This randomized phase I trial studies how well anti-semaphorin 4D (anti-SEMA4D) monoclonal antibody VX15/2503 with or without ipilimumab or nivolumab work in treating patients with stage I-III pancreatic cancer that can be removed by surgery or stage IV colorectal cancer that has spread to the liver and can be removed by surgery. Monoclonal antibodies, such as anti-SEMA4D monoclonal antibody VX15/2503, ipilimumab, and nivolumab, may interfere with the ability of tumor cells to grow and spread.
PRIMARY OBJECTIVE: To evaluate the effect of the anti-SEMA4D monoclonal antibody VX15/2503 (VX15/2503) alone and VX15/2503 in combination with immune checkpoint inhibitors, ipilimumab or nivolumab, on the immune profile in the tumor microenvironment and in peripheral blood. SECONDARY OBJECTIVE: To extend the previously reported safety profile of single agent VX15/2503 to the combination of VX15/2503 and immune checkpoint inhibitors, ipilimumab or nivolumab, in patients with pancreatic and colorectal cancer. OUTLINE: Patients are randomized to 1 of 4 arms. ARM I: Patients undergo surgery. ARM II: Patients receive anti-SEMA4D monoclonal antibody VX15/2503 intravenously (IV) over 60 minutes on day 1. Patients then proceed to surgery 22-36 days after drug administration. ARM III: Patients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes and ipilimumab IV over 90 minutes on day 1. Patients then proceed to surgery 22-36 days after drug administration. ARM IV: Patients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes and nivolumab IV over 60 minutes on day 1. Patients then proceed to surgery 22-36 days after drug administration. After completion of study treatment, patients are followed up at 90 days and then every 12 weeks thereafter.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Given IV
Given IV
Given IV
Undergo therapeutic conventional surgery
Emory University Hospital Midtown
Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
Emory Saint Joseph's Hospital
Atlanta, Georgia, United States
University of Rochester Medical Center
Rochester, New York, United States
Evaluate treatment effects of the study drugs on tumor cluster of differentiation 8+ (CD8+) T cell infiltration between the treatment groups.
CD8+ T cells in tumor samples will be identified by immunohistochemistry and immunofluorescence staining, and we will quantitate the percentage and staining of the cells in the pancreatic and liver tissue with Integrated Cellular Imaging.
Time frame: Up to 4 years from date of last treatment dose
Incidence of adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events scale version 4.0
Summary statistics will be presented for all safety analyses. Toxicities will be presented as worst toxicity per patient and will be reported as percent toxicity. Adverse events will be classified using MedDRA System Organ Classes and Preferred Terms.
Time frame: Up to 4 years from the date of last treatment dose
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