Efficacy and Safety of SPH4336 in Combination With Endocrine Therapy in Breast Cancer Patients With Brain Metastases.

Study Overview
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Brief Summary
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This study evaluated the safety and efficacy of SPH4336 in combination with endocrine therapy in breast cancer Patients with brain metastases.

Official Title
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A Phase II Study of SPH4336 in Combination With Endocrine Therapy in HR-positive, HER2-negative Breast Cancer Patients With Brain Metastases.

Conditions
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Breast Cancer Brain Metastases

Intervention / Treatment
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* Drug: SPH4336 Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who voluntarily participate in this study, completely understand this study, and voluntarily sign the informed consent form (ICF). ECOG (Eastern Cooperative Oncology Group) performance status score of 0 or 1. Life expectancy ≥ 3 months. Patients with locally advanced or metastatic breast cancer who are unable to receive radical surgeries/other local therapies. At least one measurable lesion . Laboratory test results meet the relevant requirements for organ function. Subjects who agree to take effective contraceptive measures. Exclusion Criteria: Inflammatory breast cancer. Patients unsuitable for endocrine therapy at the investigator's discretion. Have a History of other malignancies prior to the start of study treatment. Taking anti-tumor traditional Chinese patent medicines at the time of signing the ICF. Patients who underwent a surgery prior to the start of study treatment, and have not yet recovered from adverse reactions of the surgery. Patients who participated in a clinical trial and received other investigational drugs before the start of study treatment. Pregnant or lactating women. History of myocardial infarction, unstable angina pectoris, severe arrhythmia, and symptomatic congestive heart failure before the start of study treatment; ≥ NYHA (New York Heart Association) Class II; QTcF≥ 470 ms; left ventricular ejection fraction ≤ 50%. History of ischemic stroke or severe thromboembolic disease before the start of study treatment. Hepatitis B surface antigen positive and HBV (Hepatitis B Virus) DNA > 2,000 IU/mL or > 10(4) copies/mL; HCV (Hepatitis C Virus) antibody positive and HCV RNA positive; or known HIV infection. History of severe allergic diseases, history of severe drug allergies, or known allergy to any ingredient of the investigational product. Presence of diseases or conditions that may impact drug administration or gastrointestinal absorption before the start of study treatment. Presence of uncontrolled infections before the start of study treatment. Known history of drug abuse, excessive drinking, or illegal drug use; history of confirmed neurological or mental disorders. Presence of other diseases that the risks of receiving the study treatment outweigh its benefits, as determined by the investigator, or any other reason for which patients are ineligible for the study as assessed by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPH4336 Tablets<br>SPH4336 Tablets; Letrozole tablets; Fulvestrant; Exemestane | Drug: SPH4336 Tablets<br>* SPH4336 Tablets ：Administered by oral; Letrozole tablets：Administered by oral; Fulvestrant injection：Administered by intravenous infusion; Exemestane：Administered by oral.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intracranial Objective response rate（iORR） | Objective response rate according to response assessment in neuro-oncology-brain metastases (RANO-BM) criteria. | Approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intracranial Duration of remission (iDOR) | DoR is measured from the date of first evidence of a confirmed response (CR or PR), as defined by RANO-BM, to the date objective progression or death from any cause. | Approximately 3 years | 
| Intracranial Disease control rate (iDCR) | Percentage of participants with BOIR of CR, PR, or SD: IDCR, as defined by RANO-BM is reported. | Approximately 3 years | 
| Progression-free survival (PFS) | measured by RANO-BM and RECIST 1.1 | Approximately 3 years | 
| Overall Survival (OS) | Determination of the overall survival times of all patients. | Approximately 8 years | 
| Extracranial Objective response rate（eORR） | Objective response rate according to response assessment in neuro-oncology-brain metastases (RANO-BM) criteria. | Approximately 3 years | 
| Extracranial Disease control rate (eDCR) | Percentage of participants with BOIR of CR, PR, or SD: IDCR, as defined by RANO-BM is reported. | Approximately 3 years | 
| Extracranial Duration of remission (eDOR) | DoR is measured from the date of first evidence of a confirmed response (CR or PR), as defined by RANO-BM, to the date objective progression or death from any cause. | Approximately 3 years | 
| Cmax | PK (Pharmacokinetics) parameters | Approximately 3 years | 
| Tmax | PK (Pharmacokinetics) parameters | Approximately 3 years | 
| Safety and tolerability | Adverse event type, incidence, correlation with study drug | Approximately 3 years |