NCT07368543

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

Sequencing Sacituzumab Govitecan vs. Trastuzumab Deruxtecan in HER2-LOw/TROP2-High Metastatic Breast Cancer: A Randomized Phase II Study

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 216 (estimated)
• Sponsor: Fudan University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

This investigator-initiated study aims to evaluate the efficacy of sequential treatment with sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) in patients with HER2 IHC 1+ /Trop-2-high metastatic breast cancer. It will also explore the correlation between changes in tumor-associated protein expression levels and ADC efficacy, and investigate mechanisms of ADC resistance. The study will establish a multicenter cohort of patients treated with SG/T-DXd: Cohort A (Triple-Negative Breast Cancer, TNBC): Includes patients with unresectable locally advanced or metastatic triple-negative breast cancer (HER2 IHC 1+) who have received ≥1 prior line of systemic therapy for metastatic disease. Prior to enrollment, all patients will undergo Trop-2 expression testing. Patients identified as Trop-2-high will be randomized 1:1 to either:SG Treatment (Trop-2 Group), orT-DXd Treatment (HER2 Group). The initially administered ADC is designated as ADC1. Upon disease progression, patients may cross over to receive the other ADC as sequential therapy (designated as ADC2). One intervening non-ADC therapy (e.g., targeted therapy, chemotherapy) is permitted prior to cross-over. Randomization will maintain a 1:1 allocation between the Trop-2 and HER2 groups. Cohort B (HR+/HER2-ultralow or HER2 IHC 1+ Breast Cancer): Includes patients with unresectable locally advanced or metastatic HR+/HER2-ultralow or HER2 IHC 1+ breast cancer who have progressed on prior endocrine therapy. Prior to enrollment, all patients will undergo Trop-2 expression testing. Patients identified as Trop-2-high will be randomized 1:1 to either:SG Treatment (Trop-2 Group), orT-DXd Treatment (HER2 Group). Upon progression, patients may cross over to receive the other ADC as sequential therapy. One intervening non-ADC therapy (e.g., targeted therapy, chemotherapy) is permitted prior to cross-over. Randomization will maintain a 1:1 allocation between the Trop-2 and HER2 groups.

Conditions

• Metastatic Breast Cancer

Interventions

Type	Name	Description
DRUG	Sacituzumab Govitecan	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.
DRUG	Trastuzumab Deruxtecan	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.

Timeline

• Start date: 2026-01-16
• Primary completion: 2027-06-01
• Completion: 2028-12-01
• First posted: 2026-01-26
• Last updated: 2026-01-28