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

NCT04553770 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 20-001275NCI-2020-06086
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 9

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.

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

Outcome Measures

Primary Outcomes (1)

• 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).

  Baseline to surgery

Secondary Outcomes (4)

• Incidence of adverse events

  Starting cycle 1 day 1 (each cycle is 21 days), through study completion, an average of 6 months.

• Molecular changes in tumor biomarkers including Ki67 expression

  Baseline to surgery

• Clinical objective response

  Baseline to surgery

• Biomarker analyses

  Baseline to surgery

Other Outcomes (1)

• Quality of life assessment: questionnaire

  Baseline, day 1 of each cycle (each cycle is 21 days) , at study completion, an average of 6 months.

Study Arms (2)

Arm A (trastuzumab deruxtecan)

ACTIVE COMPARATOR

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.

Procedure: Therapeutic Conventional Surgery; Biological: Trastuzumab Deruxtecan

Arm B (trastuzumab deruxtecan, anastrozole)

EXPERIMENTAL

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.

Drug: Anastrozole; Procedure: Therapeutic Conventional Surgery; Biological: Trastuzumab Deruxtecan

Interventions

Anastrozole DRUG

Given PO

Also known as: Anastrazole, Arimidex, ICI D1033, ICI-D1033, ZD-1033

Arm B (trastuzumab deruxtecan, anastrozole)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Arm A (trastuzumab deruxtecan); Arm B (trastuzumab deruxtecan, anastrozole)

Trastuzumab Deruxtecan BIOLOGICAL

Given IV

Also known as: DS-8201, DS-8201a, Enhertu, Fam-trastuzumab Deruxtecan-nxki, WHO 10516

Arm A (trastuzumab deruxtecan); Arm B (trastuzumab deruxtecan, anastrozole)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Creatinine clearance \>= 30 mL/min as calculated using the Cockcroft-Gault equation or serum creatinine =\< 1.5 x upper limit of normal (ULN) (within 14 days before randomization/enrollment)
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) =\< 3 x ULN (within 14 days before randomization/enrollment)
• Total bilirubin =\< 1.5 x ULN (within 14 days of randomization/enrollment). Participants with Gilbert's syndrome with a total bilirubin =\< 2.0 times ULN and direct bilirubin within normal limits are permitted
• Serum albumin \>= 2.5 g/dL (within 14 days before randomization/enrollment)
• International normalized ratio (INR)/prothrombin time (PT) and activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (within 14 days before randomization/enrollment)

You may not qualify if:

• 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
• Corrected QT interval prolongation to \> 470 ms (females) or \> 450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram
• Known hypercoaguable disorder requiring use of anticoagulant
• Significant gastrointestinal disorders limiting absorption or tolerance of oral medications (for example, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea)
• History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
• Has multiple primary malignancies within 3 years, except:

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Translational Research in Oncology-U.S: collaborator
• Daiichi Sankyo Co., Ltd.: collaborator

Study Sites (9)

St. Joseph Heritage Healthcare

Fullerton, California, 92835, United States

RECRUITING

Cancer Blood and Specialty Clinic

Los Alamitos, California, 90720, United States

RECRUITING

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

RECRUITING

Torrance Memorial Physician Network / Cancer Care

Torrance, California, 90602, United States

RECRUITING

PIH Health

Whittier, California, 90602, United States

RECRUITING

Orlando Health, Inc. d/b/a Orlando Health UF Health Center

Orlando, Florida, 32806, United States

WITHDRAWN

Ft. Wayne Medical Oncology and Hematology, Inc.

Fort Wayne, Indiana, 46804, United States

WITHDRAWN

Cancer Center of Kansas

Wichita, Kansas, 67214, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Anastrozole; trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Nicholas P McAndrew, MD

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

TRIO-US

CONTACT

310-829-5471; ISTTeam@mednet.ucla.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2020
• First Posted: September 17, 2020
• Study Start: October 9, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: November 10, 2025

Record last verified: 2025-11

Locations

US (9)