QUEEN-APPLE: A Single-Arm, Multicenter, Prospective Phase II Clinical Study of Iparomlimab and Tuvonralimab (QL1706) in Combination With Anlotinib Hydrochloride and Nab-Paclitaxel as First-Line Treatment for Advanced Triple-Negative Breast Cancer

Exclusion Criteria

• •1. Known history of severe allergic reactions to QL1706, anlotinib, nab-paclitaxel, or any of their excipients.
• •2. Inability to swallow oral medications, or any gastrointestinal disorder that may interfere with the absorption and metabolism of the study drugs.
• •3. Symptomatic brain/leptomeningeal metastases and/or spinal cord metastases.
• •4. Active or potentially relapsing autoimmune disease, with the following exceptions: vitiligo, alopecia, psoriasis, or eczema not requiring systemic treatment; hypothyroidism due to autoimmune thyroiditis requiring only stable-dose hormone replacement therapy; type I diabetes mellitus requiring only stable-dose insulin replacement therapy.
• •5. Major surgery within 3 weeks before study initiation, or failure to recover from surgery.
• •6. History of organ transplantation or autologous/allogeneic stem cell transplantation.
• •7. Known or self-reported human immunodeficiency virus (HIV) infection.
• •8. HBV-DNA positive or HCV-DNA positive (copy number \>10³).
• •9. Prior treatment with any agent targeting the mechanism of tumor immunotherapy, including immune checkpoint inhibitors (e.g., anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-CTLA-4 antibodies), immune checkpoint agonists (e.g., antibodies targeting ICOS, CD40, CD137, GITR, OX40), or immune cell therapy.
• •10. Prior treatment with anti-angiogenic targeted therapy.
• •11. Hypertension that cannot be well controlled with a single antihypertensive medication (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥90 mmHg).
• •12. Arterial/venous thrombotic events (e.g., cerebrovascular accident including transient ischemic attack, deep vein thrombosis, pulmonary embolism) within 6 months before enrollment.
• •13. Presence of other malignancies within 5 years before enrollment, except for TNBC.
• •14. Tumor invasion or compression of surrounding major blood vessels or organs.
• •15. Active central nervous system (CNS) metastatic lesions.
• •16. Clinically significant pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
• •17. History of myocarditis, cardiomyopathy, or malignant arrhythmias.
• •18. History of significant bleeding tendency or coagulation dysfunction.
• •19. History of esophageal-gastric varices, severe ulcer, non-healing wound, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding within 6 months before the first dose.
• •20. Known active tuberculosis (TB).
• •21. History of or current non-infectious pneumonitis/interstitial lung disease requiring systemic corticosteroid therapy.
• •22. Major surgery or severe trauma within 30 days before the first dose, or planned major surgery within 30 days after the first dose; minor local surgery within 3 days before the first dose.
• •23. Platelet or red blood cell transfusion within 4 weeks before initiation of study drug treatment.
• •24. Receipt of live vaccine within 4 weeks before the first dose, or planned receipt of live vaccine during the study.
• •25. Female participants who are pregnant, breastfeeding, or planning to become pregnant during the study.
• •26. Patients judged by the investigator to be unsuitable for participation in this study.