A Phase 2 Single-Arm Open-Label Pilot Trial Evaluating Zanidatamab (ZW25) in Patients With Early Stage HER2/Neu Positive (HER2+) Breast Cancer (BC)
NCT ID: NCT05035836
Last Updated: 2025-12-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE2
20 participants
INTERVENTIONAL
2021-11-16
2028-12-29
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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) .
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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) 1
Secondary Objective(s):
* To determine pathologic response by residual cancer burden (RCB). 1-3
* To evaluate the radiographic response and volumetric change in tumor size by ultrasound and MRI
* To evaluate tolerability and safety of zanidatamab for treatment-naïve early stage HER2+ breast cancer (BC).
* To evaluate the rate of adverse events and treatment-emergent adverse events with zanidatamab alone (for patients with hormone receptor negative tumors) or with endocrine therapy tamoxifen or letrozole (in hormone receptor positive tumors)
* To evaluate the feasibility of treating patients with early stage HER2+ breast cancer with monotherapy zanidatamab
* To determine tumor-based predictive biomarkers of response
Exploratory Objective(s):
* To assess circulating free DNA levels and dynamics as biomarkers of response
* To assess effect of zanidatamab on immune environment
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Zanidatamab
zanidatamab by vein every 2 weeks (+/- 3 days) for up to 6 doses (3 study cycles
Zanidatamab
Given IV
Letrozole
Given by PO
Tamoxifen
Given by PO
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Zanidatamab
Given IV
Letrozole
Given by PO
Tamoxifen
Given by PO
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Age \> 18 years at time of study entry.
3. Patient would be willing to undergo surgery is appropriate for surgery
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 1).
5. Tumor size \> 1 cm to ≤ 3 cm assessed by ultrasound and clinically and radiographically node negative with no known metastatic disease.
6. 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.
7. 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.
8. 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
9. 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.
10. Patient with reproductive potential must have a negative pregnancy test ≤3 days prior to the first dose of zanidatamab.
Exclusion Criteria
1. Involvement in the planning and/or conduct of the study.
2. Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
3. Has received therapy for this current diagnosis of BC including investigational therapy, endocrine therapy, targeted therapy, or chemotherapy, surgery or radiation.
4. Mean QT interval corrected for heart rate (QTc) ≥ 470 ms.
5. 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.
6. Female patients who are pregnant, breast-feeding, or of reproductive potential who are not employing an effective method of birth control.
7. Patients with uncontrolled seizures.
8. Any major surgery for any reason, within 4 weeks of the enrollment. Portacath placement will be allowed.
9. 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).
10. Known active Hepatitis B and/or Hepatitis C. Hepatitis testing is not required unless the patient has a history of Hepatitis B or C.
11. Known to be HIV positive. HIV testing is not required for those patients who are not known to be positive.
12. Total lifetime anthracycline load exceeding 360 mg/m2 doxorubicin or equivalent
13. 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:
1. Adrenal replacement steroid (dose ≤10 mg daily of prednisone or equivalent)
2. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption\\
3. Short course (≤7 days) of corticosteroid prescribed prophylactically (e.g., for contrast dye allergy) or for the treatment of a non-autoimmune condition (e.g., delayed-type hypersensitivity reaction caused by contact allergen)
14. History of life-threatening hypersensitivity to monoclonal antibodies or to recombinant proteins or excipients in the drug formulation
15. Known distant metastatic disease including (CNS) metastases, symptomatic CNS metastases, and leptomeningeal disease (LMD).
16. Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease (with exception of subjects with Gilbert's Syndrome, asymptomatic gall stones, liver metastases, or stable chronic liver disease per investigator assessment)
17. Symptomatic pulmonary embolism ≤28 days
18. Administered a live vaccine ≤4 weeks prior to randomization. Patients can get COVID vaccine that are not alive before ot during the study period, with 48 hours between vaccine administration and investigation agent administration.
18 Years
FEMALE
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Zymeworks BC Inc.
INDUSTRY
M.D. Anderson Cancer Center
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Vicente Valero
Role: PRINCIPAL_INVESTIGATOR
M.D. Anderson Cancer Center
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
M D Anderson Cancer Center
Houston, Texas, United States
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Vicente Valero
Role: primary
Related Links
Access external resources that provide additional context or updates about the study.
M D Anderson Cancer Center
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2021-09420
Identifier Type: OTHER
Identifier Source: secondary_id
2021-0358
Identifier Type: -
Identifier Source: org_study_id