Pilot Study of Nivolumab w/Ipilimumab or Relatlimab in Surgically Resectable Melanoma Brain Metastases

Summary

The purpose of this pilot study is to determine the safety and feasibility of giving a single dose of Nivolumab with Ipilimumab or Relatlimab in participants with brain metastases from melanoma who can undergo surgery for removal of their brain metastases 7- 10 days after receiving the study drug.

Conditions

• Metastatic Melanoma
• Metastasis to Brain

Interventions

DRUG

Nivolumab

Nivolumab is a monoclonal antibody o PD-1 protein, which is normally express on the surface of activated T cells. The interaction of PD-1 with its ligand (PD-L1) on T cells decreases their cytotoxic activity, helping protect normal cells in the setting of chronic inflammation. Tumor cells can utilize mechanisms to evade T cell mediated cytotoxicity by expressing PD-L1 on their surface or on the surface of T cells. Nivo, by blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2, allows T cells to remain active.

DRUG

Ipilimumab

Ipilimumab is a recombinant, human antibody to CTLA-4.\[18-20\] CTLA-4 regulates T cell activation by binding with CD80 or CD86 with higher affinity than CD28, resulting in blockage of the co-stimulation signal and preventing further T cell activation. Blockade of CTLA-4 results in further T cell activation.

DRUG

Nivolumab + Relatlimab

Opdualag (Nivolumab and Relatlimab-rmbw) is a human monoclonal antibody to LAG-3, currently under investigation.\[6\] Relatlimab is an antibody (IgG4 isotype) that has a stabilizing hinge mutation for attenuated Fc receptor binding to decrease or get rid of the possibility of antibody-mediated and/or complement-mediated target cell killing. Rela binds to an epitope on LAG-3 with high affinity and specificity, with subsequent blockade of LAG-3 and its interaction with its ligand, MHC class II. This antibody displays compelling in vitro functional activity in reversing LAG-3 that facilitates inhibition of an antigen-specific murine T cell hybridoma overexpressing human LAG-3 . Relatlimab was also shown to improve the activation of human T cells in superantigen stimulation assays when added either alone or in combination with Nivolumab.

PROCEDURE

Standard of Care Craniotomy

Participants will undergo craniotomy for surgical resection of melanoma brain metastases.

Sponsors & Collaborators

• Bristol-Myers Squibb

  collaborator INDUSTRY

• H. Lee Moffitt Cancer Center and Research Institute

  lead OTHER

Principal Investigators

• Peter Forsyth, MD · Moffitt Cancer Center

• Yolanda Pina, MD · Moffitt Cancer Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-06-06

Primary Completion

2024-06-07

Completion

2024-08-20

FDA Drug

Yes

Countries

• United States

Study Locations