ctDNA-guided Treatment Decision-making

NCT07394218 | Recruiting Phase 2

• 1 other identifier: DECISION
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Breast Cancer ( HER2 Negative); ctDNA

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

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

  From treatment initiation until end of follow-up

Study Arms (3)

ADC + Ivonescimab

EXPERIMENTAL

Patients with \<50% mean ctDNA VAF reduction receive ADC combined with ivonescimab.

Drug: ADC; Drug: Ivonescimab

ADC Monotherapy

ACTIVE COMPARATOR

Patients with \<50% mean ctDNA VAF reduction receive continued ADC monotherapy.

Drug: ADC

ADC Monotherapy (ctDNA responder cohort)

ACTIVE COMPARATOR

Patients with ≥50% mean ctDNA VAF reduction continue ADC monotherapy.

Drug: ADC

Interventions

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.

ADC + Ivonescimab; ADC Monotherapy; ADC Monotherapy (ctDNA responder cohort)

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.

ADC + Ivonescimab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Hongxia WANG

CONTACT

86-138196379; whx365@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Hongxia Wang

Study Record Dates

• First Submitted: December 18, 2025
• First Posted: February 6, 2026
• Study Start: December 24, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: February 6, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)