Breast CancerPhase 2NCT05035836
A Phase 2 Single-Arm Open-Label Pilot Trial Evaluating Zanidatamab (ZW25) in Patients With Early Stage HER2/Neu Positive (HER2+) Breast Cancer (BC)
A Phase 2 study testing Zanidatamab, Letrozole and Tamoxifen in people with Breast Cancer and HER2-positive, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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) . Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer, HER2-positive
- What is being tested?
- Zanidatamab, Letrozole and Tamoxifen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Nov 2021to 29 Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Patient with reproductive potential must have a negative pregnancy test ≤3 days prior to the first dose of zanidatamab.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
M D Anderson Cancer Center
Houston, Texas, 77030
Vicente Valero, 713-563-0751, vvalero@mdanderson.org
Vicente Valero
About this study
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) .
Read the detailed description
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
- Conditions
- Breast Cancer, HER2-positive
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Zanidatamab | Experimental | zanidatamab by vein every 2 weeks (+/- 3 days) for up to 6 doses (3 study cycles Receives: Drug: Zanidatamab; Drug: Letrozole; Drug: Tamoxifen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2021
- Study start16 Nov 2021
- Primary completion29 Dec 2028 (estimated)
- Study completion29 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Zymeworks BC Inc.
- Responsible party
- Sponsor
- Investigators
- Vicente Valero, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05035836
- Sponsor's protocol ID
- 2021-0358
- Other IDs
- NCI-2021-09420
- Status last verified
- Aug 2026
- First submitted
- 25 Aug 2021
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Valero V, Pohlmann PR, Mouabbi J, Huang X, Qiao W, Alonzo H, Murthy RK, Rauch GM, Adesoye T, Checka C, Symmans FW, Grachev D, Alajajyan F, Nwosu-Iheme A, Hassan A, Patel M, Giordano SH, Hunt K, Tripathy D, Meric-Bernstam F. Zanidatamab in patients with early stage HER2-positive breast cancer: the NeoZanHER phase 2 single-arm open-label trial. Nat Commun. 2026 Aug 22;17(1):10116. doi: 10.1038/s41467-026-76662-6.
PubMed 42773107
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Single-Arm Open-Label Pilot Trial Evaluating Zanidatamab (ZW25) in Patients With Early Stage HER2/Neu Positive (HER2+) Breast Cancer (BC)
- ClinicalTrials.gov ID
- NCT05035836
- Acronym / sponsor ID
- 2021-0358
- Conditions
- Breast Cancer, HER2-positive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Zymeworks BC Inc.
- Study start
- 16 Nov 2021 (actual)
- Primary completion
- 29 Dec 2028 (estimated)
- Study completion
- 29 Dec 2028 (estimated)
- First posted
- 5 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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) .
Detailed description
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Zanidatamab | Experimental | Drug: Zanidatamab, Drug: Letrozole, Drug: Tamoxifenzanidatamab by vein every 2 weeks (+/- 3 days) for up to 6 doses (3 study cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZanidatamabAlso: ZW25Given IV | Drug | Zanidatamab |
| LetrozoleGiven by PO | Drug | Zanidatamab |
| TamoxifenGiven by PO | Drug | Zanidatamab |
Primary outcome
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
Time frame: through study completion, an average of 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2026.
- Derived from this study: PubMed 42773107Valero V, Pohlmann PR, Mouabbi J, Huang X, Qiao W, Alonzo H, Murthy RK, Rauch GM, Adesoye T, Checka C, Symmans FW, Grachev D, Alajajyan F, Nwosu-Iheme A, Hassan A, Patel M, Giordano SH, Hunt K, Tripathy D, Meric-Bernstam F. Zanidatamab in patients with early stage HER2-positive breast cancer: the NeoZanHER phase 2 single-arm open-label trial. Nat Commun. 2026 Aug 22;17(1):10116. doi: 10.1038/s41467-026-76662-6.
- M D Anderson Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Vicente Valero principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zanidatamab, Letrozole and Tamoxifen in people with Breast Cancer and HER2-positive, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vicente Valero (713-563-0751, vvalero@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05035836, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2026.