. 5. Evidence of active or progressive infection, including hepatitis B (must be HBsAg positive and HBV DNA greater than the lower limit of detection, and exclude drug-induced or other causes of hepatitis), hepatitis C (must be anti-HCV antibody positive and HCV RNA result greater than the lower limit of detection), human immunodeficiency virus (HIV) infection, active tuberculosis, etc.; presence of other severe liver diseases, including chronic autoimmune liver disease, primary biliary cirrhosis or sclerosing cholangitis, alcoholic liver disease or NASH, etc. 6. Peripheral neuropathy greater than grade 1; 7. Presence of uncontrolled cardiac clinical symptoms or diseases, such as NYHA class 2 or above heart failure, unstable angina, myocardial infarction within 1 year, clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention, QTc > 450 ms (male) or QTc > 470 ms (female); 8. History of malignant tumors, except for skin basal cell carcinoma, skin squamous cell carcinoma, in situ cervical cancer, or papillary thyroid cancer, or subjects who have received radical treatment and have not relapsed within 5 years of treatment; 9. Presence of active autoimmune disease or history of autoimmune disease, currently using immunosuppressants or systemic hormone therapy (dose > 10 mg/day of prednisone or other equivalent hormones), and still using them within 2 weeks before enrollment. .
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Recommended Phase 2 Dose, RP2D;Objective Response Rate, ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| PK characteristics and immunogenicity;Disease Control Rate;Duration of Response;Progression-Free Survival;Overall Survival; | — |
Countries
China
Contacts
Public ContactGuo Jun
Peking University Cancer Hospital and Institute
Outcome results
None listed