RecruitingPhase 2NCT06295159

Neoadjuvant and Adjuvant Anti-PD1 or Combinations for Locoregionally Advanced Melanoma

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Enrollment

90 participants

Start Date

May 17, 2024

Study Type

INTERVENTIONAL

Conditions

Melanoma Advanced Melanoma Melanoma Stage IV Melanoma Stage III

Summary

The purpose of this study is to determine if neoadjuvant (treatment before surgery) immunotherapy treatment based on tumor biomarkers results in better participant outcomes. Immunotherapy is the treatment of disease by using a person's own immune system. This study is divided into 2 sub-studies/parts designated Part 1 and Part 2 that will enroll in sequence starting with Part 1 followed by Part 2.

Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study is testing immunotherapy approaches — anti-PD1 drugs alone or in combination — given before and after surgery for people with advanced but surgically removable melanoma (skin cancer) that involves nearby lymph nodes or limited spread. The goal is to reduce the chance of cancer coming back. **You may be eligible if...** - You are 18 or older with confirmed melanoma (cutaneous, acral, mucosal, or unknown primary) - Your melanoma is at a locally advanced stage involving regional lymph nodes (specific AJCC 8th edition staging criteria apply) - You meet specific requirements regarding prior systemic therapy depending on which part of the study you join **You may NOT be eligible if...** - Your melanoma has spread extensively to distant organs beyond what the study allows - You have active autoimmune disease that requires systemic treatment - You are pregnant or breastfeeding - You cannot tolerate immunotherapy due to prior severe reactions Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGNivolumab

Nivolumab is a fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1, PCD-1) with immune checkpoint inhibitory and antineoplastic activities. Upon administration, nivolumab binds to and blocks the activation of PD-1, an immunoglobulin superfamily (IgSF) transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), which is overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on antigen-presenting cells (APCs). This results in the activation of T cells and cell-mediated immune responses against tumor cells. Activated PD-1 negatively regulates T-cell activation and plays a key role in tumor evasion from host immunity.

DRUGNivolumab + Relatlimab

Opdualag (Nivolumab and Relatlimab-rmbw) is a combination formulation composed of nivolumab, a human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1, PCD-1), and relatlimab-rmbw, a human IgG4 monoclonal antibody directed against the inhibitor receptor lymphocyte activation gene-3 (LAG-3). Nivolumab binds to and blocks the activation of PD-1 by its ligands programmed cell death ligand 1 (PD-L1), which is overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on antigen-presenting cells (APCs). This prevents PD-1-mediated signaling and PD-1-mediated inhibition of the immune response. Relatlimab binds to LAG-3 on tumor infiltrating lymphocytes (TILs) and prevents LAG-3 binding to major histocompatibility complex (MHC) class II. This prevents LAG-3-mediated signaling and LAG-3-mediated inhibition of the immune response.

DRUGIpilimumab

Ipilimumab is a type of monoclonal antibody and a type of immune checkpoint inhibitor that may block CTLA-4 and help the immune system kill cancer cells. Ipilimumab binds to the protein CTLA-4 to help immune cells kill cancer cells better and is used to treat many different types of cancer. These include cancers that have certain mutations (changes) in genes involved in DNA repair.