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

Inclusion Criteria:

* 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：

  1. No more than 3 lines of prior systemic therapy for advanced disease
  2. No more than 1 line of chemotherapy or antibody-drug conjugate (ADC) administered in the advanced setting
  3. 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

Exclusion Criteria:

* Patients with leptomeningeal metastases, brainstem metastases or skull metastases
* Prior receipt of anti-angiogenic agents or Culmerciclib
* Unresolved Grade ≥2 toxicities (per CTCAE Version 6.0) attributable to any prior therapy, except alopecia
* Patients with visceral crisis,defined as severe organ dysfunction assessed by symptoms, signs, laboratory examinations and rapid disease progression
* Inability to swallow capsules or tablets
* 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
* Participation in other anti-tumor clinical trials within 4 weeks prior to enrollment
* Any other condition that the investigator considers inappropriate to participate in this trial