Using blood ctDNA changes to guide treatment for HER2‑negative metastatic breast cancer

Study on ctDNA-guided Treatment Decision-making for HER2-negative Metastatic Breast Cancer

This study will try using early drops in circulating tumor DNA (ctDNA) after two cycles of antibody‑drug conjugate therapy to decide whether to intensify treatment for people with HER2‑negative metastatic breast cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 122 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07394218 on ClinicalTrials.gov

What this trial studies

This is an exploratory, multi‑stage Phase 2 study that gives all enrolled patients two cycles of an antibody‑drug conjugate (ivonescimab) with blood samples collected before Cycle 1 and before Cycle 2 to measure ctDNA variant allele frequency (VAF). In Stage 2, patients without radiographic progression are assigned to different treatment strategies based on the percentage reduction in mean ctDNA VAF after those two cycles. The protocol tests whether early ctDNA VAF dynamics can serve as a biomarker to trigger treatment intensification for patients showing inadequate ctDNA decline. Clinical outcomes and safety will be followed to determine if ctDNA‑guided decisions improve disease control compared with standard approaches.

Who should consider this trial

Good fit: Adults aged 18–75 with histologically confirmed HER2‑negative metastatic breast cancer, ECOG 0–1, at least one measurable lesion, adequate organ and bone marrow function, and willingness to provide tumor tissue and serial blood samples are eligible.

Not a fit: Patients with active or untreated CNS metastases, prior treatment with an ADC targeting the same antigen/payload, active uncontrolled infection or autoimmune disease, significant cardiovascular or pulmonary comorbidity, or very low/undetectable ctDNA levels may not receive benefit from ctDNA‑guided decisions.

Why it matters

Potential benefit: If successful, this approach could help identify non‑responding patients earlier so clinicians can intensify therapy sooner and potentially improve disease control while sparing others from unnecessary treatment changes.

How similar studies have performed: Prior work has shown ctDNA dynamics can predict response in multiple cancer types and in early breast cancer, but using ctDNA to guide treatment intensification in HER2‑negative metastatic breast cancer is still experimental and not yet proven.

Eligibility criteria

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

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Hongxia WANG

Conditions Metastatic Breast Cancer; ctDNA