Sequencing SG vs. T-DXd in HER2-Low/TROP2-High Metastatic Breast Cancer

NCT07368543 | Not Yet Recruiting Phase 2

• 1 other identifier: 2510331-4
• Study Type: interventional
• Target: 216
• Locations: 0 countries
• Sites: N/A

Brief Summary

Currently, no phase III RCT has directly compared SG and T-DXd sequencing strategies, and the predictive role of biomarkers remains unclear. Additionally, there is no standard scoring system for Trop-2 expression. The ASCENT trial utilized an H-score method (H-score = 3×%IHC3+ + 2×%IHC2+ + 1×%IHC1+), with scores \<100, 100-200, and \>200 defining low, medium, and high Trop-2 expression, respectively.This prospective study aims to: 1) Evaluate the efficacy of SG vs. T-DXd in HER2-low/Trop-2-high metastatic breast cancer, prioritizing SG for Trop-2-high patients and T-DXd for others. 2) Compare sequential treatment outcomes-T-DXd after SG failure versus SG after T-DXd failure-to inform ADC sequencing in HER2-low disease. Up to one intervening therapy is allowed before sequencing. 3) Identify biomarkers of ADC efficacy and resistance through quantitative protein analysis to optimize patient selection.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival 1 (PFS1)

  Progression-Free Survival 1 (PFS1):Time from the initiation of the first ADC (ADC1) therapy to the first occurrence of disease progression (PD) or death from any cause, whichever occurs earlier.

  Until progression, assessed up to approximately 24 months

Secondary Outcomes (5)

• Progression-Free Survival 2 (PFS2)

  Until progression, assessed up to approximately 24 months

• Objective Response Rate (ORR1, ORR2)

  Until progression, assessed up to approximately 24 months

• Disease Control Rate (DCR

  Baseline through end of study, assessed up to 24 months]

• Overall Survival (OS)

  Until death, assessed up to approximately 24 months

• Safety Endpoints

  Up to follow-up period, approximately 24 months]

Study Arms (2)

Cohort A (Triple-Negative Breast Cancer)

EXPERIMENTAL

Patients with HER2 IHC 1+ metastatic triple-negative breast cancer (TNBC);

Drug: Sacituzumab Govitecan; Drug: Trastuzumab Deruxtecan

Cohort B (HR+/HER2 IHC 1+ and Ultralow Metastatic Breast Cancer)

EXPERIMENTAL

Patients with HR-positive/HER2 IHC 1+ and HER2 ultralow metastatic breast cancer (MBC) who have failed endocrine therapy.

Drug: Sacituzumab Govitecan; Drug: Trastuzumab Deruxtecan

Interventions

Sacituzumab Govitecan DRUG

Recommended Dose: 10 mg/kg administered by intravenous infusion on Days 1 and 8 of each 21-day treatment cycle. Continue treatment until disease progression or unacceptable toxicity.

Cohort A (Triple-Negative Breast Cancer); Cohort B (HR+/HER2 IHC 1+ and Ultralow Metastatic Breast Cancer)

Trastuzumab Deruxtecan DRUG

Dosage and Administration: The recommended dose is 5.4 mg/kg administered by intravenous infusion once every 3 weeks (21-day cycles). Continue treatment until disease progression or unacceptable toxicity.

Cohort A (Triple-Negative Breast Cancer); Cohort B (HR+/HER2 IHC 1+ and Ultralow Metastatic Breast Cancer)

Eligibility Criteria

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

You may qualify if:

• Male or female, age ≥18 years.
• ECOG performance status ≤2, with an estimated life expectancy of \>3 months.
• Histologically confirmed unresectable or metastatic breast cancer that is:HER2 IHC 1+ triple-negative breast cancer, or HR-positive/HER2-ultralow or HER2 IHC 1+ breast cancer.
• Planned to receive monotherapy with Sacituzumab Govitecan and Trastuzumab Deruxtecan.
• For triple-negative breast cancer: prior systemic therapy lines ≥1.
• For HR-positive/HER2-negative metastatic breast cancer: prior endocrine therapy is required. Prior chemotherapy, immunotherapy, or targeted therapy is allowed; 0-2 lines of chemotherapy in the advanced/metastatic setting are permitted.
• Prior treatment-related adverse events have recovered to ≤Grade 1 per NCI CTCAE v5.0 (except for alopecia, non-clinically significant or asymptomatic laboratory abnormalities).
• Presence of at least one measurable or evaluable lesion.
• Willingness to provide archival or fresh tumor tissue samples for multi-omics analysis, including:
• Baseline prior to ADC1 treatment,
• After 2 cycles of ADC1 therapy,
• At progression on ADC1 therapy or baseline prior to ADC2 therapy,
• At progression on ADC2 therapy.
• FFPE tissue blocks are preferred over unstained slides. Patients must consent to tumor biopsy; if tissue is unavailable, biopsy is not feasible, or the patient declines biopsy, eligibility may be discussed and approved by the investigator.
• No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50% within 28 days before treatment.

You may not qualify if:

• Patients meeting any of the following criteria will be excluded from the study:
• Contraindication or known hypersensitivity to sacituzumab govitecan, trastuzumab deruxtecan, or any of their components (including topoisomerase I inhibitors).
• Prior treatment with sacituzumab govitecan, trastuzumab deruxtecan, or any other drug targeting the same molecular pathway.
• History of another primary malignancy, except for:
• Malignancy treated with curative intent with no evidence of active disease for ≥2 years prior to study intervention and with low risk of recurrence, or
• Adequately treated carcinoma in situ of the cervix, stage I endometrioid carcinoma of the uterus, or non-melanoma skin cancer (e.g., basal cell carcinoma or squamous cell carcinoma).
• Active infection or uncontrolled systemic disease, including but not limited to:
• Active HIV, HBV, or HCV infection,
• Active autoimmune disease,
• Symptomatic pleural effusion, ascites, or pericardial effusion requiring drainage,
• Severe or uncontrolled cardiac disease requiring treatment,
• Poorly controlled diabetes or hypertension despite medical therapy.
• Participation in another investigational drug trial within 4 weeks prior to the first study treatment (observational studies are permitted) or major surgery within 4 weeks prior to the first study treatment.
• Prior anticancer therapy within specified timeframes:
• Chemotherapy, radiotherapy, targeted therapy, or immunotherapy within 4 weeks before the first study treatment,

Sponsors & Collaborators

• Fudan University: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

sacituzumab govitecan; trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Jian Zhang, MD

CONTACT

8664175590; syner2000@163.com

Yanchun Meng, MD

CONTACT

+8664175590; ycmclinicaltrials@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Phase I Clinical Trial Department; Professor, Chief physician of oncology department

Study Record Dates

• First Submitted: January 14, 2026
• First Posted: January 26, 2026
• Study Start: January 16, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: January 28, 2026

Record last verified: 2026-01