A Clinical Trial of TQB3909 Tablets in Patients With Breast Cancer

A Phase Ib/II Study to Investigate the Safety, Tolerance and Pharmacokinetics of TQB3909 With HR-positive, HER2-negative Advanced Breast Cancer

TQB3909 is an inhibitor targeting B-cell lymphoma (BCL)-2 protein. By binding to BCL-2 protein, TQB3909 releases Pro apoptotic proteins such as BCL-2-Anatagonist/Killer 1(BAK), BCL-2 associated X (BAX) protein and BCL-2 associated death (BAD) protein, promotes the release of cytochrome c from mitochondria, phosphatidylserine eversion, stimulates caspase 3/7 activity and caspase 3/9 cleavage, and induces apoptosis.

Inclusion Criteria:

• Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.
• Age: 18 to 75 years old; female patient, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Histopathologically confirmed HR positive and HER2 negative advanced or metastatic breast cancer.
• Patients who have been treated with endocrine therapy and have experienced disease progression.
• Patients previously treated with any CDK4/6 inhibitor and not treated with BCL-2 inhibitor.
• Has at least one measurable lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria
• The main organs function well;
• Female patient had no plans to become pregnant and voluntarily took effective contraceptive measures from agree with the study to at least 6 months after the last dose of study drug.

Exclusion Criteria:

• 1. Concomitant disease and medical history:

  1. There were other malignant tumors in 3 years before the first medication.
  2. Has multiple factors affecting oral medication;
  3. Unalleviated toxicity ≥ grade 1 due to any previous therapy;
  4. Major surgical treatment, open biopsy and obvious traumatic injury were performed within 28 days before the study; e．Arteriovenous thrombotic events occurred within 6 months before the first medication, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep venous thrombosis and pulmonary embolism; f．Have a history of psychotropic drug abuse and can not quit or have mental disorders; g．Subjects with any severe and / or uncontrolled disease included: Cirrhosis, active hepatitis, history of immunodeficiency;

• Tumor-related symptoms and treatment:

  1. Has central nervous system metastases (CNS) and/or cancerous meningitis or leptomeningeal carcinomatosis;
  2. have received radiotherapy, other antineoplastic therapy within 2 weeks prior to the first dose;
  3. Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.

• Known hypersensitivity to TQB3909, LHRH agonists (e.g., goserelin), or any excipients.

• Subjects who have received the vaccine within 28 days prior to the first dose, or are planning to receive the vaccine during the study period.

• Has Participated in other clinical trials within 4 weeks before first dose.

• According to the judgement of the investigators, there are other factors that may lead to the termination of the study.