Study on ctDNA-guided Treatment Decision-making for HER2-negative Metastatic Breast Cancer
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Fudan University
- Enrollment
- 122
- Locations
- 1
- Primary Endpoint
- Progression-Free Survival (PFS) in TNBC (Group A vs Group B)
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
ADC + Ivonescimab
Patients with <50% mean ctDNA VAF reduction receive ADC combined with ivonescimab.
Intervention: ADC (Drug)
ADC + Ivonescimab
Patients with <50% mean ctDNA VAF reduction receive ADC combined with ivonescimab.
Intervention: Ivonescimab (Drug)
ADC Monotherapy
Patients with <50% mean ctDNA VAF reduction receive continued ADC monotherapy.
Intervention: ADC (Drug)
ADC Monotherapy (ctDNA responder cohort)
Patients with ≥50% mean ctDNA VAF reduction continue ADC monotherapy.
Intervention: ADC (Drug)
Outcomes
Primary Outcomes
Progression-Free Survival (PFS) in TNBC (Group A vs Group B)
Time Frame: From randomization until progression or death (up to 36 months)
Time from randomization to disease progression or death, assessed by RECIST v1.1.
Secondary Outcomes
- ORR (RECIST v1.1)，DoR，CBR，OS，Safety (CTCAE v5.0)(From treatment initiation until end of follow-up)
Investigators
Hongxia Wang
Prof. Hongxia Wang
Fudan University