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

Phase 1

Not yet recruiting

• Conditions: Breast Cancer; Locally Advanced or Metastatic Breast Cancer
• Interventions: Drug: SHR-A1811+fulvestrant; Drug: SHR-A1811 +Fulvestrant +HS-10352; Drug: SHR-A1811+ Fulvestrant; Drug: SHR-A1811+ Fulvestrant+HS-10352

• Registration Number: NCT06788197
• Lead Sponsor: Henan Cancer Hospital

Brief Summary

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.

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 Timeline

• Study First Submitted: 2025-01-21
• Study First Submitted QC: 2025-01-21
• Status Verified: 2025-03
• Study Start: 2025-03
• Last Update Submitted: 2025-03-24
• Study First Posted: 2025-03-25
• Last Update Posted: 2025-03-26
• Primary Completion: 2028-03-31
• Study Completion: 2029-03-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 52

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort A	SHR-A1811+fulvestrant	SHR-A1811+fulvestrant
Cohort B	SHR-A1811 +Fulvestrant +HS-10352	SHR-A1811+Fulvestrant+HS-10352
SHR-A1811 + fulvestrant group	SHR-A1811+ Fulvestrant	Subjects will receive SHR-A1811 combined with fulvestrant therapy.
HS-10352 group	SHR-A1811+ Fulvestrant+HS-10352	Subjects will receive SHR-A1811 combined with Fulvestrant and HS-10352 therapy.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) according to RECIST1.1 （SHR-A1811+fulvestrant group and HS-10352 group (Phase II)）	Up to approximately 4 years	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
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

Name	Time	Method
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) （SHR-A1811 + fulvestrant group and HS-10352 group (Phase II)）	Up to approximately 4 years	Evaluate the incidence and severity of adverse events according to CTCAE 5.0
Objective Response Rate (ORR) according to RECIST1.1 （HS-10352 group(Phase Ib)）	Up to approximately 4 years	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
Progression-Free Survival (PFS)（SHR-A1811 +fulvestrant group and HS-10352 group (Phase Ib/Phase II)）	Up to 4 years	PFS is defined as the time from the first therapeutic dose to death or disease progression
Overall Survival (OS) （SHR-A1811 +fulvestrant group and HS-10352 group (Phase Ib/Phase II)）	Up to 4 years	OS is defined as the time from the first therapeutic dose to death from any cause
Clinical Benefit Rate (CBR) （CR+ PR+ SD≥24weeks）（SHR-A1811 +fulvestrant group and HS-10352 group (Phase Ib/Phase II)）	Up to 4 years	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
Duration of Response (DOR) （SHR-A1811 +fulvestrant group and HS-10352 group (Phase Ib/Phase II)）	Up to 4 years	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)