A Phase 2 Single-Arm Open-Label Pilot Trial Evaluating Zanidatamab (ZW25) in Patients With Early Stage HER2/Neu Positive (HER2+) Breast Cancer (BC)

NCT05035836 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2021-0358NCI-2021-09420
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2, single-site, single-arm open-label trial of zanidatamab in patients with early stage, low risk HER2+ BC. The primary objective is to determine the efficacy of zanidatamab for patients with early stage HER2/neu positive (HER2+) breast cancer (BC) as determined by pathologic complete response (pCR) .

Conditions

Breast Cancer; HER2-positive

Outcome Measures

Primary Outcomes (1)

• To determine the efficacy of zanidatamab for patients with early stage HER2/neu positive (HER2+) breast cancer (BC) as determined by pathologic complete response (pCR

  through study completion, an average of 1 year

Study Arms (1)

Zanidatamab

EXPERIMENTAL

zanidatamab by vein every 2 weeks (+/- 3 days) for up to 6 doses (3 study cycles

Drug: Zanidatamab; Drug: Letrozole; Drug: Tamoxifen

Interventions

Zanidatamab DRUG

Given IV

Also known as: ZW25

Zanidatamab

Letrozole DRUG

Given by PO

Zanidatamab

Tamoxifen DRUG

Given by PO

Zanidatamab

Eligibility Criteria

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

You may qualify if:

• Ability to give written informed consent
• Age \> 18 years at time of study entry.
• Patient would be willing to undergo surgery is appropriate for surgery
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 1).
• Tumor size \> 1 cm to ≤ 3 cm assessed by ultrasound and clinically and radiographically node negative with no known metastatic disease.
• HER2+ BC as defined by American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) guidelines.31 Patients may have ER+ or ER- negative disease, as defined by ASCO-CAP guidelines.
• Left ventricular ejection fraction (LVEF) must be within institutional limits of normal as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan, documented within 4 weeks prior to first dose of study drug.
• Adequate normal organ and marrow function as defined below:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (≥ 1500 per mm3)
• Platelet count ≥ 100 x 109/L (≥100,000 per mm3)
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). The maximum allowable bilirubin is ≤ 2.5 x ULN for patients with Gilbert's disease.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN
• Calculated glomerular filtration rate \>50 mL/min
• Patients must either be of non-reproductive potential or willing to undergo appropriate contraception. Male subjects must agree not to donate sperm and female subjects must agree not to donate oocytes starting at screening and throughout the study period, and for at least 12 months after treatment discontinuation.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Involvement in the planning and/or conduct of the study.
• Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Has received therapy for this current diagnosis of BC including investigational therapy, endocrine therapy, targeted therapy, or chemotherapy, surgery or radiation.
• Mean QT interval corrected for heart rate (QTc) ≥ 470 ms.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, active peptic ulcer disease or gastritis, active bleeding diatheses, , or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent.
• Female patients who are pregnant, breast-feeding, or of reproductive potential who are not employing an effective method of birth control.
• Patients with uncontrolled seizures.
• Any major surgery for any reason, within 4 weeks of the enrollment. Portacath placement will be allowed.
• Clinically significant cardiac disease such as ventricular arrhythmia requiring therapy, , myocardial infarction, unstable angina (within 6 months prior to first dose of study drug), any history of cardiac failure, and uncontrolled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications).
• Known active Hepatitis B and/or Hepatitis C. Hepatitis testing is not required unless the patient has a history of Hepatitis B or C.
• Known to be HIV positive. HIV testing is not required for those patients who are not known to be positive.
• Total lifetime anthracycline load exceeding 360 mg/m2 doxorubicin or equivalent
• Any condition that requires systemic treatment with either corticosteroids (\>10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤14 days prior to randomization. Note: Subjects who are currently or have previously been on any of the following steroid regimens are not excluded:
• Adrenal replacement steroid (dose ≤10 mg daily of prednisone or equivalent)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Zymeworks BC Inc.: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Breast Neoplasms

Interventions

zanidatamab; Letrozole; Tamoxifen

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; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Vicente Valero

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vicente Valero

CONTACT

713-563-0751; vvalero@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: August 25, 2021
• First Posted: September 5, 2021
• Study Start: November 16, 2021
• Primary Completion (Estimated): December 29, 2028
• Study Completion (Estimated): December 29, 2028
• Last Updated: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)