Cohort Study on Sequential ADC Therapy in HR-positive/HER2-negative Advanced Breast Cancer

NCT ID: NCT07162259

Last Updated: 2025-09-09

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-01
• Study Completion Date: 2027-12-31

Brief Summary

The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and endocrine therapy is the standard first-line treatment for advanced HR+ (hormone receptor-positive)/HER2- (human epidermal growth factor receptor 2-negative) breast cancer. However, the optimal treatment strategy after CDK4/6i progression remains unclear. In recent years, antibody-drug conjugates (ADCs) such as sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) have demonstrated significant activity in HR+/HER2- breast cancer, providing new options post-CDK4/6i progression. Yet, the optimal sequencing of different ADCs (e.g., SG followed by T-DXd vs. T-DXd followed by SG) after CDK4/6i failure remains uncertain. Determining how to further optimize treatment selection to prolong survival and improve quality of life has become a key research focus in clinical practice. This study aims to explore the efficacy, safety, and potential resistance mechanisms of biomarker-guided sequential ADC therapy (e.g., SG→T-DXd vs. T-DXd→SG) following CDK4/6i progression. The findings may guide clinical decision-making and provide evidence for precision medicine.

Conditions

Breast Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1 (HER2 IHC 2+)

Patients will be assigned to Cohort 1 (HER2 Immunohistochemistry，IHC，2+) based on different HER2 immunohistochemical expression levels, where they will first receive T-DXd treatment, followed by SG treatment upon disease progression.

Group Type: EXPERIMENTAL

First-line T-DXd followed by SG upon disease progression

Intervention Type: DRUG

Patients will be assigned to Cohort 1 (HER2 IHC 2+) based on different HER2 immunohistochemical expression levels, where they will first receive T-DXd treatment, followed by SG treatment upon disease progression.

Cohort 2 (HER2 IHC ≤1+)

Patients will be assigned to Cohort 2 (HER2 IHC ≤1+) based on different HER2 immunohistochemical expression levels, where they will first receive SG treatment, followed by T-DXd treatment upon disease progression.

Group Type: EXPERIMENTAL

First-line SG followed by T-DXd upon progression

Intervention Type: DRUG

Patients will be assigned to Cohort 2 (HER2 IHC ≤1+) based on different HER2 immunohistochemical expression levels, where they will first receive SG treatment, followed by T-DXd treatment upon disease progression.

Interventions

First-line T-DXd followed by SG upon disease progression

Patients will be assigned to Cohort 1 (HER2 IHC 2+) based on different HER2 immunohistochemical expression levels, where they will first receive T-DXd treatment, followed by SG treatment upon disease progression.

Intervention Type: DRUG

First-line SG followed by T-DXd upon progression

Patients will be assigned to Cohort 2 (HER2 IHC ≤1+) based on different HER2 immunohistochemical expression levels, where they will first receive SG treatment, followed by T-DXd treatment upon disease progression.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Adult patients ≥18 years old;

2. Histologically or cytologically confirmed HR+/HER2- (HER2 IHC 0/IHC 1+ or IHC 2+ with FISH-negative) locally advanced unresectable or metastatic breast cancer, as defined by ASCO/CAP guidelines;

3. Prior treatment with CDK4/6i combined with endocrine therapy, with radiologically confirmed disease progression;

4. Presence of evaluable lesions;

5. Received ≤2 lines of chemotherapy for advanced disease;

6. Adequate organ function and performance status (ECOG score ≤2);

7. Signed informed consent.

Exclusion Criteria

1. Previous treatment with topoisomerase 1 (TOP-1) inhibitor-based therapy;

2. Severe cardiac, hepatic, or renal dysfunction or other serious comorbidities;

3. History of moderate to severe interstitial lung disease (ILD) with concurrent pulmonary insufficiency;

4. Symptomatic brain metastases;

5. History of allergy to key components of the investigational ADC drugs (e.g., payload, antibody, or linker);

6. Patients with active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or a history of intestinal obstruction or gastrointestinal (GI) perforation;

7. Uncontrolled cardiovascular diseases (e.g., NYHA Class III/IV heart failure, myocardial infarction within 6 months);

8. Active infections (e.g., HIV, active HBV/HCV infection);

9. Pregnant or lactating women.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Yan Xue

OTHER

Sponsor Role: lead

Responsible Party

Yan Xue

Director of the First Department of Oncology, Xi'an International Medical Center Hospital

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Yan Xue

Role: PRINCIPAL_INVESTIGATOR

Xi'an International Medical Center Hospital

Locations

Xi'an International Medical Center Hospital

Xi'an, , China

Countries

China

Central Contacts

Junmei Zhang

Role: CONTACT

zjm19870908@163.com

008618092309080

Facility Contacts

Yan Xue

Role: primary

1410605462@qq.com

0086-13992830596

Other Identifiers

IIT2025006

Identifier Type: -

Identifier Source: org_study_id