A Trial of HRS-1358 Tablets in Metastatic or Local Advanced Breast Cancer

Study Overview
=================
Brief Summary
-----------------
The study is being conducted to evaluate the safety and tolerability of HRS-1358 monotherapy in patients with metastatic or locally advanced breast cancer in order to estimate the Dose-Limiting Toxicity (DLT), Maximum Tolerated Dose (MTD) and select the Recommended Phase 2 Dose (RP2D).

Official Title
-----------------
A Single-arm, Open-label, Multi-center Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HRS-1358 Monotherapy in Patients With Metastatic or Locally Advanced Breast Cancer.

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: HRS-1358


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically diagnosis of local advanced or metastatic breast cancer Women must be postmenopausal, or pre-/peri-menopausal women must be on ovarian suppression At least 1 line of endocrine therapy in the metastatic or advanced setting ECOG performance status score: 0-1; Adequate organ functions as defined Ability to understand and voluntarily agrees to participate by giving written informed consent for the study. Exclusion Criteria: the investigators judged that it was not suitable to endocrine therapy patients with active brain metastasis (without medical control or with clinical symptoms), History of clinically significant cardiovascular or cerebrovascular diseases The subject has one of many factors affecting oral 、absorption, distribution, metabolism and excretion of drugs Active autoimmune diseases, History of immunodeficiency, including positive HIV serum test result and other acquired or congenital immunodeficiency diseases, or history of organ transplantation Have received other similar drugs in the past; Known history of allergy to HRS-1358 ingredients

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

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single arm study of HRS-1358
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HRS-1358<br>Daily oral dosages of HR-1358 | Drug: HRS-1358<br>* HRS-1358 will be administered daily orally in continuous dosing over 28-day cycles.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limited Toxicities (DLTs) | Number of participants with dose-limiting toxicities (DLTs) | up to 28 days | 
| Maximum tolerated dose | The Maximum tolerated dose of HRS-1358 monotherapy | up to 28 days | 
| RP2D | select the Recommended Phase 2 Dose (RP2D) of HRS-1358 | Change From Baseline at 28 days | 
| Incidence and severity of adverse events (AEs)/serious adverse events (SAEs) | Incidence and severity of adverse events (AEs)/serious adverse events (SAEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | up to 30 days after the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | PK parameters of multiple doses of HRS-1358 monotherapy | 0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period | 
| Tmax | PK parameters of multiple doses of HRS-1358 monotherapy | 0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period | 
| AUC0-t | PK parameters of multiple doses of HRS-1358 monotherapy | 0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period | 
| Cmax,ss | PK parameters of multiple doses of HRS-1358 monotherapy | 0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period | 
| Tmax,ss | PK parameters of multiple doses of HRS-1358 monotherapy | 0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period | 
| Cmin,ss | PK parameters of multiple doses of HRS-1358 monotherapy | 0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period | 
| AUCss | PK parameters of multiple doses of HRS-1358 monotherapy | 0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period | 
| Rac | PK parameters of multiple doses of HRS-1358 monotherapy | 0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period | 
| Overall response rate (ORR) in participants |  | Up to approximately 1 year | 
| Clinical benefit rate (CBR) in participants |  | Up to approximately 1 year | 
| Duration of response (DOR) in participants |  | Up to approximately 1 year | 
| Progression Free Survival (PFS) observed in participants |  | Up to approximately 1 year |