A Phase Ib/II Study of QLC1401 Combined With CDK4/6 or mTOR Inhibitors in ER+/HER2- Advanced Breast Cancer
Not Applicable
Not yet recruiting
- Conditions
- Advanced Breast Cancer
- Interventions
- Drug: QLC1401
- Registration Number
- NCT07173556
- Lead Sponsor
- Qilu Pharmaceutical Co., Ltd.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 96
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description QLC1401 in combination with CDK4/6 inhibitors QLC1401 - QLC1401 in combination with mTOR inhibitors QLC1401 -
- Primary Outcome Measures
Name Time Method Safety and Tolerability (Phase Ib) Throughout phase Ib (approximately 1 year) Types, incidence, and severity grades of AEs/SAEs and safety abnormalities, and their relationship to the investigational product; proportion of patients requiring dose adjustments or treatment discontinuation due to drug-related AEs.
Recommended phase II dose (RP2D) (Phase Ib) Throughout phase Ib (approximately 1 year) RP2D will be selected upon safety, PK and efficacy data.
Objective Response Rate (ORR) (Phase II) From time of Informed Consent to confirmed progressive disease (approximately 1 year) Objective Response Rate (ORR) as assessed by investigators per RECIST v1.1 criteria
- Secondary Outcome Measures
Name Time Method