A Phase Ib/II Study of QLC1401 Combined With CDK4/6 or mTOR Inhibitors in ER+/HER2- Advanced Breast Cancer

Inclusion Criteria:

* Voluntarily participate in the clinical trial, understand and sign the informed consent form, and agree to comply with the requirements specified in the protocol.
* Age ≥ 18 years.
* Female subjects must be postmenopausal and meet the trial requirements.
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.
* Life expectancy ≥ 3 months.
* Histologically or cytologically confirmed breast cancer.
* Based on the most recent biopsy results of primary or metastatic tumor tissue, immunohistochemistry (IHC) confirms ER-positive status and HER-2-negative status.
* At least one measurable target lesion according to RECIST v1.1.
* Adequate bone marrow function within 2 weeks (14 days) prior to the initiation of study treatment, without the need for transfusion or growth factor (G-CSF, EPO, TPO, etc.) support.
* Adequate liver function.
* Renal function: serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (Ccr) \> 30 mL/min, with no significant electrolyte imbalances that are difficult to correct.
* Coagulation function: International Normalized Ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.

Exclusion Criteria:

* Presence of symptomatic visceral disease or any other condition deemed unsuitable for endocrine therapy as per the investigator's judgment.
* Presence of unresolved toxicities from prior therapy that have not recovered to ≤ CTCAE grade 1, excluding alopecia (any grade) or other toxicities considered by the investigator to pose no safety risk.
* Received anti-tumor drug therapy within the specified time window prior to the first dose of the investigational drug.
* Prior treatment with an experimental SERD or experimental ER antagonist.
* Received radiotherapy within 4 weeks prior to the first dose of the investigational drug.
* Used a strong CYP3A4 inhibitor within 7 days or 5 half-lives (whichever is longer) prior to the first dose.
* Underwent major surgery within 4 weeks prior to the first dose of the investigational drug, or has not recovered from significant side effects, or has significant traumatic injury, non-healing wounds, or fractures.
* History of other active malignancies within 5 years prior to the first dose of the investigational drug.
* Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Inability to swallow the formulation, or gastrointestinal impairment/disease that may affect adequate absorption of the investigational drug.
* Known clinically significant liver disease, including Child-Pugh class B or C, active viral hepatitis, or other hepatitis.
* Current documented grade 1 or higher pneumonitis or interstitial lung disease.
* Clinically significant pleural effusion, ascites, or pericardial effusion, defined as detectable on examination and requiring drainage within the past 2 weeks or additional medication to control symptoms.
* Clinically significant uncontrolled cardiac disease and/or recent cardiac events.
* History of bleeding tendency, thrombosis, or tumor embolism.
* Planned treatment with everolimus and presence of uncontrolled diabetes despite adequate therapy.
* Allergy to any of the investigational medicinal products or their components.