Study of Multi-mode Thermal Therapy Combined With Immunotherapy In Patients With HER2-negative Breast Cancer With Liver Metastases

Study of Multi-mode Thermal Therapy Combined With Immunotherapy In Patients With HER2-negative Breast Cancer With Liver Metastases: A Prospective, Open-label, Phase II Trial

This is a prospective, open-label, phase II platform trial. The purpose of this study is to test the safety and effectiveness of multi-mode thermal therapy combined with immunotherapy in patients with HER2-negative breast cancer with liver metastases who had previously received systemic therapy

This is a prospective, open-label, phase II trial. The purpose of this study is to test the safety and effectiveness of multi-mode thermal therapy combined with immunotherapy in patients with advanced breast cancer who had previously received systemic therapy. The primary endpoint is progression free survival. Previous studies have shown that multi-mode thermal therapy can elicit systemic anti-tumor immune responses and sensitize immunity. To further validate these findings, we have designed this study to enroll HER2-negative patients who have progressed after conventional treatments (including chemotherapy, immunotherapy, ADC, etc.), with the aim of further investigating the clinical feasibility of multi-mode thermal therapy combined with immunotherapy and ADC therapy in patients with liver metastases in HER2-negative breast cancer.

Inclusion Criteria:

1. Female patients aged ≥ 18 years;
2. Histologically confirmed HER2-negative invasive breast cancer (defined as: HER2 0 or 1+, or HER2 2+ with negative FISH result indicating no amplification);
3. Breast cancer with liver metastasis;
4. Patients who have received and failed ≥ 1 line of systemic therapy after diagnosis of recurrent or metastatic breast cancer, with documented disease progression:

For HR+/HER2- advanced breast cancer: prior CDK4/6 inhibitor therapy in the advanced setting; For HR-/HER2- advanced breast cancer: at least one line of chemotherapy in the advanced setting; 5)At least one measurable lesion per RECIST 1.1 (not previously irradiated) other than the ablation target lesions; 6)Intrahepatic metastatic lesions: number ≤ 10, maximum diameter ≤ 4 cm, no vascular or bile duct invasion; 7)Adequate organ function, meeting the following criteria:

1. Laboratory hematology:

   HB ≥ 90 g/L (without transfusion within 14 days); ANC ≥ 1.5×10⁹/L; PLT ≥ 75×10⁹/L;

2. Laboratory biochemistry:

TBIL ≤ 1.5×ULN (upper limit of normal); ALT and AST ≤ 5×ULN; 8) Expected survival ≥ 12 weeks; 9)Female subjects of childbearing potential must use a medically accepted contraceptive method during study treatment and for at least 3 months after the last dose of study drug.

10)Subjects have voluntarily agreed to participate in this study, signed the informed consent form, are compliant, and willing to comply with follow-up requirements.

Exclusion Criteria:

1. Uncontrolled central nervous system (CNS) metastases, defined as symptomatic metastases or those requiring glucocorticoids or mannitol for symptom control.
2. History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina pectoris, myocardial infarction within the past 6 months, or ventricular arrhythmia.
3. Received radiotherapy or surgical treatment for advanced HER2-negative breast cancer within 1 week prior to the first study drug administration or study procedure.
4. Pregnant or lactating patients.
5. Malignancy diagnosed within the past 3 years, except for cured basal cell carcinoma of the skin and carcinoma in situ of the uterine cervix.
6. Significant comorbidities, including psychiatric disorders that, in the investigator's judgment, would adversely affect the patient's participation in the study.
7. History of gastrointestinal bleeding or definite gastrointestinal bleeding tendency within the previous 6 months, including esophageal varices at risk of bleeding, active local ulcerative lesions, or stool occult blood ≥ ++. Patients with stool occult blood (+) must undergo gastroscopy.
8. Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to study enrollment.
9. Urinalysis showing urine protein ≥ ++ or confirmed 24-hour urinary protein > 1.0 g.
10. Hypertension that cannot be controlled within the normal range by antihypertensive therapy (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg).
11. Patients with allergic constitution, known hypersensitivity to any component of the study drugs, or hypersensitivity to other monoclonal antibodies.
12. Pre-existing thyroid dysfunction.
13. Any other conditions in which the investigator deems the patient unsuitable for participation in this study.