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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: ER-Positive, HER2-Negative Breast Cancer
• Intervention / Treatment: Drug: HRS8807; Device: HRS8807、SHR6390; Drug: HRS8807、SHR6390

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; HRS8807 monotherapy dose escalation	Drug: HRS8807; HRS8807 monotherapy
Experimental: Group B; HRS8807 monotherapy dose expansion	Drug: HRS8807; HRS8807 monotherapy
Experimental: Group C; HRS8807 in combination with SHR6390 dose escalation	Device: HRS8807、SHR6390; HRS8807 in combination with SHR6390
Experimental: Group D; HRS8807 in combination with SHR6390 dose expansion	Drug: HRS8807、SHR6390; HRS8807 in combination with SHR6390

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MTD	Maximum Tolerated Dose (MTD) of HRS8807 monotherapy and in combination with SHR6390	Change From Baseline at 28 days
RP2D	select the Recommended Phase 2 Dose (RP2D) of HRS8807 monotherapy and in combination with SHR6390	Change From Baseline at 28 days
Adverse events (AE) and serious AE (SAE)	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]).	Up to 30 days after end of treatment

Secondary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2021
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: July 20, 2021
• First Submitted That Met QC Criteria: August 5, 2021
• First Posted (Actual): August 6, 2021

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: HRS8807-I-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No