Zanidatamab Before Surgery for the Treatment of HER2 Positive Colon and Rectal Cancer in Patients Planned for Curative Intent Treatment

NCT07405476 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: 2025P012862WINSHIP6609-25NCI-2026-00566P30CA138292
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 4

Brief Summary

This phase II trial studies how well giving zanidatamab before surgery (neoadjuvant) works in treating patients with colon and rectal cancer that is human epidermal growth factor receptor 2 positive (HER2+ve) who are planned for curative intent treatment. Zanidatamab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens).

Conditions

Stage II Colon Cancer AJCC v8; Stage II Colorectal Cancer AJCC v8; Stage II Rectal Cancer AJCC v8; Stage III Colon Cancer AJCC v8; Stage III Colorectal Cancer AJCC v8; Stage III Rectal Cancer AJCC v8; Colon Carcinoma; Colorectal Carcinoma; Rectal Carcinoma; Stage I Colon Cancer AJCC v8; Stage I Colorectal Cancer AJCC v8; Stage I Rectal Cancer AJCC v8

Outcome Measures

Primary Outcomes (3)

• Rate of Complete and Major Pathologic Regression (Cohort 1)

  For colon cancer, will evaluate the rate of complete and major pathologic regression in the surgical specimen based on the modified Dworak grading system. Will be reported as a proportion, and 95% exact binomial confidence interval. Will be estimated using the Clopper-Pearson method.

  At time of surgical resection

• Radiologic Response (Cohort 2)

  Assessment will be by computed tomography chest, abdomen and magnetic resonance imaging of the rectum. Radiologic tumor response will be based on Response Evaluation Criteria in Solid Tumors 1.1. Will be reported as a proportion, and 95% exact binomial confidence interval. Will be estimated using the Clopper-Pearson method.

  At 6 and 12 weeks

• Tumor Regression Grades (Cohort 2)

  Will be assessed in those who undergo surgical resection.

  At time of surgical resection

Secondary Outcomes (7)

• Rate of Circulating Tumor Deoxyribonucleic Acid Clearance

  Before cycle 1 day 1 of treatment and preoperatively for colon cancer patients or at 6 and 12 weeks for rectal cancer patients

• Rate of Tumor Recurrence

  At 2 years

• Recurrence Free Survival

  At 2 years

• Incidence of Adverse Events

  Up to 30 days post-discontinuation

• Proportion of Subjects who Complete Four Treatment Cycles (Feasibility)

  Up to 3 years

Study Arms (2)

Cohort 1 (zanidatamab, surgical resection)

EXPERIMENTAL

Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection on study followed by adjuvant chemotherapy as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT or MRI, and blood sample collection throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.

Biological: Zanidatamab; Procedure: Resection; Other: Patient Observation; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Procedure: Endoscopic Procedure; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection; Procedure: Biopsy Procedure; Procedure: Digital Rectal Examination; Other: Electronic Health Record Review

Cohort 2 (zanidatamab)

EXPERIMENTAL

Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients then optionally undergo surgical resection or observation as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT, MRI, blood sample collection, and digital rectal exam throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.

Biological: Zanidatamab; Procedure: Resection; Other: Patient Observation; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Procedure: Endoscopic Procedure; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection; Procedure: Biopsy Procedure; Procedure: Digital Rectal Examination; Other: Electronic Health Record Review

Interventions

Zanidatamab BIOLOGICAL

Given IV

Also known as: 2169946-15-8, Anti-HER2/HER2 Bispecific Antibody ZW25,, HER2 x HER2 Bispecific Antibody ZW25, ZANIDATAMAB, Zanidatamab-hrii, Ziihera, ZW-25, ZW25

Cohort 1 (zanidatamab, surgical resection); Cohort 2 (zanidatamab)

Resection PROCEDURE

Undergo surgical resection

Also known as: Resection, resection, Surgical Resection, SURGICAL RESECTION, Surgical Resection, Surgical Resection, Surgical Resection

Cohort 1 (zanidatamab, surgical resection); Cohort 2 (zanidatamab)

Patient Observation OTHER

Undergo observation

Also known as: active surveillance, Active Surveillance, deferred therapy, expectant management, observation, Observation, watchful waiting, Watchful Waiting

Cohort 1 (zanidatamab, surgical resection); Cohort 2 (zanidatamab)

Echocardiography Test PROCEDURE

Undergo echocardiography

Also known as: EC, Echocardiography, Echocardiography, ECHOCARDIOGRAPHY, echocardiography, Echocardiography

Cohort 1 (zanidatamab, surgical resection); Cohort 2 (zanidatamab)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA scan

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide, Ventriculogram Scan, Radionuclide Ventriculography, Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Cohort 1 (zanidatamab, surgical resection); Cohort 2 (zanidatamab)

Endoscopic Procedure PROCEDURE

Undergo sigmoidscopy

Also known as: Endoscopic Examination, Endoscopic Procedure, Endoscopy, ENDOSCOPY, Endoscopy, Endoscopy, endoscopy, Endoscopy, ES

