Study of HRS-8080 or SHR-A2009 Combined With Anti-tumor Therapy in Patients With Unresectable or Metastatic Breast Cancer

A Multi-center, Open-label Phase Ib/II Clinical Study on the Safety, Tolerability, Pharmacokinetics and Efficacy of HRS-8080 or SHR-A2009 Combined With Anti-tumor Therapy in Patients With Unresectable or Metastatic Breast Cancer

This study is designed to determine if treatments with the combination of HRS-8080 and SHR-A1811, the combination of HRS-8080 and SHR-A2009, the combination of SHR-A2009 and SHR-1316 are safe, tolerable, and has anti-cancer activity in patients with unresectable or metastatic breast cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: HRS-8080; SHR-A1811; Drug: HRS-8080; SHR-A2009; Drug: SHR-A2009; SHR-1316

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Na An; Phone Number: +86 18500038119; Email: na.an@hengrui.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Females aged 18-75 years old (both ends inclusive);
2. ECOG performance status (PS) 0-1 points;
3. Patients with metastatic or locally advanced breast cancer confirmed by histology（ER positive, HER2 positive/negative，or triple negative breast cancer）.
4. Tumor tissue samples must be provided for detection of tumor markers;
5. Menopausal state;
6. Disease progression confirmed by imaging during or after the last systemic treatment before enrollment;
7. There must be at least one measurable extracranial lesion that complies with RECIST v1.1;
8. Expected survival >3 months;
9. Good functional level of the organs ;
10. Female subjects with childbearing potential must agree to use highly effective contraceptive measures during the study treatment period and within 7 months after the end of the study treatment period; female subjects with childbearing potential must agree to use serum serum within 7 days before study enrollment. The HCG test must be negative and the patient must be non-lactating;
11. Voluntarily participate in this clinical trial, be willing and able to comply with clinical visits and research-related procedures, understand the research procedures and have signed informed consent.

Exclusion Criteria:

1. Patients with active (without medical control or clinical symptoms) brain metastasis;
2. Have the following lung diseases or history;
3. History of clinically severe cardiovascular disease;
4. Those who have received immunosuppressants or systemic hormone therapy for immunosuppression within 2 weeks before the first dose (dose >10 mg/d prednisone or other corticosteroids at equivalent physiological doses), excluding nasal spray or inhaled hormones;
5. The damage caused by the subject receiving other treatments has not recovered (severity level NCI-CTCAE V5.0 classification ≤1, excluding hair loss and other adverse events judged to be tolerable by the researcher);
6. There are serious infections within 4 weeks before the first medication;
7. Untreated active hepatitis;
8. The subject has suffered from other malignant tumors in the past 5 years or currently, excluding cured cervical carcinoma in situ, cutaneous basal cell carcinoma and squamous cell carcinoma;
9. Presence of active autoimmune disease;
10. Have a history of immunodeficiency, including acquired (HIV infection), congenital immunodeficiency diseases, or a history of organ transplantation (including allogeneic bone marrow transplantation);
11. The subject is in the acute infection stage or active tuberculosis and requires drug treatment;
12. Known to be allergic to the components of HRS-8080, SHR-A1811 and its components, SHR-A2009 and its components, and Adebrelimab; have a history of severe allergic reactions to other monoclonal antibodies;
13. Patients who have other serious physical or mental illnesses or laboratory test abnormalities that may increase the risk of participating in the study or interfere with the results of the study, and who the researcher believes are not suitable for participation in 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A	Drug: HRS-8080; SHR-A1811; Participants will receive HRS-8080 and SHR-A1811
Experimental: Part B	Drug: HRS-8080; SHR-A2009; Participants will receive HRS-8080 and SHR-A2009
Experimental: Part C	Drug: SHR-A2009; SHR-1316; Participants will receive SHR-A2009 and SHR-1316

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limited Toxicity（DLT）	Phase 1	up to 1 cycle (21 days)
Maximum Tolerable Dose（MTD）	Phase 1	up to 1 cycle (21 days)
Recommended Phase 2 Dose（RP2D）	Phase 1	up to 1 cycle (21 days)
Safety endpoints: the incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (rated based on CTCAE V5.0)	Phase 1	up to 12 months
Efficacy endpoint: objective response rate (ORR)	Phase 2	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
level of SHR-A1811 ADA and Nab	Phase 1	up to 12 months
level of SHR-A2009 ADA and Nab	Phase 1	up to 12 months
level of adebrelimab ADA and Nab	Phase 1	up to 12 months
Objective response rate (ORR)	Phase 1	up to 12 months
Best overall response (BOR)	Phase 1	up to 12 months
Duration of response (DoR)	Phase 1	up to 12 months
Disease control rate (DCR)	Phase 1	up to 12 months
Clinical benefit rate (CBR)	Phase 1	up to 12 months
Progression-free survival (PFS)	Phase 1	up to 12 months
Safety endpoints: incidence and severity of AEs and SAEs (rated based on CTCAE V5.0)	Phase 2	up to 12 months
level of SHR-A1811 ADA and Nab	Phase 2	up to 12 months
level of SHR-A2009 ADA and Nab	Phase 2	up to 12 months
level of adebrelimab ADA and Nab	Phase 2	up to 12 months
Best overall response (BOR)	Phase 2	up to 12 months
Duration of response (DoR)	Phase 2	up to 12 months
Disease control rate (DCR)	Phase 2	up to 12 months
Clinical benefit rate (CBR)	Phase 2	up to 12 months
Progression-free survival (PFS)	Phase 2	up to 12 months

Collaborators and Investigators

• Sponsor: Shandong Suncadia Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026

Study Registration Dates

• First Submitted: December 4, 2023
• First Submitted That Met QC Criteria: January 15, 2024
• First Posted (Estimated): January 25, 2024

Study Record Updates

• Last Update Posted (Estimated): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 15, 2024
• Last Verified: January 1, 2024

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: HRS-8080-202

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