Metastatic Breast Cancer ( HER2 Negative), ctDNA
Conditions
Brief summary
This is an exploratory, ctDNA-guided, multi-stage clinical study designed to evaluate the clinical value of treatment decision-making based on circulating tumor DNA (ctDNA) variant allele frequency (VAF) dynamics in patients with HER2-negative metastatic breast cancer. All enrolled patients will receive antibody-drug conjugate (ADC) therapy for two cycles in Stage 1, with serial ctDNA assessments performed prior to Cycle 1 and Cycle 2. In Stage 2, patients without disease progression will be assigned to different treatment strategies based on the percentage reduction in mean ctDNA VAF. The study aims to assess whether ctDNA VAF dynamics can serve as an early biomarker to guide treatment intensification and improve clinical outcomes in metastatic breast cancer.
Interventions
DRUGADC
ADC therapy includes sacituzumab govitecan or trastuzumab deruxtecan administered intravenously according to standard dosing schedules. ADC treatment is given in all study stages and continued until disease progression or unacceptable toxicity.
DRUGIvonescimab
Ivonescimab is administered intravenously at 20 mg/kg every 3 weeks in combination with ADC therapy for patients assigned to the combination treatment arm.
Sponsors
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-75 years；ECOG performance status 0-1； Histologically or cytologically confirmed HER2-negative metastatic breast cancer； At least one measurable lesion per RECIST v1.1； Eligible for ADC therapy； Adequate organ and bone marrow function； Life expectancy ≥3 months； Willingness to provide tumor tissue and blood samples； Signed informed consent
Exclusion criteria
* Prior treatment with ADC targeting the same antigen and payload；History of grade ≥3 immune-related adverse events； Active or untreated CNS metastases； Active autoimmune disease requiring systemic therapy； Clinically significant cardiovascular disease； Active interstitial lung disease； Active infection including tuberculosis, HIV, hepatitis B or C； Pregnancy or breastfeeding；Investigator-determined conditions that may interfere with study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) in TNBC (Group A vs Group B) | From randomization until progression or death (up to 36 months) | Time from randomization to disease progression or death, assessed by RECIST v1.1. |
Secondary
| Measure | Time frame |
|---|---|
| ORR (RECIST v1.1)，DoR，CBR，OS，Safety (CTCAE v5.0) | From treatment initiation until end of follow-up |
Countries
China
Contacts
CONTACTHongxia WANG
Outcome results
None listed