NCT04553770

Trastuzumab Deruxtecan Alone or in Combination With Anastrozole for the Treatment of Early Stage HER2 Low, Hormone Receptor Positive Breast Cancer

A Phase II, Multicenter, Open-Label Trial to Evaluate the Safety and Efficacy of Trastuzumab Deruxtecan (DS-8201a) With or Without Anastrozole for HER2 Low Hormone Receptor Positive (HR+) Breast Cancer in the Neoadjuvant Setting

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 88 (estimated)
• Sponsor: Jonsson Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial investigates how well trastuzumab deruxtecan works alone or in combination with anastrozole in treating patients with HER2 low, hormone receptor positive breast cancer. Trastuzumab deruxtecan is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug called deruxtecan. Trastuzumab attaches to HER2 expressed at low levels on cancer cells in a targeted way and delivers deruxtecan to kill them. Anastrozole works by decreasing estrogen production and suppressing the growth of tumors that need estrogen to grow. This study is evaluating how effective trastuzumab deruxtecan is at treating hormone receptor positive cancer cells that have low levels of HER2 expressed on them when given alone or in combination with anastrozole.

Detailed description

PRIMARY OBJECTIVE: I. To identify treatment arm with strongest signal of efficacy, based on pathologic complete response (pCR) rate, between two neoadjuvant systemic therapy regimens in participants with early stage, HER2 low, hormone receptor positive (HR+) breast cancer. SECONDARY OBJECTIVES: I. To assess the safety profile of the two novel neoadjuvant experimental arms. II. To assess the molecular changes in tumor biomarkers including Ki67 after 1 cycle of targeted therapy. III. Pathological Assessment According to Residual Cancer Burden (RCB) Index at surgery. IV. To investigate potential serum and tumor predictive biomarkers to predict response to experimental therapy. EXPLORATORY OBJECTIVES: I. To investigate potential serum and tumor predictive biomarkers to predict response to experimental therapy. II. To assess quality of life by evaluating toxicity burden using a quality of life (QOL)/patient reported outcomes (PRO) questionnaire- the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30) instrument. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive trastuzumab deruxtecan intravenously (IV) over 90 minutes on cycle 1 day 1 and 30 minutes on day 1 of each subsequent cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. ARM B: Patients receive trastuzumab deruxtecan IV over 90 minutes on cycle 1 day 1 and 30 minutes on day 1 of each subsequent cycle and anastrozole orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. After completion of study treatment, patients are followed up at 21-28 days.

Conditions

• Early-stage Breast Cancer
• Hormone Receptor Positive Breast Carcinoma
• Invasive Breast Cancer
• Stage II Breast Cancer
• Stage IIA Breast Cancer
• Stage IIB Breast Cancer
• Stage III Breast Cancer

Interventions

Type	Name	Description
DRUG	Anastrozole	Given PO
PROCEDURE	Therapeutic Conventional Surgery	Undergo surgery
BIOLOGICAL	Trastuzumab Deruxtecan	Given IV

Timeline

• Start date: 2020-10-09
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2020-09-17
• Last updated: 2025-11-10

Locations

9 sites across 1 country: United States

Regulatory

• FDA-regulated drug study