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

Launched by FUDAN UNIVERSITY · Mar 19, 2025

Keywords

ClinConnect Summary

This clinical trial is exploring a new treatment approach for patients with advanced liver cancer caused by triple-negative breast cancer or melanoma. The study aims to combine a technique called multimodal ablation, which helps target and destroy tumors, with a drug called pucotenlimab that boosts the body's immune response. This combination is hoped to improve treatment outcomes for patients who have limited options due to their cancer spreading to the liver.

To participate in this trial, individuals must be between 18 and 80 years old, have at least three liver tumors, and be in relatively good health with a life expectancy of at least three months. Patients with confirmed triple-negative breast cancer must have already tried standard treatments without success, while those with melanoma should have liver tumors that cannot be surgically removed. Participants can expect to undergo this new treatment and will be monitored for its effectiveness and safety. It’s important to note that anyone who has had certain other health conditions or treatments may not be eligible to join this trial.

Gender

ALL

Eligibility criteria

• Inclusion Criteria i. Common eligibility criteria for all two cohorts: 1. Age between 18-80 years,gender not limited; 2. The number of liver metastases is≥3.Besides the ablation lesions,there must be at least one measurable lesion(≥1cm),and the diameter of the ablation lesions is\<5cm; 3. Expected survival≥3 months; 4. ECOG performance status score of 0-1; 5. Within 14 days before the first dose,laboratory tests indicate adequate organ function:
• a) Hematology:WBC≥3.0×10\^9/L;ANC≥1.5×10\^9/L;PLT≥75×10\^9/L;HGB≥90 g/L b) Liver function:Child-Pugh score≤7,AST≤5.0×ULN;ALT≤5.0×ULN;TBIL≤1.5×ULN c) Renal function:Cr≤1.5×ULN or CrCl≥60 mL/min d) Coagulation function:INR≤1.5×ULN(for patients on anticoagulant therapy,≤3×ULN,anticoagulants must be discontinued one week before ablation);APTT≤1.5×ULN ii. Additional eligibility criteria for each cohort:
• 1. Triple-negative breast cancer :
• • 1. Clinically or pathologically confirmed triple-negative breast cancer(triple-negative defined as\<1% nuclear staining for ER and PR expression and HER2 negative);
• • 2. Patients who have failed standard second-line drug therapy(including those who have failed PD-1 monoclonal antibody therapy, with progression within six months of adjuvant or neoadjuvant therapy considered as first-line therapy failure).
• 2. Melanoma :
• • 1. Clinically or pathologically confirmed melanoma liver metastasis, with inoperable or intolerable liver lesions or refusal of surgical resection;
• • 2. Patients who have failed standard first-line drug therapy.
• Exclusion Criteria:
• i. Common exclusion criteria for all two cohorts:
• • 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.
• ii. Additional exclusion criteria for each cohort:
• 1. Triple-negative breast cancer :
• • a) Patients who have previously received Pucotenlimab treatment;
• 2. 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.