Overview

This study is a randomized, open-label, controlled, multicenter Phase II trial conducted in patients with advanced HER2-positive breast cancer, aimed at evaluating the efficacy and safety of paclitaxel polymer micelles for injection combined with trastuzumab and adalimumab versus the paclitaxel-based regimen combined with trastuzumab as first-line treatment.

Eligible subjects with histologically or cytologically confirmed advanced HER2-positive breast cancer were enrolled after obtaining informed consent. They were randomly assigned to two groups: the experimental group received paclitaxel polymer micelles for injection combined with trastuzumab, pertuzumab, and adrelumab; the control group received taxanes (paclitaxel, docetaxel, albumin-bound paclitaxel, paclitaxel polymer micelles) combined with trastuzumab and pertuzumab. Each treatment cycle lasted 3 weeks (Q3W), with administration on day 1 (D1) of each cycle. Therapy continued until disease progression (PD), intolerable toxicity, withdrawal of informed consent, initiation of alternative antitumor therapy, death, or any other treatment discontinuation criteria specified in the protocol-whichever occurred first.

Eligibility

1. Age: ≥18 years, no gender restriction;
2. Pathologically confirmed breast cancer: a) Advanced or metastatic breast cancer; b) Locally assessed as HER2-positive (IHC 3+ or IHC 2+ with ISH+);
3. For advanced or metastatic breast cancer, patients should have not previously received chemotherapy or HER2-targeted therapy, or have received only first-line endocrine therapy. Subjects receiving chemotherapy or HER2-targeted therapy as neoadjuvant or adjuvant treatment are eligible if the interval from treatment completion to metastasis diagnosis exceeds 6 months;
4. PD-L1 testing is positive (combined positive score CPS ≥ 1);
5. ECOG score is 0-1;
6. Estimated survival is at least 3 months;
7. There is at least one measurable lesion assessed by computed tomography (CT) and/or magnetic resonance imaging (MRI) (according to RECIST 1.1);
8. Basic normal function of major organs such as the heart, lungs, liver, and kidneys;
9. Sufficient organ and bone marrow function, meeting the following criteria: (1) Complete blood count must meet: a) Hemoglobin (HB) ≥ 90 g/L; b) Absolute neutrophil count (ANC) ≥ 1.5×10⁹/L; c) Platelet count (PLT) ≥ 75×10⁹/L; (2) Biochemical tests must meet: a) Serum total bilirubin (TBIL) ≤ 1.5× upper limit of normal (ULN); b) ALT and AST ≤ 2.5× ULN; if liver metastases are present, ALT and AST ≤ 5× ULN; c) Cr ≤ 1.5× ULN or creatinine clearance (CCr) ≥ 60 mL/min (Cockcroft-Gault formula);
10. Patients voluntarily participate in the study, sign an informed consent form, and demonstrate good compliance.

Exclusion Criteria:

Subjects were ineligible for this trial if they met any of the following criteria:

1. Known allergy or intolerance to any study agent or excipient;
2. Primary central nervous system malignancy or meningeal metastasis; symptomatic patients with central nervous system metastases; patients with asymptomatic brain metastases or clinically stable conditions requiring no steroid therapy for at least 4 weeks were eligible;
3. History of chemotherapy, targeted therapy, or major surgery within 4 weeks prior to first dose; history of endocrine therapy or local radiotherapy within 2 weeks prior to first dose;
4. Active or previously documented interstitial lung disease (ILD), pneumonia, or suspected ILD that could not be excluded by imaging during screening; pneumonia that could not be excluded by imaging during screening;
5. History of other malignancies within 5 years that could be locally treated and cured (excluding basal cell carcinoma of the skin, superficial or non-invasive bladder cancer, cervical carcinoma in situ, breast ductal carcinoma in situ, papillary thyroid carcinoma, etc.);
6. History of live vaccine vaccination within 28 days prior to treatment;
7. Active autoimmune diseases (including but not limited to myasthenia gravis, myositis, asthma, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vitiligo, psoriasis, etc.); stable-dose hormone replacement therapy for hypothyroidism was excluded;
8. Patients with significant coagulation disorders or other clear evidence of bleeding risk.
9. Patients with the following cardiac conditions within 6 months prior to treatment initiation: acute coronary syndrome, coronary artery bypass grafting, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular events; cardiac dysfunction classified ≥ Class II on the New York Heart Association (NYHA) scale or left ventricular ejection fraction (LVEF) \<50%; myocardial infarction, severe/unstable angina, cerebrovascular accident/stroke, transient ischemic attack, subarachnoid hemorrhage, or severe cardiac rhythm/conductance abnormalities requiring clinical intervention (e.g., ventricular arrhythmias, second-to-third-degree atrioventricular block, congenital long QT syndrome);
10. Patients with active hepatitis B or C virus infection, HIV infection, or active pulmonary tuberculosis;
11. Patients with active infections requiring antimicrobial therapy (e.g., antibiotics, antiviral agents, or antifungal drugs);
12. Patients with a known history of allogeneic organ transplantation or hematopoietic stem cell transplantation;
13. Patients with a history of substance abuse (e.g., psychiatric medications) that cannot be discontinued or those with mental disorders;
14. Pregnant or breastfeeding women; or patients of reproductive age who are unwilling or unable to use effective contraceptive measures.