A Trial of HRS-6209 in Combination With Fulvestrant, Letrozole, HRS-8080, or HRS-1358 in Breast Cancer Patients

An Open-Label, Multi-Center Phase Ib/II Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HRS-6209 in Combination With Fulvestrant, Letrozole, HRS-8080, or HRS-1358 in Patients With Advanced Unresectable or Metastatic Breast Cancer

The study is being conducted to evaluate the safety, PK and efficacy of HRS-6209 in Combination with Fulvestrant, Letrozole, HRS-8080, or HRS-1358 for advanced unresectable or metastatic breast cancer

Study Overview

• Status: Recruiting
• Conditions: Advanced Unresectable or Metastatic Breast Cancer
• Intervention / Treatment: Drug: HRS-6209 in Combination with Fulvestrant; Drug: HRS-6209 in Combination with HRS-1358; Drug: HRS-6209 in Combination with Letrozole; Drug: HRS-6209 in Combination with HRS-8080; Drug: HRS-6209 in Combination with HRS-9813 and Letrozole; Drug: HRS-6209 in Combination with HRS-9813 and HRS-8080

• Study Type: Interventional
• Enrollment (Estimated): 528
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xiaonan Sheng; Phone Number: +86 13524857678; Email: xiaonan.sheng.xs6@hengrui.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Principal Investigator: Jiong Wu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Females aged 18-75 years (inclusive);
2. ECOG performance status (PS) score of 0-1;
3. Patients with histopathologically confirmed metastatic or unresectable locally advanced breast cancer;
4. Patients with advanced malignant solid tumors confirmed by histopathology or cytopathology, who have failed standard treatment, or for whom no effective standard treatment regimen is available, or who are unable to receive further standard treatment.

5. Menopausal status:

   1. Having had bilateral oophorectomy, or aged ≥ 60 years old; or
   2. Aged < 60, natural menopause (defined as spontaneous cessation of regular menses for at least 12 consecutive months in the absence of other pathological or physiological causes) with E2 and FSH at postmenopausal levels; or
   3. Premenopausal or perimenopausal patients, agree to start or continue receive LHRH agonists during the study (exclude from the QT/QTc group).
6. Disease progression evidenced by imaging during or after the last systemic anti-tumor treatment prior to the first dose (limited to the efficacy expansion stage);
7. With at least one extracranial measurable target lesion at baseline per RECIST v1.1;
8. Life expectancy of > 3 months;
9. Adequate organ and marrow function as defined by the protocol;Female subjects of childbearing potential should agree to adopt effective contraceptive measures during the study period and within 7months after the end of the study treatment; female subjects of childbearing potential must have a negative serum HCG test result within 7 days before enrollment in the study and must not be in the lactation;
10. Voluntarily participate in this clinical study, be willing and able to comply with procedures related to clinical visits and study, and understand and have signed written informed consent.

Exclusion Criteria:

