A Trial of HRS-2189 in Combination With Fluvastatin±HRS-6209, or HRS-8080±HRS-6209, or HRS-6209+HRS-1358 in Breast Cancer Patients

Exclusion Criteria

• •1. Patients with active (uncontrolled or symptomatic) brain metastases, cancerous meningitis, spinal cord compression, or a history of primary CNS tumors; patients with brain metastases who have completed treatment at least 28 days prior to first use of the study drug and are asymptomatic can be considered for enrollment if they have been confirmed asymptomatic by cranial imaging studies such as CT, MRI, or venography without evidence of cerebral hemorrhage, and have completed treatment at least 28 days before the first use of the study drug.
• •2. Patients with a history of severe cardiovascular disease, including: (1) Congestive heart failure (NYHA Class\>2); (2) Severe/unstable angina, new angina within the last 3 months; (3) Myocardial ischemia requiring long-term medication control; patients with NYHA Class III-IV heart failure; (4) Acute myocardial infarction within the last 6 months; (5) Any grade 2 or higher supraventricular or ventricular arrhythmia that requires treatment or intervention; (6) Atrial fibrillation, coronary/peripheral artery bypass grafts, or cerebrovascular symptoms including transient ischemic attacks.
• •3. Patients with factors affecting oral medication intake, such as difficulty swallowing or intestinal obstruction, or have active gastrointestinal diseases or other diseases that may significantly affect drug absorption, distribution, metabolism, or excretion (active inflammatory bowel disease or chronic diarrhea, enterocolitis or upper gastrointestinal surgery, including gastrectomy).
• •4. Patients with uncontrollable third space effusions (such as large ascites, pleural effusion, pericardial effusion) or cancerous lymphedema.
• •5. Pregnant women, nursing mothers, or those planning to become pregnant during the study period.
• •6. Patients with significant liver disease history, untreated active hepatitis B (defined as positivity for HBsAg or HBcAb and HBV-DNA levels above the normal upper limit), or active hepatitis C (defined as HCV-RNA levels above the detection limit).
• •7. Patients with uncontrolled chronic systemic comorbidities (such as severe chronic lung, liver, kidney or heart diseases).
• •8. Patients with active autoimmune diseases, history of immune deficiency, autoimmune disease history, or history of diseases or syndromes requiring systemic corticosteroid hormones or immunosuppressive drug therapy, or have acquired (HIV infection) or congenital immunodeficiency diseases, or have a history of organ transplantation (including homologous bone marrow transplantation).
• •9. Patients with active infectious tuberculosis and need for antimicrobial treatment.
• •10. Patients with known significant liver disease history, untreated active hepatitis B (defined as positivity for HBsAg or HBcAb and HBV-DNA levels above the normal upper limit), or active hepatitis C (defined as HCV-RNA levels above the detection limit).
• •11. Patients who have had other malignancies within the past 5 years, except: 1) Completely cured skin basal cell carcinoma and cervical intraepithelial neoplasia; 2) Completely cured and without recurrence of secondary primary cancer within 5 years.
• •12. Patients who have used strong or moderate inhibitors of CYP3A4 within 1 week before the first dose or strong or moderate inducers of CYP3A4 within 2 weeks before the first dose.
• •13. Pregnant women, nursing mothers, or those planning to become pregnant during the study period.
• •14. Patients with a history of neurological or psychiatric disorders, or those with a history of abuse of psychotropic drugs or drug addiction.
• •15. Patients who are expected to receive other anti-tumor treatments or medications during this study.
• •16. Patients with other serious physical or laboratory abnormalities that may increase the risk of participating in the study or interfere with study results, and those deemed by the investigator not suitable for participation in this study.
• •17. Patients with anti-tumor treatment-related toxicity in the past (excluding alopecia; according to the judgment of the investigator， after consultation with the sponsor, some tolerable chronic Grade II toxicities may be excluded).
• •18. Patients who have an allergy to any study drug or any excipient.