VX15/2503 and Immunotherapy in Resectable Pancreatic and Colorectal Cancer

NCT03373188 | Completed Phase 1 DMC FDA Drug

• 4 other identifiers: IRB00098707NCI-2017-01618Winship4142-17P30CA138292
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Colon Carcinoma Metastatic in the Liver; Colorectal Adenocarcinoma; Pancreatic Adenocarcinoma; Resectable Pancreatic Carcinoma; Stage I Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Colorectal Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 4 years from date of last treatment dose

Secondary Outcomes (1)

• Incidence of adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events scale version 4.0

  Up to 4 years from the date of last treatment dose

Study Arms (4)

Arm I (surgery)

ACTIVE COMPARATOR

Patients undergo surgery.

Procedure: Surgery

Arm II (VX15/2503, surgery)

EXPERIMENTAL

Patients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes on day 1. Beginning 22-36 days after administration, patients undergo surgery.

Biological: Anti-SEMA4D Monoclonal Antibody VX15/2503; Procedure: Surgery

Arm III (VX15/2503, ipilimumab, surgery)

EXPERIMENTAL

Patients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes and ipilimumab IV over 90 minutes on day 1. Beginning 22-36 days after administration, patients undergo surgery.

Biological: Anti-SEMA4D Monoclonal Antibody VX15/2503; Biological: Ipilimumab; Procedure: Surgery

Arm IV (VX15/2503, nivolumab, surgery)

EXPERIMENTAL

Patients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes and nivolumab IV over 60 minutes on day 1. Beginning 22-36 days after administration, patients undergo surgery.

Biological: Anti-SEMA4D Monoclonal Antibody VX15/2503; Biological: Nivolumab; Procedure: Surgery

Interventions

Anti-SEMA4D Monoclonal Antibody VX15/2503 BIOLOGICAL

Given IV

Also known as: moAb VX15/2503, VX15/2503

Arm II (VX15/2503, surgery); Arm III (VX15/2503, ipilimumab, surgery); Arm IV (VX15/2503, nivolumab, surgery)

Ipilimumab BIOLOGICAL

Given IV

Also known as: BMS-734016, MDX-010, MDX-CTLA4, Yervoy

Arm III (VX15/2503, ipilimumab, surgery)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Arm IV (VX15/2503, nivolumab, surgery)

Surgery PROCEDURE

Undergo therapeutic conventional surgery

Arm I (surgery); Arm II (VX15/2503, surgery); Arm III (VX15/2503, ipilimumab, surgery); Arm IV (VX15/2503, nivolumab, surgery)

Eligibility Criteria

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

You may qualify if:

• For patients with pancreatic cancer:
• Stage I-III cytologically or histologically-proven pancreatic adenocarcinoma
• Cancer confirmed to be surgically resectable, with surgery evaluation with planned resection
• Patients may have prior neoadjuvant chemotherapy, but no neoadjuvant chemoradiation
• No cancer chemotherapy treatment 2 weeks prior to day 2 of treatment
• For patients with metastatic colorectal cancer:
• Stage IV histologically-proven colorectal adenocarcinoma
• Liver metastasis confirmed to be surgically resectable, with surgery evaluation and planned resection; may have minimal extrahepatic disease that is determined to be resectable
• Tumor must be confirmed to be microsatellite stable (MSS); if not already reported at a Clinical Laboratory Improvement Act (CLIA)-certified laboratory, we will be able to perform this at Emory University
• No prior immunotherapy
• No cancer chemotherapy treatment 2 weeks prior to day 1 of treatment
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Absolute neutrophil count ≥ 1,500 cells/µL
• Platelets ≥ 100,000/µL
• Hemoglobin ≥ 9.0 g/dL (may receive packed red blood cell \[prbc\] transfusion)

You may not qualify if:

• Poor venous access for study drug administration
• Determined not to be a surgical candidate due to medical co-morbidities
• Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation)
• Prior organ allograft or allogeneic bone marrow transplantation
• Subjects with any active autoimmune disease or history of known or suspected autoimmune disease except for subjects with vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residual hypothyroidism, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• Women who are pregnant or lactating
• Uncontrolled intercurrent illness including, but not limited to, human immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association \[NYHA\] class III or IV), unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study
• Clinical evidence of bleeding diathesis or coagulopathy
• Patients with prior malignancies, including pelvic cancer, are eligible if they have been disease free for \> 5 years; patients with prior in situ carcinomas are eligible provided there was complete removal
• Active bacterial or fungal infections requiring systemic treatment within 7 days of treatment
• Use of other investigational drugs (drugs not marked for any indication) within 28 days or at least 5 half-lives (whichever is longer) before study drug administration
• History of severe hypersensitivity reactions to other monoclonal antibodies
• Non-oncology vaccines within 28 days prior to or after any dose of ipilimumab

Sponsors & Collaborators

• Emory University: lead
• Vaccinex Inc.: collaborator
• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (4)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Colorectal Neoplasms

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Study Officials

• Olatunji Alese, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 11, 2017
• First Posted: December 14, 2017
• Study Start: December 15, 2017
• Primary Completion: October 28, 2021
• Study Completion: October 28, 2021
• Last Updated: March 20, 2024

Record last verified: 2024-03

Locations

US (4)