1. With symptomatic visceral metastases deemed unfit for endocrine therapy by the investigator;
2. With active brain metastases, carcinomatous meningitis, spinal cord compression, or a history of primary tumors of the central nervous system;
3. History of clinically significant cardiovascular disease, including;
4. Abnormal ECG findings, which are judged by the investigator to be clinically significant and and need to intervene;
5. Previous use of fulvestrant for cohort of HRS-6209 in combination with fulvestrant (efficacy expansion stage).
6. With factors that affect oral medication, active gastrointestinal diseases, or other diseases that may obviously affect drug absorption, distribution, metabolism, or excretion;
7. With clinically significant endometrial abnormalities, including but not limited to endometrial hyperplasia and dysfunctional uterine bleeding;
8. Active infection or unexplained fever > 38.5 °C during the screening period or on the day of first dose;
9. With uncontrollable chronic systemic complications as judged by the investigator.
10. With active autoimmune diseases, history of immunodeficiency and history of autoimmune diseases, history of diseases or syndromes that require systemic corticosteroids or immunosuppressive drugs, other acquired (HIV infection) or congenital immunodeficiency, or history of organ transplantation (including allogeneic bone marrow transplantation);
11. With acute infection or active tuberculosis requiring medication.
12. With a known history of clinically significant liver disease, untreated active hepatitis;
13. Had other concurrent malignant tumors in the past 5 years, except: 1. Cervical carcinoma in situ that has been cured, 2. Second primary cancer that has been cured without recurrence within five years;
14. Use of moderate and strong CYP3A4 inhibitors within 1 week or moderate and strong CYP3A4 inducers within 2 weeks prior to the first dose;
15. Use of any drugs with the risk of prolonging QT/QTc interval or causing torsade de pointes (TdP) within 4 weeks prior to the first dose, and with previous congenital QT interval prolongation syndrome or a family history of QT interval prolongation, implanted pacemakers or automatic implantable cardioverter defibrillators, uncorrectable electrolyte disorders, and other factors that may affect the QT/QTc study;
16. Surgical treatment (except for needle biopsy or PICC catheterization or PORT catheterization), chemotherapy (except for 5-Fu drugs), immunotherapy, macromolecular targeted therapy, etc. within 4 weeks before the first dose; Received endocrine therapy, 5-FU chemotherapy or radiotherapy within 2 weeks before the first dose; Small molecule targeted drugs need to be washed out for 2 weeks or 5 half-lives (whichever is longer);
17. Pregnant or lactating women, or females planning to become pregnant during the study period;
18. With clear history of neural or mental disorders or with history of psychotropic abuse or drug abuse;

20) Subjects who are expected to receive other anti-tumor therapies or drugs during this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group A: HRS-6209 in Combination with Fulvestrant	Drug: HRS-6209 in Combination with Fulvestrant; HRS-6209 in Combination with Fulvestrant
Experimental: Treatment group E: HRS-6209 in Combination with HRS-1358	Drug: HRS-6209 in Combination with HRS-1358; HRS-6209 in Combination with HRS-1358
Experimental: Treatment group B：HRS-6209 in Combination with Letrozole	Drug: HRS-6209 in Combination with Letrozole; HRS-6209 in Combination with Letrozole
Experimental: Treatment group C：HRS-6209 in Combination with HRS-8080	Drug: HRS-6209 in Combination with HRS-8080; HRS-6209 in Combination with HRS-8080
Experimental: Treatment group D：HRS-6209 in Combination with HRS-8080	Drug: HRS-6209 in Combination with HRS-8080; HRS-6209 in Combination with HRS-8080
Experimental: Treatment group F: HRS-6209 in Combination with HRS-1358	Drug: HRS-6209 in Combination with HRS-1358; HRS-6209 in Combination with HRS-1358
Experimental: Treatment group G：HRS-6209 in Combination with HRS-9813 and Letrozole	Drug: HRS-6209 in Combination with HRS-9813 and Letrozole; HRS-6209 in Combination with HRS-9813 and Letrozole
Experimental: Treatment group H：HRS-6209 in Combination with HRS-9813 and HRS-8080	Drug: HRS-6209 in Combination with HRS-9813 and HRS-8080; HRS-6209 in Combination with HRS-9813 and HRS-8080
Experimental: Treatment group I：HRS-6209 in Combination with HRS-9813 and HRS-8080	Drug: HRS-6209 in Combination with HRS-9813 and HRS-8080; HRS-6209 in Combination with HRS-9813 and HRS-8080

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
DLT (dose-limiting toxicity)-Stage I (dose exploration)	28 days after the first dose
MTD (maximum tolerated dose) -Stage I (dose exploration)	28 days after the first dose
RP2D (recommended phase II dose) -Stage I (dose exploration)	28 days after the first dose
(Serious) AEs-Stage I (dose exploration)	every week in Cycle 1 (28 days after the first dose), every 2 weeks in Cycle 2 (28 days after the second dose), every 4 weeks from Cycle 3 and thereafter (28 days after each dose), lasting about one year
ORR ( objective response rate )-Stage II (efficacy expansion)	every 8 weeks lasting about one year

