Histopathologically confirmed squamous cell carcinoma of the urogenital system (urethra, penis, kidney, ureter, bladder, etc.) that is unresectable due to recurrence or metastasis
Conditions
Interventions
Trial group:Margetuximab (MRG003): 2.0 mg/kg, once every 3 weeks, Day 1, intravenous infusion
HX008: 200 mg per dose, once every 3 weeks, Day 1, intravenous infusion
Sponsors
Zhejiang Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Patients voluntarily participate in the trial, provide full informed consent, and sign a written informed consent form, And the compliance is good; 2. Aged >=18 years, with no gender preference for males or females; 3. Histopathologically confirmed squamous cell carcinoma of the urogenital system (urethra, penis, kidney, ureter, bladder, etc.) that is unresectable due to recurrence or metastasis; 4. Subjects who have received at least one line of systemic chemotherapy after being diagnosed with locally advanced or metastatic disease that is unresectable, and have experienced disease progression. 5. Archived or biopsy tumor specimens (primary or metastatic lesions) are available, and the patient's tumor specimen is confirmed to be EGFR-positive (IHC >= 1+) by pathological laboratory testing; 6. At baseline, there is at least one measurable target lesion outside the primary lesion according to RECIST v1.1, which is suitable for repeated and accurate measurement and has not undergone local treatments such as radiotherapy; 7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-1; 8. The interval between the last systemic anti-tumor treatment and the first administration of study drug should be at least 5 half-lives or 4 weeks, whichever is shorter; 9. Patients who have progressed after achieving a best response of CR, PR, or SD for >=3 months during initial treatment are required; 10. Expected survival duration >= 12 weeks; 11. The organs and bone marrow possess sufficient functionality and meet the following requirements (prior to initiating research treatment) Within 14 days before treatment: 1) Blood routine examination: (No blood transfusion or use of granulocyte colony-stimulating factor within 14 days before screening) Stimulator [G-CSF], no drug correction used): Hemoglobin [HB] >=90g/L; middle Absolute neutrophil count [ANC] >=1.5×10^9/L; Platelet count [PLT] >=75×10^9/L; 2) Blood biochemical examination must meet the following criteria (no albumin transfusion within 14 days prior to screening): blood Total bilirubin [BIL] =50ml/min (Cockcroft-Gault formula) For males: Creatinine clearance rate = ((140 - age) × weight) / (72 × serum creatinine) Female: Creatinine clearance rate = ((140 - age) × weight) / (72 × serum creatinine) × 0.85 (Weight unit: kg; Blood Cr unit: mg/mL). 3) Coagulation function: International Normalized Ratio (INR) <= 2 or prothrombin time (PT) Exceeding the upper limit of the normal range for <=6 seconds; female subjects with fertility must undergo urine testing within 7 days prior to the first dose Or serum pregnancy test (if the urine pregnancy test result cannot be confirmed as negative, a blood test is required) Conduct a pregnancy test, with the serum pregnancy test result as the criterion, and ensure that the result is negative; 12. If a female subject with fertility engages in sexual activity with an unneutered male partner, she must adopt an acceptable contraceptive method from the beginning of screening and agree to continue using the contraceptive method for 180 days after the last administration of the study drug; 13. If a male subject who has not been sterilized engages in sexual activity with a female partner who is capable of bearing children, the subje
Exclusion criteria
Exclusion criteria: 1. The presence of symptomatic or untreated known brain metastases or other central nervous system (CNS) metastases, as well as CNS metastases proven to be stable or improving after complete resection and/or radiotherapy, are not exclusion criteria. As long as computed tomography (CT) scans show stability for at least 4 weeks prior to screening, with no evidence of brain edema and no need for corticosteroids or anticonvulsants, they can be included; 2. Apart from squamous cell carcinoma of the urogenital system (urethra, penis, kidney, ureter, bladder, etc.), the subject has suffered from other malignant tumors within 3 years prior to enrollment; excluding thyroid microcarcinoma, cutaneous squamous cell carcinoma, and other in situ cancers, except for those that have been cured. 3. Patients who have previously received treatment with CTLA-4 antibodies, bispecific immunotherapies targeting CTLA-4, or ADC drugs; 4. Previous discontinuation of treatment due to severe and/or life-threatening immunotherapy-related toxicity; 5. The adverse reactions caused by previous anti-tumor treatment have not recovered to grade 10 mg/day of prednisone or equivalent) within 2 weeks prior to the first use of study medication; in the absence of active autoimmune disease, the use of inhaled or topical steroids and adrenal cortical hormone substitutes with a dose >10 mg/day of prednisone or equivalent is allowed for inclusion; b) Having received attenuated live vaccines within 4 weeks prior to the first use of study medication, or planning to receive live vaccines or attenuated live vaccines during the study period; c) Having undergone major surgery or severe trauma within 4 weeks prior to the first use of study medication; 7. Patients with any active autoimmune disease or history of autoimmune disease, including but not limited to: interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (may be considered after hormone replacement therapy); patients with psoriasis or childhood asthma/allergy that have been completely alleviated and do not require any intervention in adulthood may be considered for inclusion, but patients requiring medical intervention with bronchodilators are not eligible for inclusion; 8. History of immune deficiency, including HIV-positive test result, or suffering from other acquired or congenital immune deficiency diseases, or history of organ transplantation or allogeneic bone marrow transplantation; 9. Presence of uncontrolled cardiac clinical symptoms or diseases, including but not limited to: NYHA class II or higher heart failure, unstable angina pectoris, myocardial infarction within one year, and clinically significant supraventricular or ventricular arrhythmias that have not been clinically intervened or remain poorly controlled after clinical intervention; 10. Severe infections (CTCAE > Grade 2) occurred within 4 weeks before the first use of study drug, such as severe pneumonia requiring hospitalization, bacteremia, and infection complications; baseline chest imaging indicated active pulmonary inflammation, presence of s
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR);Disease Control Rate (DCR);Progression-Free Survival (PFS);Overall Survival (OS); | — |
Countries
China
Contacts
Public ContactFang Meiyu
Zhejiang Cancer Hospital
Outcome results
None listed