ctDNA-guided Treatment Decision-making

ConditionsMetastatic Breast Cancer ( HER2 Negative)ctDNA

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18-75

SponsorFudan University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

ADC
Drug
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.
Ivonescimab
Drug
Ivonescimab is administered intravenously at 20 mg/kg every 3 weeks in combination with ADC therapy for patients assigned to the combination treatment arm.

Treatment groups

122 Participants

are divided into 3 treatment groups

Group A: ADC + IvonescimabExperimental treatment 2 interventions

Group B: ADC MonotherapyActive comparator 1 intervention

Group C: ADC Monotherapy (ctDNA responder cohort)Active comparator 1 intervention

Trial outcomes

Primary outcomes

Progression-Free Survival (PFS) in TNBC (Group A vs Group B)

Time from randomization to disease progression or death, assessed by RECIST v1.1.

Time frame

From randomization until progression or death (up to 36 months)

Secondary outcomes

ORR (RECIST v1.1)，DoR，CBR，OS，Safety (CTCAE v5.0)

Time frame

From treatment initiation until end of follow-up

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Fudan University

Lead sponsor

Source ClinicalTrials.gov

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