Secondary Outcome Measures

Outcome Measure	Time Frame
ORR (objective response rate) (Stage I)	every 8 weeks lasting about one year
BOR (best overall response) (Stage I)	every 8 weeks lasting about one year
DoR (duration of response) (Stage I)	every 8 weeks lasting about one year
CBR (clinical benefit rate) (Stage I)	every 8 weeks lasting about one year
PFS (progression-free survival) (Stage I)	every 8 weeks lasting about one year
(Serious) AEs (Stage II)	every week in Cycle 1 (28 days after the first dose), every 2 weeks in Cycle 2 (28 days after the second dose), every 4 weeks from Cycle 3 and thereafter (28 days after each dose), lasting about one year
BOR (best overall response) (Stage II)	every 8 weeks lasting about one year
DoR (duration of response) (Stage II)	every 8 weeks lasting about one year
CBR (clinical benefit rate) (Stage II)	every 8 weeks lasting about one year
PFS (progression-free survival) (Stage II)	every 8 weeks lasting about one year
Cmax, ss (Stage I)	Cycle 1 (each cycle is 28 days) day 15、Cycle 2 (each cycle is 28 days) 、 Cycle 3 (each cycle is 28 days)、Cycle 4 (each cycle is 28 days)、、Cycle 5 (each cycle is 28 days)、Cycle 6 (each cycle is 28 days)
Tmax, ss (Stage I)	Cycle 1 (each cycle is 28 days) day 15、Cycle 2 (each cycle is 28 days) 、 Cycle 3 (each cycle is 28 days)、Cycle 4 (each cycle is 28 days)、、Cycle 5 (each cycle is 28 days)、Cycle 6 (each cycle is 28 days)
Cmin, ss(Stage I)	Cycle 1 (each cycle is 28 days) day 15、Cycle 2 (each cycle is 28 days) 、 Cycle 3 (each cycle is 28 days)、Cycle 4 (each cycle is 28 days)、、Cycle 5 (each cycle is 28 days)、Cycle 6 (each cycle is 28 days)
AUCss (Stage I)	Cycle 1 (each cycle is 28 days) day 15、Cycle 2 (each cycle is 28 days) 、 Cycle 3 (each cycle is 28 days)、Cycle 4 (each cycle is 28 days)、、Cycle 5 (each cycle is 28 days)、Cycle 6 (each cycle is 28 days)
Cmax, ss (Stage II)	Cycle 1 (each cycle is 28 days) day 15、Cycle 2 (each cycle is 28 days) 、 Cycle 3 (each cycle is 28 days) 、Cycle 4 (each cycle is 28 days)、、Cycle 5 (each cycle is 28 days)、Cycle 6 (each cycle is 28 days)
Tmax, ss (Stage II)	Cycle 1 (each cycle is 28 days) day 15、Cycle 2 (each cycle is 28 days) 、 Cycle 3 (each cycle is 28 days) 、Cycle 4 (each cycle is 28 days)、、Cycle 5 (each cycle is 28 days)、Cycle 6 (each cycle is 28 days)
Cmin, ss(Stage II)	Cycle 1 (each cycle is 28 days) day 15、Cycle 2 (each cycle is 28 days) 、 Cycle 3 (each cycle is 28 days) 、Cycle 4 (each cycle is 28 days)、、Cycle 5 (each cycle is 28 days)、Cycle 6 (each cycle is 28 days)
AUCss (Stage II)	Cycle 1 (each cycle is 28 days) day 15、Cycle 2 (each cycle is 28 days) 、 Cycle 3 (each cycle is 28 days) 、Cycle 4 (each cycle is 28 days)、、Cycle 5 (each cycle is 28 days)、Cycle 6 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: August 1, 2024
• First Submitted That Met QC Criteria: August 12, 2024
• First Posted (Actual): August 15, 2024

Study Record Updates

• Last Update Posted (Actual): July 16, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Nitriles; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Triazoles; Letrozole; Fulvestrant
• Other Study ID Numbers: HRS-6209-201

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