Safety and Efficacy of SPH4336 in Combination With Endocrine Therapy in the Treatment of Locally Advanced or Metastatic Breast Cancer

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 the treatment of locally advanced or metastatic breast cancer that progressed on CDK4/6 inhibitor combined with endocrine therapy.

Official Title
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A Phase II/III Study of SPH4336 in Combination With Endocrine Therapy in the Treatment of HR-positive, HER2-negative Locally Advanced or Metastatic Breast Cancer That Progressed on CDK4/6 Inhibitor Combined With Endocrine Therapy

Conditions
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Locally Advanced or Metastatic Breast Cancer

Intervention / Treatment
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* Drug: SPH4336 Tablets
* Drug: SPH4336 Tablets Placebo


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. History of other malignancies prior to the start of study treatment. Patients with known metastases to central nervous system. 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; mean QTc interval ≥ 470 ms before the start of study treatment; left ventricular ejection fraction ≤ 50% before the start of study treatment. 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 > 104 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | tumor response will be evaluated according to the Response Evaluation Criteria Solid Tumors (RECIST) criteria version 1.1. | Approximately 3years | 
| Progression-free survival (PFS) | from the start date of study treatment to the date of progression disease or death , whichever occurred first. | Approximately 3years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | PK (Pharmacokinetics) parameters | Approximately 3years | 
| Tmax | PK (Pharmacokinetics) parameters | Approximately 3years | 
| Disease control rate (DCR) | DCR was defined as the percentage of patients who have achieved complete response, partial response and stable disease | Approximately 3years | 
| Duration of remission (DOR) | DOR was defined for participants who had an objective response as the time from the first occurrence of a documented unconfirmed response to the date of disease progression per RECIST v1.1 or death from any cause | Approximately 3years | 
| Overall Survival (OS) | Determination of the overall survival times of all patients | Approximately 8years | 
| Safety and tolerability of the combination therapy since the start of any study treatment. | Adverse event type, incidence, duration, correlation with study drug | Approximately 3years |