ER-Positive, HER2-Negative Breast Cancer
Conditions
Brief summary
The study is to assess safety and tolerability of HRS8807 monotherapy and in combination with SHR6390 in subjects 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).
Interventions
DRUGHRS8807
HRS8807 monotherapy
DEVICEHRS8807、SHR6390
HRS8807 in combination with SHR6390
Sponsors
Shanghai Hengrui Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
HRS8807 monotherapy and in combination with SHR6390
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Histological diagnosis of metastatic or locally advanced breast cancer; Histologically proven diagnosis of ER-positive, HER2-negative; 2. At least 1 line of endocrine therapy in the metastatic or advanced setting that had progressed or intolerance; ≤ 2 lines of chemotherapy for metastatic or advanced disease; 3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1; 4. Expected survival of more than 3 months.
Exclusion criteria
1. All patients in monotherapy and or in combination wih phase who are known allergic to HRS8807 or SHR6390 ingredient; 2. Presence of symptomatic metastatic visceral disease ; 3. Patients with known active brain metastases; 4. Clinically serious cardiovascular disease; 5. Abnormal electrocardiographic (ECG) with clinical significancy by investigator judgement; 6. Abnormal thyroid function laboratory results; 7. Active infection or unexplained fever \>38.5℃ during screening period or on the day of the first dose.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MTD | Change From Baseline at 28 days | Maximum Tolerated Dose (MTD) of HRS8807 monotherapy and in combination with SHR6390 |
| RP2D | Change From Baseline at 28 days | select the Recommended Phase 2 Dose (RP2D) of HRS8807 monotherapy and in combination with SHR6390 |
| Adverse events (AE) and serious AE (SAE) | Up to 30 days after end of treatment | AEs and SAEs as characterized by frequency and severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE version 5.0\]). |
Secondary
| Measure | Time frame |
|---|---|
| Tmax of HRS8807 and the major metabolite after single dose of HRS8807 | Day 1, Day 2, Day 3 of single dose (3 days before Cycle1) |
| Cmax of HRS8807 and the major metabolite after single dose of HRS8807 | Day 1, Day 2, Day 3 of single dose (3 days before Cycle1) |
| AUC0-t of HRS8807 and the major metabolite after single dose of HRS8807 | Day 1, Day 2, Day 3 of single dose (3 days before Cycle1) |
| AUC0-∞ of HRS8807 and the major metabolite after single dose of HRS8807 | Day 1, Day 2, Day 3 of single dose (3 days before Cycle1) |
| t1/2 of HRS8807 and the major metabolite after single dose of HRS8807 | Day 1, Day 2, Day 3 of single dose (3 days before Cycle1) |
| Vz/F of HRS8807 and the major metabolite after single dose of HRS8807 | Day 1, Day 2, Day 3 of single dose (3 days before Cycle1) |
| CL/F of HRS8807 and the major metabolite after single dose of HRS8807 | Day 1, Day 2, Day 3 of single dose (3 days before Cycle1) |
| Tmax,ss of HRS8807 and the major metabolite after multiple dose administration of HRS8807 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| Cmax,ss of HRS8807 and the major metabolite after multiple dose administration of HRS8807 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| Cmin,ss of HRS8807 and the major metabolite after multiple dose administration of HRS8807 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| Rac of HRS8807 and the major metabolite after multiple dose administration of HRS8807 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| AUCss of HRS8807 and the major metabolite after multiple dose administration of HRS8807 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| Tmax of HRS8807, the major metabolite and SHR6390 after single dose administration of HRS8807 and SHR6390 | Cycle 1 Day 1, Day 2, each cycle is 28 days |
| Cmax of HRS8807, the major metabolite and SHR6390 after single dose administration of HRS8807 and SHR6390 | Cycle 1 Day 1, Day 2, each cycle is 28 days |
| AUC0-t of HRS8807, the major metabolite and SHR6390 after single dose administration of HRS8807 and SHR6390 | Cycle 1 Day 1, Day 2, each cycle is 28 days |
| Tmax,ss of HRS8807, the major metabolite and SHR6390 after multiple dose administration of HRS8807 and SHR6390 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| Cmax,ss of HRS8807, the major metabolite and SHR6390 after multiple dose administration of HRS8807 and SHR6390 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| Cmin,ss of HRS8807, the major metabolite and SHR6390 after multiple dose administration of HRS8807 and SHR6390 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| AUCss of HRS8807, the major metabolite and SHR6390 after multiple dose administration of HRS8807 and SHR6390 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| Rac of HRS8807, the major metabolite and SHR6390 after multiple dose administration of HRS8807 and SHR6390 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| Objective Response Rate (ORR) | baseline to the date of first documentation of progression, assessed approximately up to 6 months after the last entered participant |
| Duration of Response (DoR) | baseline to the date of first documentation of progression, assessed approximately up to 6 months after the last entered participant |
| Progression Free Survival (PFS) | baseline to the date of first documentation of progression, assessed approximately up to 6 months after the last entered participant |
Countries
China
Outcome results
None listed