Clinical trial · Interventional
Cohort Study on Sequential ADC Therapy in HR-positive/HER2-negative Advanced Breast Cancer
Real-world Cohort Study on Sequential Therapy With ADC Drugs Following Progression of Endocrine Therapy Guided by Molecular Biomarkers in HR-positive/HER2-negative Advanced Breast Cancer
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Breast Neoplasms | Breast Neoplasm | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| First-line SG followed by T-DXd upon progression | Drug | — | UNRESOLVED |
| First-line T-DXd followed by SG upon disease progression | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Cohort 1 (HER2 IHC 2+)
- description
- 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.
- interventionNames
- Drug: First-line T-DXd followed by SG upon disease progression
- type
- EXPERIMENTAL
- label
- Cohort 2 (HER2 IHC ≤1+)
- description
- 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.
- interventionNames
- Drug: First-line SG followed by T-DXd upon progression
Primary outcomes (1)
Eligibility
Eligibility (as posted)
- Sex
- Female
- Minimum age
- 18 Years
- Maximum age
- 85 Years
Show eligibility criteria text
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.
References
Publications (0)
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