ctDNA-guided Treatment Decision-making

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

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 Overview

• Status: Recruiting
• Conditions: ctDNA; Metastatic Breast Cancer ( HER2 Negative)
• Intervention / Treatment: Drug: ADC; Drug: Ivonescimab

• Study Type: Interventional
• Enrollment (Estimated): 122
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hongxia WANG; Phone Number: 86-138196379; Email: whx365@126.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ADC + Ivonescimab; Patients with <50% mean ctDNA VAF reduction receive ADC combined with ivonescimab.	Drug: ADC; 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.; Drug: Ivonescimab; Ivonescimab is administered intravenously at 20 mg/kg every 3 weeks in combination with ADC therapy for patients assigned to the combination treatment arm.
Active Comparator: ADC Monotherapy; Patients with <50% mean ctDNA VAF reduction receive continued ADC monotherapy.	Drug: ADC; 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.
Active Comparator: ADC Monotherapy (ctDNA responder cohort); Patients with ≥50% mean ctDNA VAF reduction continue ADC monotherapy.	Drug: ADC; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) in TNBC (Group A vs Group B)	Time from randomization to disease progression or death, assessed by RECIST v1.1.	From randomization until progression or death (up to 36 months)

Secondary Outcome Measures

Outcome Measure	Time Frame
ORR (RECIST v1.1)，DoR，CBR，OS，Safety (CTCAE v5.0)	From treatment initiation until end of follow-up

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: December 18, 2025
• First Submitted That Met QC Criteria: February 1, 2026
• First Posted (Actual): February 6, 2026

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 1, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: DECISION

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No