AzTrials
AzTrials

Colon CarcinomaPhase 2NCT07405476

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

A Phase 2 study testing Zanidatamab, Resection and Patient Observation in people with Colon Carcinoma and Colorectal Carcinoma, run by Emory University at 4 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record

Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Zanidatamab, Resection and Patient Observation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
4 sitesUnited States
Study dates
7 Apr 2026to 18 Dec 2029
Phase
Phase 2

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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%)
Show all 19Show fewer
  • 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
  • FCBP and men treated or enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 3 months after completion of study drug administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions. This includes willingness to undergo mandatory blood sample draws for evaluation of correlatives
  • Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation.

Who cannot join

  • Participants with stage IV colon and rectal cancer even if curative intent resection is planned
  • HER2 expression that does not meet documented inclusion criteria
  • 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.

Trial locations and contacts

4 sites in 1 country. Contact the study team or a site near you to ask about taking part.

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

United States4 sites, 4 recruiting

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

    Recruiting

  • Emory University Hospital

    Atlanta, Georgia, 30322

    Kathleen Coleman, kathleen.marie.coleman@emory.edu

    Olumide B. Gbolahan, MBBS, MSc

    Recruiting

  • Emory Saint Joseph's Hospital

    Atlanta, Georgia, 30342

    Recruiting

  • Emory Decatur Hospital

    Decatur, Georgia, 30033

    Recruiting

Other trials in United States

About this study

Official title: A Phase II Clinical Trial of Neoadjuvant Zanidatamab for HER2+ Localized Colorectal Cancer

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).

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the activity of neoadjuvant zanidatamab in HER2+ve (RAS wild type [RAS WT]) locally advanced colorectal cancer.

SECONDARY OBJECTIVES:

  1. To determine the efficacy of neoadjuvant zanidatamab in HER2+ve (RAS WT) locally advanced colorectal cancer.

II. To determine the feasibility and safety of neoadjuvant zanidatamab in human epidermal growth factor receptor 2 positive (HER2+) locally advanced colorectal cancer.

TERTIARY/EXPLORATORY OBJECTIVE:

PRIMARY OBJECTIVE:

  1. To determine the activity of neoadjuvant zanidatamab in HER2+ve (RAS wild type [RAS WT]) locally advanced colorectal cancer.

SECONDARY OBJECTIVES:

  1. To determine the efficacy of neoadjuvant zanidatamab in HER2+ve (RAS WT) locally advanced colorectal cancer.

II. To determine the feasibility and safety of neoadjuvant zanidatamab in human epidermal growth factor receptor 2 positive (HER2+) locally advanced colorectal cancer.

TERTIARY/EXPLORATORY OBJECTIVE:

  1. To evaluate biomarkers associated with the activity neoadjuvant zanidatamab in HER2+ (RAS WT) locally advanced colorectal cancer.

OUTLINE: HER2 positive colon cancer patients are assigned to cohort 1 and HER2 positive rectal cancer patients are assigned to cohort 2.

COHORT 1: Patients receive zanidatamab intravenously (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 multigated acquisition (MUGA) scan, sigmoidscopy, computed tomography (CT) or magnetic resonance imaging (MRI), and blood sample collection throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.

COHORT 2: 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.

After completion of study treatment, patients are followed up at 30 days and then every 12 weeks for up to 2 years.

Being tested
Zanidatamab, Resection, Patient Observation, Echocardiography Test, Multigated Acquisition Scan
Medical subject headings
Colonic Neoplasms, Colorectal Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZanidatamabBiological

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

    Given IV

  • ResectionProcedure or surgery

    Also called Resection, resection, Surgical Resection, SURGICAL RESECTION, Surgical Resection, Surgical Resection, Surgical Resection

    Undergo surgical resection

  • Patient ObservationOther

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

    Undergo observation

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography, Echocardiography, ECHOCARDIOGRAPHY, echocardiography, Echocardiography

    Undergo echocardiography

  • Multigated Acquisition ScanProcedure or surgery

    Also called 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

    Undergo MUGA scan

  • Endoscopic ProcedureProcedure or surgery

    Also called Endoscopic Examination, Endoscopic Procedure, Endoscopy, ENDOSCOPY, Endoscopy, Endoscopy, endoscopy, Endoscopy, ES

    Undergo sigmoidscopy

  • Computed TomographyProcedure or surgery

    Also called 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

    Undergo CT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called 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

    Undergo MRI

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biological Sample Collection, Biospecimen Collected, Biospecimen Collection, Specimen Collection

    Undergo blood and/or archival tissue sample collection

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY, Biopsy, Biopsy, Biopsy, biopsy, Biopsy, Biopsy, Biopsy, Biopsy, Biopsy, BIOPSY_TYPE, BIOPSY_TYPE, BIOPSY_TYPE, Bx

    Undergo biopsy

  • Digital Rectal ExaminationProcedure or surgery

    Also called Digital Rectal Examination, digital rectal examination, DRE, DRE

    Undergo digital rectal examination

  • Electronic Health Record ReviewOther

    Ancillary studies

Study groups in NCT07405476
Study groupRoleWhat they receive
Cohort 1 (zanidatamab, surgical resection)ExperimentalPatients 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.
Receives: 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)ExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: At time of surgical resection

  2. 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.

    Measured: At 6 and 12 weeks

  3. Tumor Regression Grades (Cohort 2)

    Will be assessed in those who undergo surgical resection.

    Measured: At time of surgical resection

Secondary outcomes (7)

  1. Rate of Circulating Tumor Deoxyribonucleic Acid Clearance

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

  2. Rate of Tumor Recurrence

    Will be estimated using the Kaplan-Meier method, and a 95% confidence interval for median will be estimated using the Brookmeyer-Crowley approach.

    Measured: At 2 years

  3. Recurrence Free Survival

    Will be estimated using the Kaplan-Meier method, and a 95% confidence interval for median will be estimated using the Brookmeyer-Crowley approach.

    Measured: At 2 years

  4. Incidence of Adverse Events

    Safety will be determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. Frequencies and percentages will be used to summarize safety events.

    Measured: Up to 30 days post-discontinuation

  5. Proportion of Subjects who Complete Four Treatment Cycles (Feasibility)

    Frequencies and percentages will be used to summarize events.

    Measured: Up to 3 years

  6. Adverse Even Profile (Feasibility)

    Frequencies and percentages will be used to summarize events.

    Measured: Up to 3 years

  7. Rate of Perioperative Complications (Feasibility)

    Frequencies and percentages will be used to summarize events.

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2026
  2. Study start7 Apr 2026
  3. Primary completion18 Dec 2028 (estimated)
  4. Study completion18 Dec 2029 (estimated)

Resources

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
38 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07405476
Sponsor's protocol ID
2025P012862
Other IDs
WINSHIP6609-25, NCI-2026-00566, P30CA138292
Status last verified
Apr 2026
First submitted
5 Feb 2026
Last updated
17 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in