Culmerciclib Plus Anlotinib and Endocrine Therapy for HR-Positive/HER2-Negative Metastatic Breast Cancer With Brain Metastases

Prior treatment

• Prior receipt of anti-angiogenic agents or Culmerciclib
• Unresolved Grade ≥2 toxicities (per CTCAE Version 6.0) attributable to any prior therapy, except alopecia
• Participation in other anti-tumor clinical trials within 4 weeks prior to enrollment

Other illness

• Any severe and/or uncontrolled medical disease
• Other malignancies diagnosed within 5 years, excluding cured non-melanoma skin cancer, cervical carcinoma in situ and papillary thyroid carcinoma
• Radiographic evidence of tumor invasion of major vessels, or high risk of tumor invasion into major vessels resulting in life-threatening hemorrhage as assessed by the investigator
• Patients with arterial or venous thromboembolic events within 6 months, such as cerebrovascular accident, deep vein thrombosis and pulmonary embolism
• Any other condition that the investigator considers inappropriate to participate in this trial

Lab values

• Patients with visceral crisis,defined as severe organ dysfunction assessed by symptoms, signs, laboratory examinations and rapid disease progression

Other

• Patients with leptomeningeal metastases, brainstem metastases or skull metastases
• Inability to swallow capsules or tablets

• Women aged ≥ 18 years
• ECOG PS of 0-1
• Life expectancy of at least 12 weeks
• histologically or cytologically documented HR+/HER2- breast cancer
• radiologically confirmed brain parenchymal metastases without the need for immediate local therapy
• measurable brain metastasis lesion according to RANO-BM criteria
• Must have active brain metastases, defined as newly diagnosed brain metastases or progressive brain metastases following prior local therapy
• Prior systemic therapy must meet all the following criteria：
  • No more than 3 lines of prior systemic therapy for advanced disease
  • No more than 1 line of chemotherapy or antibody-drug conjugate (ADC) administered in the advanced setting
  • No prior CDK4/6 inhibitor therapy for advanced disease, or only 1 line of CDK4/6 inhibitor therapy with treatment duration \> 6 months
• Adequate hematological, hepatic and renal function
• Women of child bearing potential must agree to use a contraceptive method during the treatment period and for at least 180 days after the last dose of experiment treatment
• Patients must be able to participate and comply with treatment and follow-up