VX15/2503 in Combination With Ipilimumab or Nivolumab in Patients With Head and Neck Cancer

NCT03690986 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: IRB00103534NCI-2018-01263Winship4402-18
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies how well anti-semaphorin 4D (SEMA4D) monoclonal antibody VX15/2503 (VX15/2503) with or without ipilimumab and/or nivolumab work in treating patients with stage I-IVA head and neck squamous cell cancer. Monoclonal antibodies, such as VX15/2503, ipilimumab, and nivolumab, may interfere with the ability of tumor cells to grow and spread.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Outcome Measures

Primary Outcomes (3)

• Change in immune profile in the tumor microenvironment

  Specimens from surgical resection will be collected under the guidance of the collaborating pathologist and tissue procurement staff at the time of surgery to capture tissue in excess of that needed for clinical staging and diagnostic purposes. Tumor specimens will be fixed in 10% formalin, embedded in paraffin and biomarkers related to activated HNSCC stroma will be assessed via immunohistochemical analysis.

  Baseline up to 4-8 weeks after surgery

• Change in circulating percentage of immune suppressor subsets in peripheral blood

  Blood samples will be collected and peripheral blood mononuclear cells will be isolated from these samples and stored in -80°C freezers until analysis. Multi-parameter flow cytometry will be utilized to phenotype immune effector cells. The impact of treatment on the circulating percentage of immune suppressor subsets that may serve as predictors of response to immune checkpoint inhibition. All data will be expressed as the percentage of total circulating peripheral blood cells with each respective phenotype.

  Baseline up to 4-8 weeks after surgery

• Phenotypic shifts in T lymphocyte subsets in peripheral blood

  Blood samples will be collected and peripheral blood mononuclear cells will be isolated from these samples and stored in -80°C freezers until analysis. Blood will be analyzed by multi-parameter flow cytometry to identify systemic phenotypic shifts mediated by VX15/2503 in combination with immune checkpoint inhibition.

  Baseline up to 4-8 weeks after surgery

Secondary Outcomes (1)

• Incidence of adverse events assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  Up to 4-8 weeks after surgery

Study Arms (6)

Group A (VX15/2503)

EXPERIMENTAL

Patients receive VX15/2503 IV over 60 minutes on day 1. Beginning days 17-36, patients undergo standard of care surgery.

Biological: VX15/2503

Group B (VX15/2503, ipilimumab)

EXPERIMENTAL

Patients receive VX15/2503 IV over 60 minutes and ipilimumab IV over 90 minutes on day 1. Beginning days 17-36, patients undergo standard of care surgery.

Biological: VX15/2503; Biological: Ipilimumab

Group C (VX15/2503, nivolumab)

EXPERIMENTAL

Patients receive VX15/2503 IV over 60 minutes and nivolumab IV over 60 minutes on day 1. Beginning days 17-36, patients undergo standard of care surgery.

Biological: VX15/2503; Biological: Nivolumab

Group D (nivolumab)

EXPERIMENTAL

Patients receive nivolumab IV over 60 minutes on day 1. Beginning days 17-36, patients undergo standard of care surgery.

Biological: Nivolumab

Group E (ipilimumab)

EXPERIMENTAL

Patients receive ipilimumab IV over 90 minutes on day 1. Beginning days 17-36, patients undergo standard of care surgery.

Biological: Ipilimumab

Group F (no treatment)

NO INTERVENTION

Patients undergo standard of care surgery.

Interventions

VX15/2503 BIOLOGICAL

Given IV

Also known as: moAb VX15/2503, Anti-SEMA4D Monoclonal Antibody VX15/2503, Pepinemab

Group A (VX15/2503); Group B (VX15/2503, ipilimumab); Group C (VX15/2503, nivolumab)

Ipilimumab BIOLOGICAL

Given IV

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

Group B (VX15/2503, ipilimumab); Group E (ipilimumab)

Nivolumab BIOLOGICAL

Given IV

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

Group C (VX15/2503, nivolumab); Group D (nivolumab)

Eligibility Criteria

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

You may qualify if:

• Stage I-IVA cytologically or histologically-proven head and neck squamous cell carcinoma (HNSCC), p16 positive and negative allowed
• Oropharyngeal tumors must have p16 testing done
• Cancer confirmed to be surgically resectable, with surgery evaluation with planned resection
• Archival tissue prior to treatment available from at most 6 months prior to study enrollment. Otherwise new pre-treatment biopsy mandatory
• No prior treatment for HNSCC
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Absolute neutrophil count ≥ 1,500 cells/µL
• Platelets ≥ 100,000/µL
• Hemoglobin ≥ 9.0g/dL (may receive packed red blood cell \[prbc\] transfusion)
• Total bilirubin ≤ 1.5 x the upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
• Albumin ≥ 3.0 g/dL
• Serum creatinine ≤ 1.5 x ULN
• Calculated creatinine clearance of ≤ 50 mL/min
• International normalized ratio (INR) ≤ 1.5. Anticoagulation is allowed only with low molecular weight heparin (LMWH). Patient receiving LMW heparin on stable therapeutic dose for more than 2 weeks or with factor Xa level \< 1.1 units/mL (U/mL) are allowed on the trial

You may not qualify if:

• Poor venous access for study drug administration
• Nasopharynx cancer, cancer of unknown primary, sinonasal cancer
• 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 due to autoimmune condition only requiring hormone replacement, 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
• Prior invasive malignancy (except non-melanomatous skin cancer, low or intermediate risk prostate cancer, or in situ carcinoma fully resected) unless disease free for a minimum of one year
• Patients that have had prior treatment for HNSCC are not eligible
• 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

Sponsors & Collaborators

• Emory University: lead
• Vaccinex Inc.: collaborator

Study Sites (1)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

pepinemab; Ipilimumab; CTLA-4 Antigen; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

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

• Conor Steuer, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Conor Steuer, MD

CONTACT

404-686-1753; csteuer@emory.edu

Nabil Saba, MD

CONTACT

nfsaba@emory.edu

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: September 28, 2018
• First Posted: October 1, 2018
• Study Start: November 1, 2018
• Primary Completion (Estimated): June 4, 2026
• Study Completion (Estimated): November 30, 2027
• Last Updated: July 23, 2025

Record last verified: 2025-06

Locations

US (1)