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

  • End date
    Dec 29, 2024
  • participants needed
  • sponsor
    M.D. Anderson Cancer Center
Updated on 4 October 2022


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) .


Primary Objective:

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

Condition Breast Cancer, HER2-positive
Treatment Letrozole, tamoxifen, Zanidatamab
Clinical Study IdentifierNCT05035836
SponsorM.D. Anderson Cancer Center
Last Modified on4 October 2022


Yes No Not Sure

Inclusion Criteria

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
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
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
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)
Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with
minimal systemic absorption\
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)
History of life-threatening hypersensitivity to monoclonal antibodies or to
recombinant proteins or excipients in the drug formulation
Known distant metastatic disease including (CNS) metastases, symptomatic CNS
metastases, and leptomeningeal disease (LMD)
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)
Symptomatic pulmonary embolism ≤28 days
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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