Clinical trial NCT04993430: 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
Official title: A Phase 1, Single Arm, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability and Pharmacokinetic of HRS8807 Monotherapy and in Combination With SHR6390 in Subjects With ER-Positive, HER2-Negative Metastatic or Locally Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: ER-Positive, HER2-Negative Breast Cancer
Lead sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-08-06
Enrollment: 90
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: HRS8807 monotherapy and in combination with SHR6390
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: MTD
timeFrame: Change From Baseline at 28 days
measure: RP2D
timeFrame: Change From Baseline at 28 days
measure: Adverse events (AE) and serious AE (SAE)
timeFrame: Up to 30 days after end of treatment
Secondary outcomes:
measure: Tmax of HRS8807 and the major metabolite after single dose of HRS8807
timeFrame: Day 1, Day 2, Day 3 of single dose (3 days before Cycle1)
measure: Cmax of HRS8807 and the major metabolite after single dose of HRS8807
timeFrame: Day 1, Day 2, Day 3 of single dose (3 days before Cycle1)
measure: AUC0-t of HRS8807 and the major metabolite after single dose of HRS8807
timeFrame: Day 1, Day 2, Day 3 of single dose (3 days before Cycle1)
measure: AUC0-∞ of HRS8807 and the major metabolite after single dose of HRS8807
timeFrame: Day 1, Day 2, Day 3 of single dose (3 days before Cycle1)
measure: t1/2 of HRS8807 and the major metabolite after single dose of HRS8807
timeFrame: Day 1, Day 2, Day 3 of single dose (3 days before Cycle1)
measure: Vz/F of HRS8807 and the major metabolite after single dose of HRS8807
timeFrame: Day 1, Day 2, Day 3 of single dose (3 days before Cycle1)
measure: CL/F of HRS8807 and the major metabolite after single dose of HRS8807
timeFrame: Day 1, Day 2, Day 3 of single dose (3 days before Cycle1)
measure: Tmax,ss of HRS8807 and the major metabolite after multiple dose administration of HRS8807
timeFrame: Cycle 1 Day 14, Day 15, each cycle is 28 days
measure: Cmax,ss of HRS8807 and the major metabolite after multiple dose administration of HRS8807
timeFrame: Cycle 1 Day 14, Day 15, each cycle is 28 days
measure: Cmin,ss of HRS8807 and the major metabolite after multiple dose administration of HRS8807
timeFrame: Cycle 1 Day 14, Day 15, each cycle is 28 days
measure: Rac of HRS8807 and the major metabolite after multiple dose administration of HRS8807
timeFrame: Cycle 1 Day 14, Day 15, each cycle is 28 days
measure: AUCss of HRS8807 and the major metabolite after multiple dose administration of HRS8807
timeFrame: Cycle 1 Day 14, Day 15, each cycle is 28 days
measure: Tmax of HRS8807, the major metabolite and SHR6390 after single dose administration of HRS8807 and SHR6390
timeFrame: Cycle 1 Day 1, Day 2, each cycle is 28 days
measure: Cmax of HRS8807, the major metabolite and SHR6390 after single dose administration of HRS8807 and SHR6390
timeFrame: Cycle 1 Day 1, Day 2, each cycle is 28 days
measure: AUC0-t of HRS8807, the major metabolite and SHR6390 after single dose administration of HRS8807 and SHR6390
timeFrame: Cycle 1 Day 1, Day 2, each cycle is 28 days
measure: Tmax,ss of HRS8807, the major metabolite and SHR6390 after multiple dose administration of HRS8807 and SHR6390
timeFrame: Cycle 1 Day 14, Day 15, each cycle is 28 days
measure: Cmax,ss of HRS8807, the major metabolite and SHR6390 after multiple dose administration of HRS8807 and SHR6390
timeFrame: Cycle 1 Day 14, Day 15, each cycle is 28 days
measure: Cmin,ss of HRS8807, the major metabolite and SHR6390 after multiple dose administration of HRS8807 and SHR6390
timeFrame: Cycle 1 Day 14, Day 15, each cycle is 28 days
measure: AUCss of HRS8807, the major metabolite and SHR6390 after multiple dose administration of HRS8807 and SHR6390
timeFrame: Cycle 1 Day 14, Day 15, each cycle is 28 days
measure: Rac of HRS8807, the major metabolite and SHR6390 after multiple dose administration of HRS8807 and SHR6390
timeFrame: Cycle 1 Day 14, Day 15, each cycle is 28 days
measure: Objective Response Rate (ORR)
timeFrame: baseline to the date of first documentation of progression, assessed approximately up to 6 months after the last entered participant
measure: Duration of Response (DoR)
timeFrame: baseline to the date of first documentation of progression, assessed approximately up to 6 months after the last entered participant
measure: Progression Free Survival (PFS)
timeFrame: baseline to the date of first documentation of progression, assessed approximately up to 6 months after the last entered participant
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
References: