NCT07151586

Testing Two Different Drugs (Sacituzumab-govitecan and Trastuzumab-deruxtecan) Combinations Prescribed in an Alterning Pattern to Patients With Metastatic or Locally Advanced Triple-negative Breast Cancer

A Phase 2, Multicenter, Randomized, Open-label Trial Assessing Sacituzumab-govitecan and Trastuzumab-deruxtecan Combinations in an Alternating Regimen for Patients With Metastatic or Locally Advanced HER2-low Triple-negative Breast Cancer

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 260 (estimated)
• Sponsor: UNICANCER · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a phase II, multicentre, open-label, randomised controlled trial (patients are randomly assigned to one treatment arm or the other) evaluating two treatment strategies (sacituzumab govitecan and trastuzumab deruxtecan in an alternative schema or sacituzumab govitecan alone) in patients with locally advanced or metastatic triple-negative breast cancer. The goal is to answer the question: Does alternating sacituzumab goveitecan (SG) and trastuzumab deruxtecan (T-DXd) improve survival in patients with HER2-low metastatic triple-negative breast cancer compared to continuing treatment with SG alone?

Detailed description

Patients with locally advanced or metastatic triple-negative breast cancer (mTNBC) have poor survival outcomes Among mTNBC, about 40% of tumors have a low expression of HER2 (HER2-low; defined as IHC 2+/ISH or IHC 1+). Two antibody-drug conjugates (ADCs) have been approved for HER2-low mTNBC: sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) that target TROP2 and HER2 at the tumor cell surface, respectively. Each of these ADCs, used as monotherapy, outperformed conventional chemotherapy according to the ASCENT and DESTINY-Breast 04 trials and thereby have become the new second or third line standard of care for HER2-low mTNBC. However, as with other types of treatments, resistance is inescapable mostly due to intra-tumor heterogeneity. In the case of ADCs, resistance mechanisms involve changes in tumor antigen expression, ADC intracellular uptake and processing, and efflux of the ADC cytotoxic payload. Consequently, SG and T-DXd are used sequentially after progression even though the most effective sequence has so far been scarcely investigated and remains to be established The ASCENT trial was designed to compare the efficacy of SG with chemotherapy in patients with mTNBC and reported significantly greater progression-free and overall survival compared with the physician's choice of chemotherapy. On the other hand, the DESTINY-Breast-04 compared the efficacy of T-DXd with chemotherapy but included just 63 patients with HER2-low mTNBC. Despite a significantly longer progression-free and overall survival were observed compared with the physician's choice of chemotherapy the efficacy analysis of T-DXd in this subpopulation was not a prespecified endpoint of the trial. Even though, collectively these results have contributed to a treatment paradigm shift for mTNBC, the superiority to chemotherapy can only be formally claimed for SG in mTNBC patients and for T-DXd in HER2-low metastatic breast cancer patients We hypothesize that an upfront alternating SG and T-DXd regimen would have a greater antitumor effect compared with their prescription at progression while limiting the emergence of drug resistance. Hence, the ALTER trial aims to compare the efficacy and safety of an upfront alternating SG and T-DXd regimen with SG alone in HER2-low mTNBC patients

Conditions

• Triple Negative Breast Neoplasms
• Neoplasm Metastasis
• HER 2 Low-expressing Breast Cancer

Interventions

Type	Name	Description
DRUG	Sacituzumab Govitecan / Trastuzumab Deruxtecan	Sacituzumab govitecan is administered intravenously at a dose of 10 mg/kg on Day 1 and Day 8 of each 3-week cycle. In this study, patients receive two cycles of sacituzumab govitecan followed by two cycles of trastuzumab deruxtecan, alternating throughout the study. Trastuzumab deruxtecan is administered intravenously at a dose of 5.4 mg/kg on Day 1 of each 3-week cycle. In this study, patients receive two cycles of trastuzumab deruxtecan followed by two cycles of sacituzumab govitecan, alternating throughout the study. Both Treatment are continued until disease progression as defined by RECIST 1.1, unacceptable toxicity, withdrawal of consent, or the end of the study.

Timeline

• Start date: 2025-10-01
• Primary completion: 2029-10-01
• Completion: 2029-10-01
• First posted: 2025-09-03
• Last updated: 2025-09-03

Locations

2 sites across 1 country: France