Advanced Breast Cancer
Conditions
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.
Interventions
DRUGQLC1401
CDK4/6 inhibitors: Palbociclib, Abemaciclib, Ribociclib
Sponsors
Qilu Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Contacts
Primary ContactZhimin Shao, MD
Backup ContactJian Zhang, MD
Outcome results
None listed