Optimal Application Timing of ADC Drugs for Advanced Breast Cancer
A Prospective, Randomized Controlled Phase II Trial Investigating the Optimal Timing of Antibody Drug Conjugates in Advanced HER2-Negative Breast Cancer Patients
Liaoning Cancer Hospital & Institute
120 participants
Jul 1, 2025
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria14
- Female patients aged 18-75 years;
- Histologically confirmed advanced HER2-negative breast cancer, including IHC 2+/ISH-, IHC 1+/ISH-, and IHC 0/ISH- subtypes;
- 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);
- Electrocorticography (ECOG) performance status < 2;
- Estimated life expectancy ≥ 12 weeks;
- Adequate bone marrow function, defined as:
- ANC ≥ 1.5 × 10⁹/L
- Platelets ≥ 90 × 10⁹/L
- Hemoglobin ≥ 90 g/L
- 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
- 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 Criteria10
- Prior treatment with an ADC after disease recurrence or metastasis;
- Pregnant or breastfeeding women;
- No evaluable recurrent or metastatic lesions as defined by RECIST 1.1 criteria;
- Symptomatic brain parenchymal and/or leptomeningeal metastases with symptoms not adequately controlled by treatment;
- 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;
- Psychiatric disorders or other conditions that may interfere with patient compliance;
- Recent history of serious and uncontrolled systemic diseases, such as clinically significant cardiovascular disease, pulmonary disease, metabolic disorders, or arterial/venous thromboembolic events;
- Concurrent use of other investigational drugs, or participation in another clinical trial within 30 days prior to enrollment;
- Known or suspected allergy to any study drug or its excipients;
- Any other condition that, in the opinion of the investigator, renders the patient unsuitable for participation in this trial.
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Interventions
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.
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.
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT07657130