Cryoablation Combined With Hepatic Arterial Infusion of Iparomlimab and Tuvonralimab (QL1706), Intravenous Dacarbazine, and Oral Lenvatinib in Patients With Liver Metastases From Malignant Melanoma: a Single-arm, Phase II, Prospective Trial

Ki vehet részt

• Age 18-70 years
• Patients with pathologically confirmed metastatic malignant melanoma after failure of standard treatment
• Presence of liver metastases, with at least one lesion assessed as suitable for cryoablation
• The largest diameter of each intrahepatic metastatic lesion < 5 cm
• At least one target lesion suitable for efficacy assessment according to RECIST 1.1 (when no appropriate extrahepatic target lesion is available, a non-ablated intrahepatic lesion may serve as the observation lesion)
• ECOG performance status score of 0
• No history of autoimmune disease
• Life expectancy of more than 3 months
• Laboratory test results meeting the following criteria:; Neutrophil count >= 1.8 × 10⁹/L; White blood cell count >= 3.0 × 10⁹/L; Platelet count >= 100 × 10⁹/L; Hemoglobin >= 90 g/L; Serum ALT and AST <= 2.5 × the upper limit of normal (ULN); Serum creatinine <= 1.5 × ULN; INR < 1.3 or prothrombin time < ULN + 2 seconds; Albumin >= 35 g/L; Total bilirubin <= 1.0 × ULN

Ki nem vehet részt

• Liver metastases previously treated with radiotherapy, microwave ablation, radiofrequency ablation, or irreversible electroporation
• Known central nervous system metastases that are clinically unstable, or acute meningitis (except patients with central nervous system metastases who have received treatment and are clinically stable); Clinical stability requires all of the following:
• Child-Pugh score >= 7; decompensated liver function, such as massive ascites, gastric fundal or esophageal varices with upper gastrointestinal bleeding within the previous year, hepatic encephalopathy, or bilirubin encephalopathy
• no new neurological symptoms, and previous neurological symptoms have returned to normal; Previous treatment with immune checkpoint inhibitors complicated by grade 3 or higher immune-related adverse events; Pregnant or breastfeeding women; History of HIV infection; History of another malignancy within 5 years (excluding early-stage basal cell carcinoma, carcinoma in situ of the cervix, and papillary thyroid carcinoma); Any of the following within 12 months before study initiation: myocardial infarction, severe or unstable angina, congestive heart failure, cerebrovascular accident, or pulmonary embolism; Severe hepatic or renal impairment; uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, or acute pulmonary disease; poorly controlled hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 90 mmHg); clinically significant cardiovascular or cerebrovascular disease, such as cerebrovascular accident or myocardial infarction within 6 months, unstable angina, NYHA class II or higher congestive heart failure, severe arrhythmia not controlled by medication, clinically significant electrocardiographic abnormalities on three consecutive recordings obtained at least 5 minutes apart, psychiatric disorders, or drug abuse; or any condition that the investigator considers likely to increase risk to the subject or interfere with study results; History of organ transplantation; Other severe acute or chronic physical or psychiatric illnesses, or laboratory abnormalities, that may increase study-related risk or interfere with interpretation of results and make the patient unsuitable for enrollment; Uncontrolled concurrent diseases or infectious diseases. Patients with active hepatitis B must receive antiviral therapy to achieve HBV DNA < 500 copies/mL and remain stable for at least 2 weeks before the investigator assesses eligibility, and must continue antiviral therapy throughout the study after enrollment; History of severe adverse reactions to contrast agents; Any active autoimmune disease, or a history of autoimmune disease judged by the investigator to make the patient unsuitable for this study, including but not limited to systemic lupus erythematosus, immune-related neuropathy, multiple sclerosis, Guillain-Barre syndrome, myasthenia gravis, connective tissue diseases, and inflammatory bowel disease including Crohn's disease and ulcerative colitis; Previous treatment with lenvatinib or other multi-target tyrosine kinase inhibitors; Previous systemic chemotherapy containing dacarbazine or temozolomide complicated by grade 3 or higher myelosuppression or hepatotoxicity during treatment; Total intrahepatic lesion volume assessed by the investigator as exceeding 50% of the total liver volume; Use of therapeutic anticoagulants (such as warfarin, direct oral anticoagulants, or low-molecular-weight heparin) or dual antiplatelet therapy (such as aspirin combined with clopidogrel) within 7 days before enrollment, if the medications cannot be safely discontinued and bridged before cryoablation and arterial infusion
• ECOG performance status score >= 2
• no new brain lesions and no enlargement of existing lesions, confirmed by MRI
• no glucocorticoid treatment for at least 2 weeks