| Eligibility |
Inclusion Criteria:
1. Ability to give written informed consent
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
An individual who meets any of the following criteria will be excluded from participation
in this study:
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.
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