NCT07405476

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

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 38 (estimated)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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).

Detailed description

PRIMARY OBJECTIVE: I. To determine the activity of neoadjuvant zanidatamab in HER2+ve (RAS wild type \[RAS WT\]) locally advanced colorectal cancer. SECONDARY OBJECTIVES: I. 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: I. To determine the activity of neoadjuvant zanidatamab in HER2+ve (RAS wild type \[RAS WT\]) locally advanced colorectal cancer. SECONDARY OBJECTIVES: I. 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: I. 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.

Conditions

• Colon Carcinoma
• Colorectal Carcinoma
• Rectal Carcinoma
• Stage I Colon Cancer AJCC v8
• Stage I Colorectal Cancer AJCC v8
• Stage I Rectal Cancer AJCC v8
• 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

Interventions

Type	Name	Description
BIOLOGICAL	Zanidatamab	Given IV
PROCEDURE	Resection	Undergo surgical resection
OTHER	Patient Observation	Undergo observation
PROCEDURE	Echocardiography Test	Undergo echocardiography
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA scan
PROCEDURE	Endoscopic Procedure	Undergo sigmoidscopy
PROCEDURE	Computed Tomography	Undergo CT
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Biospecimen Collection	Undergo blood and/or archival tissue sample collection
PROCEDURE	Biopsy Procedure	Undergo biopsy
PROCEDURE	Digital Rectal Examination	Undergo digital rectal examination
OTHER	Electronic Health Record Review	Ancillary studies

Timeline

• Start date: 2026-04-07
• Primary completion: 2028-12-18
• Completion: 2029-12-18
• First posted: 2026-02-12
• Last updated: 2026-04-17

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study