A Phase 1 Study of HRS8807 Monotherapy and in Combination With SHR6390 in Subjects With ER-Positive, HER2-Negative Metastatic or Locally Advanced Breast Cancer
Phase 1
Recruiting
- Conditions
- ER-Positive, HER2-Negative Breast Cancer
- Interventions
- Drug: HRS8807、SHR6390
- Registration Number
- NCT04993430
- Lead Sponsor
- Shanghai Hengrui Pharmaceutical Co., Ltd.
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 90
Inclusion Criteria
- Histological diagnosis of metastatic or locally advanced breast cancer; Histologically proven diagnosis of ER-positive, HER2-negative;
- 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;
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1;
- Expected survival of more than 3 months.
Exclusion Criteria
- All patients in monotherapy and or in combination wih phase who are known allergic to HRS8807 or SHR6390 ingredient;
- Presence of symptomatic metastatic visceral disease ;
- Patients with known active brain metastases;
- Clinically serious cardiovascular disease;
- Abnormal electrocardiographic (ECG) with clinical significancy by investigator judgement;
- Abnormal thyroid function laboratory results;
- Active infection or unexplained fever >38.5℃ during screening period or on the day of the first dose.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Group A HRS8807 HRS8807 monotherapy dose escalation Group B HRS8807 HRS8807 monotherapy dose expansion Group C HRS8807、SHR6390 HRS8807 in combination with SHR6390 dose escalation Group D HRS8807、SHR6390 HRS8807 in combination with SHR6390 dose expansion
- Primary Outcome Measures
Name Time Method MTD Change From Baseline at 28 days Maximum Tolerated Dose (MTD) 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 \[NCI CTCAE version 5.0\]).
RP2D Change From Baseline at 28 days select the Recommended Phase 2 Dose (RP2D) of HRS8807 monotherapy and in combination with SHR6390
- Secondary Outcome Measures
Name Time Method 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-∞ 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) 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 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 Rac 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, the major metabolite and SHR6390 after multiple dose administration of HRS8807 and SHR6390 Cycle 1 Day 14, Day 15, each cycle is 28 days 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) 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) 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 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 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 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 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 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)
Trial Locations
- Locations (1)
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China