Clinical Trials /

VX15/2503 With or Without Ipilimumab and/or Nivolumab in Patients With Resectable Stage IIIB-D Melanoma

NCT03769155

Description:

This pilot phase I trial studies how well VX15/2503 (pepinemab) with or without ipilimumab and/or nivolumab work in treating participants with stage IIIB-D melanoma that can be removed by surgery. Monoclonal antibodies, such as VX15/2503, ipilimumab, and nivolumab may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: VX15/2503 With or Without Ipilimumab and/or Nivolumab in Patients With Resectable Stage IIIB-D Melanoma
  • Official Title: Pilot Integrated Biomarker Study of VX15/2503 in Combination With Ipilimumab or Nivolumab in Patients With Resectable Metastatic Melanoma

Clinical Trial IDs

  • ORG STUDY ID: IRB00104273
  • SECONDARY ID: NCI-2018-01229
  • SECONDARY ID: Winship4400-18
  • NCT ID: NCT03769155

Conditions

  • Pathologic Stage IIIB Cutaneous Melanoma AJCC v8
  • Pathologic Stage IIIC Cutaneous Melanoma AJCC v8
  • Pathologic Stage IIID Cutaneous Melanoma AJCC v8

Interventions

DrugSynonymsArms
IpilimumabBMS-734016, MDX-010, MDX-CTLA4, YervoyB (VX15/2503, ipilimumab, surgery)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoA (VX15/2503, nivolumab, surgery)
VX15/2503moAb VX15/2503, PepinemabA (VX15/2503, nivolumab, surgery)

Purpose

This pilot phase I trial studies how well VX15/2503 (pepinemab) with or without ipilimumab and/or nivolumab work in treating participants with stage IIIB-D melanoma that can be removed by surgery. Monoclonal antibodies, such as VX15/2503, ipilimumab, and nivolumab may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Evaluate the effect of VX15/2503 (pepinemab) in combination with immune checkpoint
      inhibitors on T cell infiltrate into the tumor microenvironment in involved and uninvolved
      lymph nodes and peripheral blood.

      SECONDARY OBJECTIVES:

      I. Evaluate the effect of VX15/2503 in combination with immune checkpoint inhibitors on the
      immune profile of involved and uninvolved lymph nodes and peripheral blood.

      II. Assess safety and tolerability of profile and tolerability of single agent VX15/2503 to
      the combination of VX15/2503 and immune checkpoint inhibitors in patients with resectable
      metastatic melanoma.

      III. Document pathologic response rates of single agent VX15/2503 and combination VX15/2503
      and immune checkpoint inhibitors in patients with resectable melanoma.

      IV. Compare pathologic response to radiographic response using Response Evaluation Criteria
      in Solid Tumors (RECIST) criteria in patients receiving single agent VX15/2503 and
      combination VX15/2503 and immune checkpoint inhibitors in patients with resectable melanoma.

      OUTLINE: Participants are assigned to 1 of 5 arms.

      ARM I: Participants receive VX15/2503 intravenously (IV) over 60 minutes and nivolumab IV
      over 30 minutes on days 1 and 21 and undergo surgery between days 35-49.

      ARM II: Participants receive VX15/2503 IV over 60 minutes and ipilimumab IV over 30 minutes
      on days 1 and 21 and undergo surgery between days 35-49.

      ARM III: Participants receive VX15/2503 IV over 60 minutes, nivolumab IV over 30 minutes, and
      ipilimumab IV over 30 minutes on days 1 and 21 and undergo between days 35-49.

      ARM IV: Participants receive VX15/2503 IV over 60 minutes on days 1 and 21 and undergo
      between days 35-49.

      ARM V: Participants undergo surgery.

      After completion of study treatment, participants are followed up at 90 days, every 12 weeks
      for 2 years, every 6 months for 3 years, then annually up to 10 years.
    

Trial Arms

NameTypeDescriptionInterventions
A (VX15/2503, nivolumab, surgery)ExperimentalParticipants receive VX15/2503 (pepinemab) IV over 60 minutes and nivolumab IV over 30 minutes on days 1 and 21 and undergo surgery between days 35-49.
  • Nivolumab
  • VX15/2503
B (VX15/2503, ipilimumab, surgery)ExperimentalParticipants receive VX15/2503 (pepinemab) IV over 60 minutes and ipilimumab IV over 30 minutes on days 1 and 21 and undergo surgery between days 35-49.
  • Ipilimumab
  • VX15/2503
C (VX15/2503, nivolumab, ipilimumab, surgery)ExperimentalParticipants receive VX15/2503 (pepinemab) IV over 60 minutes, nivolumab IV over 30 minutes, and ipilimumab IV over 30 minutes on days 1 and 21 and undergo between days 35-49.
  • Ipilimumab
  • Nivolumab
  • VX15/2503
D (VX15/2503, surgery)ExperimentalParticipants receive VX15/2503 (pepinemab) IV over 60 minutes on days 1 and 21 and undergo between days 35-49.
  • VX15/2503
E (surgery)Active ComparatorParticipants undergo surgery.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Stage IIIB, IIIC, IIID histologically-proven melanoma.
    
                   -  Cancer confirmed to be surgically resectable, with surgery evaluation with
                      planned prior to resection.
    
                   -  No prior immunotherapy with cytotoxic T-lymphocyte associated protein-4 (CTLA-4),
                      anti programmed cell death-1 (PD-1) or VX15/2503. Prior interferon (at least 1
                      year prior to consent) will be allowed.
    
              -  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 cells [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 OR calculated creatinine clearance of ≥ 50 mL/min using
                 Cockcroft-Gault formula.
    
              -  International normalized ration (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 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 5 months after last dose of study treatment.
    
              -  Male subjects must agree to use adequate contraception (e.g., condoms; abstinence) for
                 the duration of study treatment and 7 months after last dose of study treatment.
    
              -  Female subjects of childbearing age must have a negative serum pregnancy test at study
                 entry.
    
            Exclusion Criteria:
    
              -  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 active or history of immune mediated pneumonitis, colitis, hepatitis,
                 endocrinopathy, nephritis, or skin reactions as these patients may be at increased
                 risk for developing immune therapy-induced exacerbation or recurrence of their immune
                 mediated disease, potentially delaying surgery.
    
              -  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 (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 non-melanoma skin cancers and 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.
    
              -  Prisoners and subjects who are compulsory detained.
    
              -  Patients with rapidly progressive disease.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Biomarker parameter analysis: extent of cluster of differentiation 8 (CD8)+ T cell infiltration between experimental groups following treatment
    Time Frame:Up to 10 years after study start
    Safety Issue:
    Description:The two-sample t-test will be used to compare the change in CD8+ T cell infiltration after treatment between each experimental group (Cohort A, B, C, and D) and the control group (cohort E), respectively.

    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 8 weeks after surgery
    Safety Issue:
    Description:Descriptive statistics for worst grade of each laboratory parameter by the NCI CTCAE scale version 4.0 at baseline and follow-up will be presented.
    Measure:Response rate
    Time Frame:Up to 10 years after study start
    Safety Issue:
    Description:For participants to be considered evaluable for efficacy, they must have completed the treatment and have a baseline tumor assessment. Response rate will be calculated as proportion (responders/total participants).
    Measure:Overall survival (OS)
    Time Frame:Assessed up to 10 years after study start
    Safety Issue:
    Description:For overall survival, death from any cause will be defined as the event.
    Measure:Progression-free survival (PFS)
    Time Frame:Assessed up to 10 years after study start
    Safety Issue:
    Description:Progression or death from any cause will be defined as the event.

    Details

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

    Last Updated