Clinical Trial of Evaluating TQB3912 Tablets Combined With Fulvestrant Injection±TQB3616 Capsules for Locally Advanced or Metastatic Hormone Receptor(HR)-Positive and Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer

• The subjects voluntarily joined the study, signed an informed consent form, and had good compliance.
• Age: 18-75 years old; Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score: 0\~1 point; estimated survival time exceeds 3 months.
• Women can be in the late period of menopause and before menopause/innerspring. If they are before menopause/siege period, they must continue to receive ovarian function inhibitory treatment during the research period to enter the group.
• Anthropologically confirmed HR-positive and HER2-negative breast cancer.
• Locally advanced or metastatic diseases that cannot undergo radical surgery.
• Queue 1 Previous treatment requirements: progress after endocrine therapy; Queue 2 Previous treatment requirements: progress after endocrine therapy.
• Have one or more phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA)/v-akt murine thymoma viral oncogene homolog 1 (AKT1)/phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene mutations.
• At least one measurable lesion exists according to the RECIST 1.1 standard.
• Good function of the main organs
• Female subjects of childbearing age should agree that contraceptive measures (such as Buds, contraceptives or condoms) must be used during the study period and within 6 months after the study ends; the serum pregnancy test is negative within 7 days before the study enrollment. , and must be non-lactation subjects; male subjects should agree to adopt contraceptive measures within 6 months after the end of the study period.

Exclusion Criteria:

• It is known to suffer from spinal cord compression, cancerous meningitis, symptoms with brain metastasis or symptoms control for less than 4 weeks.

• Combined diseases and medical history:

  1. Have appeared within 3 years or have also suffered from other malignant tumors;
  2. Adverse reactions from previous treatments have not been restored to CTCAE 5.0 grade≤1;
  3. It affects oral and drug absorption
  4. Those who have received major surgical treatment within 4 weeks before the first medication, obvious traumatic injury or expected to undergo major surgery during the study treatment, or have long-term uncured wounds or fractures;
  5. Congenital bleeding , coagulation dysfunction disease;
  6. Arterial/deep thrombosis events occurred;
  7. Blood pressure control was not ideal;
  8. Major cardiovascular disease;
  9. Uncontrolled ≥CTCAE level 2 within 14 days before the start of study treatment
  10. A history of active tuberculosis, pulmonary fibrosis or pneumonia;
  11. a past or currently associated with interstitial lung disease/pneumonia;
  12. active viral hepatitis and poor control;
  13. treatment is required
  14. uncontrollable kidney disease;
  15. a history of immunodeficiency;
  16. a person who is prepared to undergo or has undergone genealogical bone marrow transplants or solid organ transplants;
  17. uncontrollable diabetes;
  18. a person who suffers from People with epilepsy and need treatment;
  19. People with a history of psychotropic substance abuse and cannot be abstained or have mental disorders.

• Tumor-related symptoms and treatment:

  1. If it is not controlled, the third gap effusion still needs to be repeatedly drained;
  2. There is lung cancer pharyngitis;
  3. During the study period, the tumor is very likely to invade important blood vessels and cause it Fatal severe bleeding;
  4. Use strong CYP3A4 inhibitor or strong inducer, and the drug half-life is less than 3 before the start of the study treatment;
  5. Have received anti-tumor treatment within 3 weeks before the start of the study treatment, and the washing is calculated from the end of the last treatment
  6. Within 2 weeks before the start of the study treatment, Chinese patent medicine treatment with anti-tumor indications was received in the National Medical Products Administration (NMPA) approved drug instructions.

• Research and treatment related:

  1. Used phosphatidylinositol 3 kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) inhibitors;
  2. Used fulvestrant or other selective estrogen receptor degrading agents (SERD);
  3. Used in any study drug or drug Allergic to any ingredient or excipient;
  4. a history of live attenuated vaccination within 28 days before the first medication or planned to undergo live attenuated vaccination during the study period;
  5. is receiving systemic glucocorticoid therapy or any other form of immunosuppression therapy, and Continued use within 2 weeks before the start of the study treatment
• According to the judgment of the researcher, there are situations that seriously endanger the safety of the subject or affect the subject's completion of the research.