An Investigator-initiated Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Sirolimus（Albumin-bound）in Combination With Palbociclib and Fulvestrant in Patients With Advanced HR- Positive, HER2- Negative Breast Cancer
This study adopts a single-center, open-label, non-randomized trial design. It plans to enroll patients with HR- positive, HER2- negative advanced breast cancer who are resistant to (neo)adjuvant endocrine therapy. Dose-escalation and dose-expansion studies will be carried out to evaluate the safety, tolerability, and preliminary efficacy of sirolimus (albumin-bound) in combination with palbociclib and fulvestrant in this patient population, and to confirm the recommended phase 2 dose (RP2D)
• 1\. Subjects should be over 18 years old, regardless of gender. Among them, female patients should be post - menopausal status
• 2\. Histologically or cytologically confirmed HR - positive, HER2 - negative advanced breast cancer.
• 3\. The investigator assesses that the patient is suitable for palbociclib and fulvestrant treatment at the current stage.
• 4\. There is at least one measurable lesion that meets the RECIST V1.1 criteria (only applicable to the dose - expansion stage)
• 5\. The Eastern Cooperative Oncology Group (ECOG) performance status score is 0 - 1.
• 6\. For patients in the dose - escalation stage, there are no restrictions on previous treatments. The investigator needs to determine that the patient is suitable for enrollment in the study and receiving the investigational drugs at the current stage. For patients in the dose - expansion stage, the following criteria must be met:
• The patient has received (neo)adjuvant endocrine therapy (either as a single agent or in combination). There should be imaging evidence of breast cancer recurrence or progression during or within 12 months after the completion of (neo)adjuvant endocrine therapy (tamoxifen, AI, or oral SERD).
• Patients in the recurrent or metastatic stage have not received systemic chemotherapy. (Note 1: A chemotherapy regimen that is terminated due to toxicity during the first cycle or after the completion of treatment, and there is no clinical or imaging evidence of disease progression at the start of subsequent treatment, is not counted as a line of treatment. Note 2: Adjuvant and neoadjuvant chemotherapy are not classified as lines of treatment for ABC. Note 3: Antibody - drug conjugates are classified as chemotherapy)
• Patients in the recurrent or metastatic stage have not received CDK4/6 inhibitor treatment. (Note 1: It is allowed that the patient has received CDK4/6i during (neo)adjuvant therapy, and there is a disease - free interval of at least 12 months (i.e., at least 12 months between the last day of CDK4/6i treatment and the date of recurrence). In addition, drug replacement in patients without disease progression does not count as a new line of treatment)