A Study of SHR-A1811 and Fulvestrant, With or Without HS-10352, in Locally Advanced or Metastatic Breast Cancer Patients

A Phase Ib/II Study of SHR-A1811 and Fulvestrant in Combination With or Without HS-10352 in Locally Advanced or Metastatic Breast Cancer Patients Who Progressed After Adjuvant Therapy

This study is being conducted to evaluate the efficacy and safety of SHR-A1811 and Fulvestrant in Combination with or without HS-10352 in locally advanced or metastatic breast cancer patients. Subjects will receive SHR-A1811 and Fulvestrant in Combination with or without HS-10352.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer; Locally Advanced or Metastatic Breast Cancer
• Intervention / Treatment: Drug: SHR-A1811+ Fulvestrant; Drug: SHR-A1811+ Fulvestrant+HS-10352

Detailed Description

This study plans to enroll breast cancer patients whose disease progressed during treatment or within 12 months of completing adjuvant therapy and who have not received prior systemic therapy. SHR-A1811 + fulvestrant group will receive treatment with SHR-A1811 and fulvestrant. HS-10352 group will receive treatment with SHR-A1811, fulvestrant, and HS-10352. Treatment will continue until disease progression or the occurrence of intolerable toxicity.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Zhenzhen Liu, MD; Phone Number: 86-13603862755; Email: liuzhenzhen73@126.com
• Study Contact Backup: Name: Xiaosan Zhang, MD; Phone Number: 86-15638167115; Email: zxs_8112@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Female patients aged ≥18 years and ≤75 years;
2. ECOG Performance Status of 0 -2;
3. Locally advanced/metastatic breast cancer not amenable to curative therapy
4. Disease progression during treatment or within 12 months of completing adjuvant therapy ;
5. No prior anti-cancer systemic therapy has been administered;
6. Fasting blood glucose < 126 mg/dL, and HbA1C < 6.0%;
7. Life expectancy of ≥3 months;
8. Patients have at least one target lesion according to RECEST 1.1;
9. Adequate function of major organs;
10. Female patients who are either premenopausal or have not undergone surgical sterilization: during the treatment period and for at least 7 months after the final dose of study medication, agree to abstain from sexual activity or utilize effective contraceptive methods.
11. Sign Informed Consent Form.

Exclusion Criteria:

1. Breast cancer that has not been histologically confirmed;
2. Inflammatory breast cancer;
3. Participants ineligible for endocrine therapy due to any disease burden, as judged by the investigator;
4. Meningeal metastasis or active parenchymal brain metastasis;
5. Presence of diabetes symptoms, history of primary diabetes, gestational diabetes, steroid-induced diabetes, or other secondary diabetes;
6. Prior anti-cancer systemic therapy has been administered;
7. Use of investigational drugs within 4 weeks；
8. Received immunotherapy, macromolecular targeted therapy, or other antitumor biologics within 4 weeks; or received endocrine therapy, chemotherapy, small molecule targeted drug therapy, or traditional Chinese medicine treatment with antitumor indications within 2 weeks;
9. Received radical radiotherapy within 4 weeks, or received palliative radiotherapy within 2 weeks;
10. Previously received antitumor treatment or radiotherapy for any malignancy, excluding malignancies such as cured cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma;
11. A history of other malignancies within the past 5 years, excluding cured cases of skin basal cell carcinoma and cervical carcinoma in situ;
12. Prior anti-tumor treatment toxicities have not yet recovered to NCI CTCAE V5.0 grade ≤1 or baseline levels;
13. A history of immunodeficiency, including HIV positivity, other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
14. Interstitial pneumonia/interstitial lung disease, or presence of moderate to severe pulmonary disease that may interfere with the detection or management of drug-related pulmonary toxicity within 3 months prior to the first administration of the study drug, as well as any autoimmune, connective tissue, or inflammatory diseases involving the lungs, or a history of total pulmonary resection surgery
15. Presence of active hepatitis B, hepatitis C, liver cirrhosis, or severe infections requiring control with antibiotics, antiviral drugs, or antifungal medications;
16. History of hereditary or acquired bleeding and thrombotic tendencies (such as haemophilia, coagulation disorders, etc.);
17. Inability to swallow, intestinal obstruction, or the presence of other factors affecting drug intake and absorption;
18. Patients with known allergies or contraindications to the study drug and its excipient components;
19. Female patients who are pregnant or lactating, those of reproductive potential with a positive baseline pregnancy test, or those of reproductive age who are unwilling to use effective contraceptive measures throughout the entire study period;
20. According to the investigator's judgment, patients with severe concomitant diseases that pose a risk to their safety or prevent them from completing the study, a history of definite neurological or psychiatric disorders, including epilepsy or dementia, or any other condition deemed by the investigator to make the patient unsuitable for participation in this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR-A1811 + fulvestrant group; Subjects will receive SHR-A1811 combined with fulvestrant therapy.	Drug: SHR-A1811+ Fulvestrant; SHR-A1811 is administered intravenously; fulvestrant is administered Intramuscular
Experimental: HS-10352 group; Subjects will receive SHR-A1811 combined with Fulvestrant and HS-10352 therapy.	Drug: SHR-A1811+ Fulvestrant+HS-10352; SHR-A1811 is administered intravenously; fulvestrant is administered Intramuscular ； HS-10351 is administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) according to RECIST1.1 （SHR-A1811+fulvestrant group and HS-10352 group (Phase II)）	ORR defined as the proportion of patients with the best overall response of complete response or partial response，as determined by the investigator according to RECIST v1.1	Up to approximately 4 years
Recommended Phase 2 dose (RP2D) (HS-10352 group (Phase Ib))		From the first dose to the last dose of the first cycle defined as 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) （SHR-A1811 + fulvestrant group and HS-10352 group (Phase II)）	Evaluate the incidence and severity of adverse events according to CTCAE 5.0	Up to approximately 4 years
Objective Response Rate (ORR) according to RECIST1.1 （HS-10352 group(Phase Ib)）	ORR defined as the proportion of patients with the best overall response of complete response or partial response，as determined by the investigator according to RECIST v1.1	Up to approximately 4 years
Progression-Free Survival (PFS)（SHR-A1811 +fulvestrant group and HS-10352 group (Phase Ib/Phase II)）	PFS is defined as the time from the first therapeutic dose to death or disease progression	Up to 4 years
Overall Survival (OS) （SHR-A1811 +fulvestrant group and HS-10352 group (Phase Ib/Phase II)）	OS is defined as the time from the first therapeutic dose to death from any cause	Up to 4 years
Clinical Benefit Rate (CBR) （CR+ PR+ SD≥24weeks）（SHR-A1811 +fulvestrant group and HS-10352 group (Phase Ib/Phase II)）	CBR is defined as the percentage of participants with a CR, PR, and/or stable disease (SD) for at least 24 weeks, as determined by the investigator according to RECIST v1.1	Up to 4 years
Duration of Response (DOR) （SHR-A1811 +fulvestrant group and HS-10352 group (Phase Ib/Phase II)）	DOR is defined as the time from the first occurrence of a CR or PR to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first)	Up to 4 years

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital
• Investigators: Principal Investigator: Zhenzhen Liu, MD, Henan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2029

Study Registration Dates

• First Submitted: January 21, 2025
• First Submitted That Met QC Criteria: January 21, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 26, 2025
• Last Update Submitted That Met QC Criteria: March 24, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Breast Cancer; SHR-A1811; HS-10352
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Receptor Antagonists; Estrogen Antagonists; Fulvestrant
• Other Study ID Numbers: 2024-528

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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