This prospective, single-center, open-label, real-world observational study plans to enroll 10-15 patients with advanced (Stage IV) breast cancer who have failed multiple prior therapies \[aged 18-75, Eastern Cooperative Oncology Group Performance Status Clinical Classification（ECOG） 0-2, with measurable and injectable lesions\]. It aims to preliminarily evaluate the antitumor activity, safety, and immune-microenvironment modulation of intratumoral H101（Recombinant Human Adenovirus Type 5 Injection） oncolytic virus combined with immune checkpoint inhibitors (ICIs) in real-world practice. The regimen is determined by physicians based on clinical status and multidisciplinary input, but follows a standardized framework: 2- to 3-week cycles; H101 injected on day 1 (dose stratified by lesion size), with ICI infusion started 7±2 days later, for 4 planned cycles. Paired tumor biopsies (when feasible) and peripheral blood are collected at baseline and after 4 cycles for single-cell RNA sequencing and immune profiling, focusing on changes in T lymphocyte (T), Natural Killer cell (NK), dendritic, and macrophage subsets and correlating with clinical outcomes. Primary endpoints include adverse events (Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0（CTCAE v5.0）), objective response and local control rates (Response Evaluation Criteria in Solid Tumors Version 1.1（RECIST 1.1）), 4-cycle completion, and toxicity-related discontinuation. Secondary endpoints include disease control rate, progression-free survival (Kaplan-Meier), and dynamic immune changes. First radiological assessment occurs at 6-8 weeks post-treatment, then every 3 months until progression, loss to follow-up, or 1 year. If re-biopsy is unsafe, only peripheral blood may be collected without protocol violation. Comprehensive follow-up, data confidentiality, and missing-data handling are in place to ensure scientific validity and participant protection.
Age 18 to 75 years, both genders;
Pathologically confirmed breast cancer (Stage IV)；
Disease progression after at least one line of standard systemic therapy；
ECOG performance status 0-2；
Known allergy to H101 formulation, PD-1 inhibitors, or any of their excipients ;
Lymphocyte count <0.5×10⁹/L;
Severe infection, active infection (particularly HBV, HCV, HIV), or severely immunocompromised status;
Presence of lesions that cannot be safely punctured/injected;
This study will enroll 15 patients with advanced metastatic breast cancer presenting with multiple metastases, who have failed multiple prior lines of systemic therapy, and are aged 18 to 75 years. Subjects will be primarily recruited from the patient population at Foshan Fosun Chancheng Hospital. All eligible subjects must meet all inclusion criteria and none of the exclusion criteria.
Cohort
Prospective
Not listed
Incidence of Adverse Events
Metric/method of measurement : Common Terminology Criteria for Adverse Events version 5.0
Objective Response Rate
Response Evaluation Criteria in Solid Tumors version 1.1
Local Control Rate
According to clinical and radiological assessment
Treatment Feasibility
Measured by completion rate and adherence rate
Disease Control Rate
Response Evaluation Criteria in Solid Tumors, version 1.1(RECIST 1.1 )
Progression-Free Survival
According to clinical and radiological assessment
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Jie Yuan，MD
Lead sponsor
Foshan Fosun Chancheng Hospital
Sponsor institution
