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

Evaluation of Safety, Tolerability, Efficacy, and Pharmacokinetic Characteristics of QLC1401 Tablets Combined With CDK4/6 Inhibitors or mTOR Inhibitors in Patients With Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor 2-Negative (HER2-) Locally Advanced or Metastatic Breast Cancer: A Phase Ib/II Clinical Study

This study is an open-label, multicenter, Phase Ib/II clinical trial designed to evaluate the safety, tolerability, efficacy, and pharmacokinetic characteristics of QLC1401 tablets in combination with CDK4/6 inhibitors or mTOR inhibitors in patients with ER+/HER2- locally advanced or metastatic breast cancer. The study consists of two stages: a Phase Ib dose-escalation stage and a Phase II dose-expansion stage.

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.