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

NCT ID: NCT03690986

Last Updated: 2025-07-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-01
• Study Completion Date: 2027-11-30

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.

Detailed Description

PRIMARY OBJECTIVE:

To evaluate the effect of 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 head and neck squamous cell carcinoma.

OUTLINE: Patients are randomized to 1 of 6 groups.

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

GROUP B: 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.

GROUP C: 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.

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

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

GROUP F: Patients undergo standard of care surgery.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A (VX15/2503)

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

Group Type: EXPERIMENTAL

VX15/2503

Intervention Type: BIOLOGICAL

Given IV

Group B (VX15/2503, ipilimumab)

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.

Group Type: EXPERIMENTAL

VX15/2503

Intervention Type: BIOLOGICAL

Given IV

Ipilimumab

Intervention Type: BIOLOGICAL

Given IV

Group C (VX15/2503, nivolumab)

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.

Group Type: EXPERIMENTAL

VX15/2503

Intervention Type: BIOLOGICAL

Given IV

Nivolumab

Intervention Type: BIOLOGICAL

Given IV

Group D (nivolumab)

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

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: BIOLOGICAL

Given IV

Group E (ipilimumab)

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

Group Type: EXPERIMENTAL

Ipilimumab

Intervention Type: BIOLOGICAL

Given IV

Group F (no treatment)

Patients undergo standard of care surgery.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

VX15/2503

Given IV

Intervention Type: BIOLOGICAL

Ipilimumab

Given IV

Intervention Type: BIOLOGICAL

Nivolumab

Given IV

Intervention Type: BIOLOGICAL

Other Intervention Names

moAb VX15/2503; Anti-SEMA4D Monoclonal Antibody VX15/2503; Pepinemab; BMS-734016; MDX-010; MDX-CTLA4; Yervoy; BMS-936558; MDX-1106; NIVO; ONO-4538; Opdivo

Eligibility Criteria

Inclusion Criteria

• 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
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
• Ability to understand and willingness to sign a written informed consent document
• Female subjects of childbearing potential must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) for the duration of study treatment and 3 months after completion
• Male subjects must agree to use adequate contraception (e.g., condoms; abstinence) for the duration of study treatment and 3 months after completion
• Female subjects of childbearing age must have a negative serum pregnancy test at study entry

Exclusion Criteria

• 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
• History of severe hypersensitivity reactions to other monoclonal antibodies
• Non-oncology vaccines within 28 days prior to or after any dose of ipilimumab
• No archival tissue available pre-study treatment, and repeat biopsy not feasible

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vaccinex Inc.

INDUSTRY

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Conor Steuer

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Conor Steuer, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University Hospital Midtown

Atlanta, Georgia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Conor Steuer, MD

Role: CONTACT

csteuer@emory.edu

404-686-1753

Nabil Saba, MD

Role: CONTACT

nfsaba@emory.edu

Facility Contacts

Adedolapo Adedayo, MBBS

Role: primary

adedolapo.adedayo@emory.edu

404-686-3925

Other Identifiers

NCI-2018-01263

Identifier Type: REGISTRY

Identifier Source: secondary_id

Winship4402-18

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00103534

Identifier Type: -

Identifier Source: org_study_id