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

Study Overview

• Status: Not yet recruiting
• Conditions: HER2-negative Breast Cancer
• Intervention / Treatment: Drug: SHR-A1811; Drug: SKB264; Drug: Pembrolizumab; Drug: SHR-1316

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: zhimin shao, MD; Phone Number: 86-021-64175590; Email: zhimingshao@yahoo.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Breast cancer institute of Fudan University Cancer Hospital
      • Contact: Zhimin Shao, MD; Phone Number: 86-21-64175590; Email: Zhimingshao@yahoo.com
      • Principal Investigator: Zhimin shao, MD
      • Sub-Investigator: Jianjing hou, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HER2(0); Pembrolizumab + SKB264（Trop2 ADC）	Drug: SKB264; A TROP2-directed ADC, via intravenous (into the vein) infusion per protocol.; Drug: Pembrolizumab; PD-1 antibody, via intravenous (into the vein) infusion per protocol.
Experimental: HER2-low; SHR1316(PD-L1 antibody) + SHR-A1811(HER2 ADC)	Drug: SHR-A1811; A HER2-directed ADC, via intravenous (into the vein) infusion per protocol.; Drug: SHR-1316; PD-L1 antibody, via intravenous (into the vein) infusion per protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS based on Kaplan-Meier methodology will be defined as the time from randomization until the identification of disease progression or death, whichever occurs first. Subjects without disease progression or death at the time of analysis will be censored at the date of last disease evaluation.	The observation period related to this endpoint is up to 12 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Objective response rate (ORR), defined as best overall response of either complete or partial response, will be assessed among participants who start protocol therapy and have measurable disease at screening. Radiographic response will be assessed using RECIST 1.1 criteria as defined per protocol.	The observation period related to this endpoint is up to 12 months.
Overall Survival (OS)	Overall survival based on the Kaplan-Meier method is defined as the time from randomization to death. Participants alive are censored at the last date of contact (including lost-to-follow-up) or at the date of withdrawal of consent, if relevant.	The observation period related to this endpoint is up to 2 years.

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): March 15, 2026
• Primary Completion (Estimated): January 15, 2028
• Study Completion (Estimated): January 15, 2029

Study Registration Dates

• First Submitted: March 9, 2026
• First Submitted That Met QC Criteria: March 9, 2026
• First Posted (Actual): March 12, 2026

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; HER2-negative Breast Cancer; Multi-mode Thermal Therapy
• Additional Relevant MeSH Terms: pembrolizumab
• Other Study ID Numbers: SCHBCC-N0109

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No