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

NCT03769155 | Active Not Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: IRB00104273NCI-2018-01229Winship4400-18P30CA138292
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Biomarker parameter analysis: extent of cluster of differentiation 8 (CD8)+ T cell infiltration between experimental groups following treatment

  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.

  Up to 10 years after study start

Secondary Outcomes (4)

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

  Up to 8 weeks after surgery

• Response rate

  Up to 10 years after study start

• Overall survival (OS)

  Assessed up to 10 years after study start

• Progression-free survival (PFS)

  Assessed up to 10 years after study start

Study Arms (5)

A (VX15/2503, nivolumab, surgery)

EXPERIMENTAL

Participants 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.

Biological: Nivolumab; Biological: VX15/2503; Procedure: Surgery

B (VX15/2503, ipilimumab, surgery)

EXPERIMENTAL

Participants 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.

Biological: Ipilimumab; Biological: VX15/2503; Procedure: Surgery

C (VX15/2503, nivolumab, ipilimumab, surgery)

EXPERIMENTAL

Participants 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.

Biological: Ipilimumab; Biological: Nivolumab; Biological: VX15/2503; Procedure: Surgery

D (nivolumab, surgery)

EXPERIMENTAL

Participants receive nivolumab IV over 30 minutes on days 1 and 21 and undergo between days 35-49.

Biological: Nivolumab; Procedure: Surgery

E (surgery)

ACTIVE COMPARATOR

Participants undergo surgery.

Procedure: Surgery

Interventions

Ipilimumab BIOLOGICAL

Given IV

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

B (VX15/2503, ipilimumab, surgery); C (VX15/2503, nivolumab, ipilimumab, surgery)

Nivolumab BIOLOGICAL

Given IV

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

A (VX15/2503, nivolumab, surgery); C (VX15/2503, nivolumab, ipilimumab, surgery); D (nivolumab, surgery)

VX15/2503 BIOLOGICAL

Given IV

Also known as: moAb VX15/2503, Pepinemab

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

Surgery PROCEDURE

Undergo therapeutic conventional surgery

A (VX15/2503, nivolumab, surgery); B (VX15/2503, ipilimumab, surgery); C (VX15/2503, nivolumab, ipilimumab, surgery); D (nivolumab, surgery); E (surgery)

Eligibility Criteria

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

You may qualify if:

• 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 (at least one highly effective method and one additional method of birth control at the same time or complete abstinence) prior to study entry, for the duration of study treatment and 5 months after last dose of study treatment.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Interventions

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

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

• Michael Lowe, MD, MA

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON 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 6, 2018
• First Posted: December 7, 2018
• Study Start: December 13, 2018
• Primary Completion: December 15, 2023
• Study Completion (Estimated): December 15, 2032
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (1)