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

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.