Cohort 1 (zanidatamab, surgical resection); Cohort 2 (zanidatamab)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computed Tomography, Computed Tomography,, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography,, Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Cohort 1 (zanidatamab, surgical resection); Cohort 2 (zanidatamab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging, Magnetic Resonance Imaging, Magnetic Resonance Imaging, magnetic resonance imaging,, Magnetic Resonance Imaging, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging,, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR, MR Imaging, MRI, MRI, MRI, MRI, MRI, MRI,, MRI Scan, MRI Scan, MRI Scan, MRI Scan, MRIs, NMR Imaging, NMRI, NMRI, nuclear magnetic resonance imaging, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Cohort 1 (zanidatamab, surgical resection); Cohort 2 (zanidatamab)

Biospecimen Collection PROCEDURE

Undergo blood and/or archival tissue sample collection

Also known as: Biological Sample Collection, Biological Sample Collection, Biospecimen Collected, Biospecimen Collection, Specimen Collection

Cohort 1 (zanidatamab, surgical resection); Cohort 2 (zanidatamab)

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY, Biopsy, Biopsy, Biopsy, biopsy, Biopsy, Biopsy, Biopsy, Biopsy, Biopsy, BIOPSY_TYPE, BIOPSY_TYPE, BIOPSY_TYPE, Bx

Cohort 1 (zanidatamab, surgical resection); Cohort 2 (zanidatamab)

Digital Rectal Examination PROCEDURE

Undergo digital rectal examination

Also known as: Digital Rectal Examination, digital rectal examination, DRE, DRE

Cohort 1 (zanidatamab, surgical resection); Cohort 2 (zanidatamab)

Electronic Health Record Review OTHER

Ancillary studies

Cohort 1 (zanidatamab, surgical resection); Cohort 2 (zanidatamab)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed colon and/or rectal cancer planned for curative intent treatment at gastrointestinal clinics of Emory University's Winship Cancer Institute and collaborating centers
• Tumors must be HER2+ve (human epidermal growth factor receptor 2 \[HER2\] overexpression 3+ immunohistochemistry \[IHC\] or 2+ by IHC and positive fluorescence in situ hybridization \[FISH\] or HER2 amplification by next generation sequencing)
• Tumors must have RAS wildtype genotype
• Radiologically measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 50%)
• Platelet count \> 100,000 cells/ ul (within 28 days of cycle 1 day 1, at the discretion of the investigator)
• Hemoglobin \> 9g/dl (within 28 days of cycle 1 day 1, at the discretion of the investigator)
• Absolute neutrophil count \> 1000 cells/dl (within 28 days of cycle 1 day 1, at the discretion of the investigator)
• Aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN) (within 28 days of cycle 1 day 1, at the discretion of the investigator)
• Alanine aminotransferase (ALT) ≤ 3 × ULN (within 28 days of cycle 1 day 1, at the discretion of the investigator)
• Total bilirubin ≤ 1.5 × ULN, or ≤ 3 × ULN for participants with Gilbert's disease (within 28 days of cycle 1 day 1, at the discretion of the investigator)
• Glomerular filtration rate (GFR) \> 60ml/min (based on creatine, and Cystatin C estimation where applicable) (within 28 days of cycle 1 day 1, at the discretion of the investigator)
• Adequate cardiac function with left ventricular ejection fraction of at least 50% (within 28 days of cycle 1 day 1, at the discretion of the investigator)
• Females of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy

You may not qualify if:

• Participants with stage IV colon and rectal cancer even if curative intent resection is planned
• RAS mutation
• MSI-H or mismatch repair deficient rectal cancer
• Clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension or any history of symptomatic congestive heart failure (CHF). Participants with known myocardial infarction or unstable angina within 6 months prior to expected date of cycle 1 day 1 (C1D1) are also excluded. Previous anticancer therapy-related CHF must have been ≤ grade 1 at the time of occurrence and must have completely resolved
• Participants receiving any other investigational agents or an investigational device within 28 days of administering the first dose of study drug
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in study
• Uncontrolled current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

RECRUITING

Emory University Hospital

Atlanta, Georgia, 30322, United States

RECRUITING

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

RECRUITING

Emory Decatur Hospital

Decatur, Georgia, 30033, United States

RECRUITING

MeSH Terms

Conditions

Colonic Neoplasms; Colorectal Neoplasms; Rectal Neoplasms

Interventions

zanidatamab; Watchful Waiting; Observation; Radioisotopes; Cerebral Ventriculography; Endoscopy; Magnetic Resonance Spectroscopy; X-Rays; Specimen Handling; Biopsy

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Methods; Investigative Techniques; Isotopes; Inorganic Chemicals; Neuroradiography; Neuroimaging; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Radiography; Diagnostic Techniques, Neurological; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Clinical Laboratory Techniques; Cytodiagnosis; Cytological Techniques

Study Officials

• Olumide B. Gbolahan, MBBS, MSc

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Olumide B. Gbolahan, MBBS, MSc

CONTACT

404-778-1900; ogbolah@emory.edu

Patrick Sullivan, MD, FACS

CONTACT

404-778-2656; patrick.s.sullivan@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 5, 2026
• First Posted: February 12, 2026
• Study Start: April 7, 2026
• Primary Completion (Estimated): December 18, 2028
• Study Completion (Estimated): December 18, 2029
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

US (4)