A Phase II Clinical Study of Multimodal Ablation Combined With Systemic Drug Therapy for Advanced Solid Tumors.

Exclusion Criteria

• •1. Patients with known allergy or suspected allergy to the study drugs or similar drugs;
• •2. Patients who have participated in another clinical study and received at least one treatment within 4 weeks prior to enrollment;
• •3. History or concurrent presence of other malignant tumors(except for cured basal cell carcinoma of the skin,superficial bladder cancer,carcinoma in situ of the cervix,and papillary thyroid carcinoma);
• •4. Patients with immunodeficiency diseases within 7 days prior to the first dose,or currently receiving systemic corticosteroid therapy(≥10mg/day prednisone or equivalent dose of other corticosteroids),or other forms of immunosuppressive therapy;
• •5. Symptomatic central nervous system(CNS)metastases,or other evidence indicating that the CNS metastases have not been controlled,and deemed unsuitable for enrollment by the investigator;
• •6. Patients who have previously undergone organ or bone marrow transplantation;
• •7. Uncontrollable pleural effusion,pericardial effusion,or ascites causing respiratory syndrome(≥CTCAE grade 2 dyspnea);
• •8. Esophageal(gastric fundus)variceal rupture bleeding within the last month;
• •9. Other antitumor treatments outside the combined regimen,such as radiotherapy,systemic chemotherapy,etc.;
• •10. Clinically significant electrolyte abnormalities as judged by the investigator;
• •11. Insufficiency or failure of major organs;
• •12. Patients who have received systemic drug therapy,radiotherapy,or local liver treatment,with a time interval of less than 1 month since the last systemic treatment or local liver treatment;
• •13. Patients who have received immunotherapy and experienced grade 3 or higher immune-related adverse events(irAEs)(except for thyroid function abnormalities,blood sugar abnormalities);
• •14. Active or uncontrolled severe infections(≥CTCAE grade 2 infections);
• •15. Any other disease,clinically significant metabolic abnormalities,physical examination abnormalities,or laboratory test abnormalities that,in the investigator's judgment,may have a disease or condition that makes the patient unsuitable for the study drug,or may affect the interpretation of the study results,or may place the patient at high risk;
• •16. Pregnant or breastfeeding women,or women of childbearing age with a positive baseline pregnancy test;
• •17. Known human immunodeficiency virus(HIV)infection;known clinically significant liver disease history,including viral hepatitis\[known carriers of hepatitis B virus(HBV)must exclude active HBV infection,i.e.,HBV DNA positive(\>1×10\^4 copies/mL or\>2000 IU/mL);known hepatitis C virus(HCV)infection and HCV RNA positive(\>1×10\^3 copies/mL),or other hepatitis,cirrhosis;
• •18. Patients with severe heart,lung,liver,or kidney dysfunction,irreversible coagulation disorders,or other uncontrolled diseases(including hypertension or diabetes,active infections,mental illness,or social conditions that may affect patient compliance);
• •19. Other factors that may affect patient safety or trial compliance as judged by the investigator.
• •1. Colorectal Cancer :
• •a) Patients with uncontrolled hypertension, defined as: patients with hypertension that cannot be well-controlled with a single antihypertensive agent (SBP ≥150 mmHg or DBP ≥100 mmHg); or patients who require two or more antihypertensive medications to control blood pressure.
• •b）Patients with urine dipstick proteinuria ≥2+ and a 24-hour urinary protein level \>1.0 g.
• •c）Patients with gastrointestinal diseases such as active gastric or duodenal ulcers, ulcerative colitis, or active bleeding from an unresected tumor; or other conditions judged by the investigator as potentially causing gastrointestinal bleeding or perforation.
• •d）Patients with evidence or history of a significant bleeding tendency within 3 months prior to enrollment (e.g., bleeding \>30 mL, hematemesis, melena, hematochezia), hemoptysis (\>5 mL of fresh blood within 4 weeks), or a thromboembolic event (including stroke and/or transient ischemic attack) within the past 12 months.
• •e）Patients with clinically significant cardiovascular disease, including but not limited to, acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting within 6 months prior to enrollment.
• •f）Congestive heart failure of New York Heart Association (NYHA) class \> II; ventricular arrhythmias requiring medication; or an ECG showing a QTc interval ≥480 milliseconds.
• •g）Patients who are unable to take fruquintinib orally.
• •2. Triple-negative breast cancer :
• •a) Patients who have previously received Pucotenlimab treatment;
• •3. Melanoma :
• •1. Patients who have previously received Pucotenlimab treatment;
• •2. Patients currently have uncontrolled hypertension,defined as:patients with hypertension that cannot be well controlled with monotherapy(systolic blood pressure≥150 mmHg,or diastolic blood pressure≥100 mmHg);or patients using two or more antihypertensive drugs to control blood pressure;
• •3. Urine routine indicates proteinuria≥2+,and 24-hour urine protein\>1.0g;
• •4. Significant clinically meaningful cardiovascular diseases,including but not limited to acute myocardial infarction,severe/unstable angina,or coronary artery bypass grafting within 6 months before enrollment;
• •5. Congestive heart failure New York Heart Association(NYHA)classification\>2;ventricular arrhythmias requiring drug treatment;electrocardiogram(ECG)showing QTc interval≥480 milliseconds.