Clinical trial NCT06788197: A Study of SHR-A1811 and Fulvestrant, With or Without HS-10352, in Locally Advanced or Metastatic Breast Cancer Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Locally Advanced or Metastatic Breast Cancer
Keywords: Breast Cancer
SHR-A1811
HS-10352
Lead sponsor: Henan Cancer Hospital
Sponsor class: OTHER_GOV
First posted: 2025-01-23
Enrollment: 52
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: SHR-A1811 + fulvestrant group: SHR-A1811+fulvestrant ；

HS-10352 group: SHR-A1811+Fulvestrant+HS-10352
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR) according to RECIST1.1 （SHR-A1811+fulvestrant group and HS-10352 group (Phase II)）
timeFrame: Up to approximately 4 years
measure: Recommended Phase 2 dose (RP2D) (HS-10352 group (Phase Ib))
timeFrame: From the first dose to the last dose of the first cycle defined as 28 days
Secondary outcomes:
measure: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) （SHR-A1811 + fulvestrant group and HS-10352 group (Phase II)）
timeFrame: Up to approximately 4 years
measure: Objective Response Rate (ORR) according to RECIST1.1 （HS-10352 group(Phase Ib)）
timeFrame: Up to approximately 4 years
measure: Progression-Free Survival (PFS)（SHR-A1811 +fulvestrant group and HS-10352 group (Phase Ib/Phase II)）
timeFrame: Up to 4 years
measure: Overall Survival (OS) （SHR-A1811 +fulvestrant group and HS-10352 group (Phase Ib/Phase II)）
timeFrame: Up to 4 years
measure: Clinical Benefit Rate (CBR) （CR+ PR+ SD≥24weeks）（SHR-A1811 +fulvestrant group and HS-10352 group (Phase Ib/Phase II)）
timeFrame: Up to 4 years
measure: Duration of Response (DOR) （SHR-A1811 +fulvestrant group and HS-10352 group (Phase Ib/Phase II)）
timeFrame: Up to 4 years
Other outcomes:
Locations:
Study officials:
affiliation: Henan Cancer Hospital
name: Zhenzhen Liu, MD
role: PRINCIPAL_INVESTIGATOR
References: