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
Overview
- Phase
- Phase 2
- Intervention
- Therapeutic Conventional Surgery
- Conditions
- Early-stage Breast Cancer
- Sponsor
- Jonsson Comprehensive Cancer Center
- Enrollment
- 88
- Locations
- 9
- Primary Endpoint
- Pathologic complete response (pCR) rate
- Status
- Recruiting
- Last Updated
- 5 months ago
Overview
Brief 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
- •Tumor is HR positive (HR+) per ASCO CAP guidelines with known estrogen and progesterone receptor status, locally defined
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Normal cardiac function (left ventricular ejection fraction \[LVEF\] \>= 50%) based on echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization/enrollment
- •Platelet count \>= 100 000/mm\^3 (Platelet transfusion is not allowed within 1 week prior to screening assessment) (within 14 days before randomization/enrollment)
- •Hemoglobin \>= 9.0 g/dL (red blood cell transfusion is not allowed within 1 week prior to screening assessment) (within 14 days before randomization/enrollment)
- •Absolute neutrophil count (ANC) \>=1500/mm\^3 (Granulocyte colony-stimulating factor (G-CSF) administration is not allowed within 1 week prior to screening assessment) (within 14 days before randomization/enrollment)
Exclusion Criteria
- •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
- •Prior tamoxifen for history of ductal breast carcinoma in situ (DCIS) allowed, but no prior aromatase inhibitor, no prior chemotherapy and no prior HER2-targeted therapy
- •Prior ipsilateral chest wall radiation
- •Major surgery \< 4 weeks prior to enrollment
- •Medical history of myocardial infarction within 6 months before randomization/enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), troponin levels consistent with myocardial infarction as defined according to the manufacturer 28 days prior to randomization
- •Unable to swallow oral medications
- •Is pregnant or lactating, or planning to become pregnant
Arms & Interventions
Arm A (trastuzumab deruxtecan)
Patients receive trastuzumab deruxtecan 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.
Intervention: Therapeutic Conventional Surgery
Arm A (trastuzumab deruxtecan)
Patients receive trastuzumab deruxtecan 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.
Intervention: Trastuzumab Deruxtecan
Arm B (trastuzumab deruxtecan, anastrozole)
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 PO 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.
Intervention: Anastrozole
Arm B (trastuzumab deruxtecan, anastrozole)
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 PO 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.
Intervention: Therapeutic Conventional Surgery
Arm B (trastuzumab deruxtecan, anastrozole)
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 PO 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.
Intervention: Trastuzumab Deruxtecan
Outcomes
Primary Outcomes
Pathologic complete response (pCR) rate
Time Frame: Baseline to surgery
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).
Secondary Outcomes
- Clinical objective response(Baseline to surgery)
- Molecular changes in tumor biomarkers including Ki67 expression(Baseline to surgery)
- Biomarker analyses(Baseline to surgery)
- Incidence of adverse events(Starting cycle 1 day 1 (each cycle is 21 days), through study completion, an average of 6 months.)