Recruiting
Optimal Application Timing of ADC Drugs for Advanced Breast Cancer
This study plans to initiate a prospective, randomized controlled trial to investigate the optimal timing of antibody drug conjugate (ADC) therapy in the management of advanced Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer.
Primary Objective:
To compare the difference in PFS2 (Time from randomization to disease progression after second therapy) between antibody-drug conjugate (ADC) followed by chemotherapy versus chemotherapy followed by ADC in the treatment of advanced HER2-negative…
ClinicalTrials.gov IDNCT07657130
PhasePHASE2
Enrollment120
SponsorLiaoning Cancer Hospital & Institute
Age18 Years
SexFEMALE
Conditions studied
Breast Cancer Females
About this study
This study plans to initiate a prospective, randomized controlled trial to investigate the optimal timing of antibody drug conjugate (ADC) therapy in the management of advanced Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer.
Primary Objective:
To compare the difference in PFS2 (Time from randomization to disease progression after second therapy) between antibody-drug conjugate (ADC) followed by chemotherapy versus chemotherapy followed by ADC in the treatment of advanced HER2-negative breast cancer.
Secondary Objectives:
To compare overall survival (OS), adverse events, patient-reported outcomes, and cost-effectiveness between the two treatment sequences. Additionally, to identify potential biomarkers predictive of benefit from frontline ADC therapy.
Interventions
- Drug: Antibody drug conjugate — The selection of ADC agents will be based on the patient's molecular subtype. For Hormone receptor (HR)+/HER2-low patients, anti-HER2 ADCs such as trastuzumab deruxtecan may be used. For HR+/HER2-zero patients, TROP-2-targeted ADCs such as sacituzumab govitecan are preferred. For HR-/HER2-low patients, either anti-HER2 ADCs or Trophoblast cell surface antigen 2 (TROP-2) ADCs may be considered. For HR-/HER2-zero patients, TROP-2 ADCs will be used. The specific ADC regimen will be determined at the discretion of the investigators.
- Drug: Chemotherapy — The chemotherapy regimen will consist of standard second-line agents such as capecitabine, eribulin, vinorelbine, or gemcitabine. The specific chemotherapy regimen will be determined at the discretion of the investigators.
Primary outcomes
- Progression-free survival 2 (PFS2) (Up to approximately 20 months)
Eligibility information
Inclusion Criteria:
1. Female patients aged 18-75 years;
2. Histologically confirmed advanced HER2-negative breast cancer, including IHC 2+/ISH-, IHC 1+/ISH-, and IHC 0/ISH- subtypes;
3. Completed first-line combination chemotherapy for advanced/metastatic disease (specific regimen not restricted), with disease progression (PD) evaluated per RECIST criteria (HR-positive patients must have received at least one line of endocrine therapy);
4. Electrocorticography (ECOG) performance status \< 2;
5. Estimated life expectancy ≥ 12 weeks;
6. Adequate bone marrow function, defined as:
* ANC ≥ 1.5 × 10⁹/L
* Platelets ≥ 90 × 10⁹/L
* Hemoglobin ≥ 90 g/L
7. Adequate hepatic and renal function, defined as:
* Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
* AST or ALT ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver metastases)
* Creatinine clearance ≥ 60 mL/min
8. Signed informed consent obtained prior to any study-related procedures or treatments, confirming the patient's willingness to participate and comply with study requirements.
Exclusion Criteria:
1. Prior treatment with an ADC after disease recurrence or metastasis;
2. Pregnant or breastfeeding women;
3. No evaluable recurrent or metastatic lesions as defined by RECIST 1.1 criteria;
4. Symptomatic brain parenchymal and/or leptomeningeal metastases with symptoms not adequately controlled by treatment;
5. History of other malignancies within the past 5 years, except for adequately treated carcinoma in situ of the cervix, cutaneous squamous cell carcinoma, or well-controlled localized basal cell carcinoma of the skin;
6. Psychiatric disorders or other conditions that may interfere with patient compliance;
7. Recent history of serious and uncontrolled systemic diseases, such as clinically significant cardiovascular disease, pulmonary disease, metabolic disorders, or arterial/venous thromboembolic events;
8. Concurrent use of other investigational drugs, or participation in another clinical trial within 30 days prior to enrollment;
9. Known or suspected allergy to any study drug or its excipients;
10. Any other condition that, in the opinion of the investigator, renders the patient unsuitable for participation in this trial.
Study locations
- Liaoning Cancer Hospital & Institute, Shenyang, Liaoning China
Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.
Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-09-27.