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.
Previously untreated operable invasive carcinoma of the breast greater than 2.0 cm (cT2) in size based on physical exam or imaging. Patients with clinical node negative disease or clinical node (cN1/cN2) positive are allowed provided they are deemed to have operable disease at study entry
Participants with clinically involved lymph nodes should not have radiological evidence of distant disease per standard of care staging prior to patient informed consent form (PICF) signature
In the United States
Tumor is HER2-low by immunohistochemistry (IHC), defined as 1+ or 2+, confirmed by central testing (central testing results not required for enrollment, unless no local results available). If HER2 is 2+ by IHC, fluorescence in situ hybridization (FISH) must be performed (per standard of care) and the FISH result must be HER2 non-amplified per 2018 American Society of Clinical Oncology College of American Pathologists (ASCO CAP) guidelines
Recurrent or metastatic breast cancer
Bilateral breast cancer (multifocal or multicentric breast cancer is allowed provided that all biopsied lesions are HER2 1+ or 2+, not FISH amplified and are HR positive per ASCO guidelines)
Inflammatory breast cancer
Prior systemic therapy for invasive cancer
Parallel
Anastrozole
DrugGiven PO
Therapeutic Conventional Surgery
Procedure/SurgeryUndergo surgery
Trastuzumab Deruxtecan
Biological/VaccineGiven IV
Pathologic complete response (pCR) rate
pCR is defined as the absence of invasive cancer in the breast and sampled regional lymph nodes. pCR will be calculated along with the corresponding exact 95% Clopper-Pearson confidence interval (CI).
Incidence of adverse events
Overall exposure to study drug, the numbers of participants completing each cycle, and the dose intensity will be summarized using descriptive statistics. The number of participants with any dose adjustment will be presented for entire treatment period as well as for each cycle. The number of participants with dose reductions, dose delays, or dose omissions will also be summarized, as will the reasons for dose adjustments. Adverse events and serious adverse events will be reported using a Common Terminology Criteria for Adverse Events version 5.0 terminology and severity.
Molecular changes in tumor biomarkers including Ki67 expression
Percent change in Ki67 expression from baseline to the core biopsy obtained between cycle 1 day 17 and cycle 1 day 21, and surgery.
Clinical objective response
Clinical objective response rate will be estimated and 95% exact Clopper-Pearson CIs will be provided.
Biomarker analyses
Gene expression and biomarker assay results are exploratory and will be summarized (e.g. mean change in from baseline to during treatment and to prior to surgery) and correlated with clinical outcomes as appropriate.
Quality of life assessment: questionnaire
Will assess quality of life by evaluating toxicity burden using a quality of life/patient reported outcome questionnaire- the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 instrument.
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Jonsson Comprehensive Cancer Center
Lead sponsor
Translational Research in Oncology-U.S
Collaborator
Daiichi Sankyo Co., Ltd.
Collaborator
