Clinical Trials /

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

NCT03690986

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: VX15/2503 in Combination With Ipilimumab or Nivolumab in Patients With Head and Neck Cancer
  • Official Title: Integrated Pilot Biomarker Trial of VX15/2503 in Combination With Ipilimumab or Nivolumab in Patients With Head and Neck Cancer

Clinical Trial IDs

  • ORG STUDY ID: IRB00103534
  • SECONDARY ID: NCI-2018-01263
  • SECONDARY ID: Winship4402-18
  • NCT ID: NCT03690986

Conditions

  • Squamous Cell Carcinoma of the Head and Neck

Interventions

DrugSynonymsArms
VX15/2503moAb VX15/2503, Anti-SEMA4D Monoclonal Antibody VX15/2503, PepinemabGroup A (VX15/2503)
IpilimumabBMS-734016, MDX-010, MDX-CTLA4, YervoyGroup B (VX15/2503, ipilimumab)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoGroup C (VX15/2503, nivolumab)

Purpose

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 participants 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: Participants are randomized to 1 of 6 groups.

      GROUP A: Participants receive VX15/2503 intravenously (IV) over 60 minutes on day 1.
      Beginning days 22-36, participants undergo standard of care surgery.

      GROUP B: Participants receive VX15/2503 IV over 60 minutes and ipilimumab IV over 90 minutes
      on day 1. Beginning days 22-36, participants undergo standard of care surgery.

      GROUP C: Participants receive VX15/2503 IV over 60 minutes and nivolumab IV over 60 minutes
      on day 1. Beginning days 22-36, participants undergo standard of care surgery.

      GROUP D: Participants receive nivolumab IV over 60 minutes on day 1. Beginning days 22-36,
      participants undergo standard of care surgery.

      GROUP E: Participants receive ipilimumab IV over 90 minutes on day 1. Beginning days 22-36,
      participants undergo standard of care surgery.

      GROUP F: Participants undergo standard of care surgery.
    

Trial Arms

NameTypeDescriptionInterventions
Group A (VX15/2503)ExperimentalParticipants receive VX15/2503 IV over 60 minutes on day 1. Beginning days 22-36, participants undergo standard of care surgery.
  • VX15/2503
Group B (VX15/2503, ipilimumab)ExperimentalParticipants receive VX15/2503 IV over 60 minutes and ipilimumab IV over 90 minutes on day 1. Beginning days 22-36, participants undergo standard of care surgery.
  • VX15/2503
  • Ipilimumab
Group C (VX15/2503, nivolumab)ExperimentalParticipants receive VX15/2503 IV over 60 minutes and nivolumab IV over 60 minutes on day 1. Beginning days 22-36, participants undergo standard of care surgery.
  • VX15/2503
  • Nivolumab
Group D (nivolumab)ExperimentalParticipants receive nivolumab IV over 60 minutes on day 1. Beginning days 22-36, participants undergo standard of care surgery.
  • Nivolumab
Group E (ipilimumab)ExperimentalParticipants receive ipilimumab IV over 90 minutes on day 1. Beginning days 22-36, participants undergo standard of care surgery.
  • Ipilimumab
Group F (no treatment)No InterventionParticipants undergo standard of care surgery.

    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
    
              -  Patients with prior malignancies are eligible if they have been disease free for > 5
                 years. Patients with prior in situ carcinomas are eligible provided there was complete
                 removal. 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
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Change in immune profile in the tumor microenvironment
    Time Frame:Baseline up to 4-8 weeks after surgery
    Safety Issue:
    Description: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.

    Secondary Outcome Measures

    Measure:Incidence of adverse events assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
    Time Frame:Up to 4-8 weeks after surgery
    Safety Issue:
    Description:Adverse events will be classified using MedDRA System Organ Classes and Preferred Terms. Furthermore, serious adverse events, adverse events (AEs) with a severity grade of 3 or above using NCI CTCAE version 4.0, AEs deemed related to study drug, AEs leading to discontinuation of study drug, and AEs leading to death will also be summarized in preferred term by system organ class and listed on an individual subject basis.

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Emory University

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