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

Part of paid clinical trials in Tampa, Florida.

Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Study ID
NCT06295159
Phase
PHASE2
Status
Recruiting
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Conditions

  • Advanced Melanoma
  • Melanoma
  • Melanoma Stage III
  • Melanoma Stage IV

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Nivolumab — DRUG
    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.
  • Nivolumab + Relatlimab — DRUG
    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.
  • Ipilimumab — DRUG
    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.

Study Details

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.

Key Dates

Start date
May 17, 2024
Status verified
Mar 2026
Primary completion
Nov 30, 2028
Completion
Nov 30, 2028

Study Design

Enrollment
90 participants (estimated)
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Part 1, Arm A: Nivolumab
    PD-L1 positive patients will be given Nivolumab 480 mg I.V. over 30 minutes (-/+ 10 minutes) every 4 weeks (every cycle) for 2 a total of 2 cycles.
  • Experimental: Part 1, Arm B: Nivolumab- Relatlimab-rmbw
    PD-L1 negative patients will be given a combination of Nivolumab 480 mg with Relatlimab 160 mg I.V. over 60 minutes (-/+ 10 minutes) every 4 weeks (every cycle) for a total of 2 cycles.
  • Experimental: Part 1, Arm C: Nivolumab plus ipilimumab
    PD-L1 negative patients will be given 3 mg/kg of Nivolumab plus 1 mg/kg of Ipilimumab I.V. each given over 30 minutes (-/+ 10 minutes) every 4 weeks (every cycle) for a total of 2 cycles.
  • Experimental: Part 2, Arm A: Ipilimumab + Nivolumab-Relatimab-rmbw
    Systemic therapy naïve locoregionally advanced melanoma patients will be given the fixed dose combination of 480 mg of nivolumab with 160 mg of relatlimab I.V. over 60 minutes (-/+ 10 minutes) every 4 weeks (every cycle) for a total of 2 cycles. In addition, a single dose of 1 mg/kg ipilimumab I.V. will be given on C1D1.
  • Experimental: Part 2, Arm B1: Triplet Combination Therapy Ipilmumab + Nivolumab-Relatlimab-rmbw
    Patients with locoregionally advanced melanoma that is refractory to systemic adjuvant therapy will be given the fixed dose combination of 480 mg of nivolumab with 160 mg or relatlimab I.V. over 60 minutes (-/+ 10 minutes) every 4 weeks (every cycle) for a total of 2 cycles. In addition, a single dose of 1 mg/kg ipilimumab I.V. will be given on C1D1.
  • Experimental: Part 2, Arm B2: Doublet Combination Therapy Nivolumab-Relatlimab-rmbw
    Patients with locoregionally advanced melanoma that is refractory to systemic adjuvant therapy will be given the fixed dose combination of 480 mg of nivolumab with 160 mg of relatlimab I.V. over 60 minutes (-/+ 10 minutes) every 4 weeks (every cycle) for a total of 2 cycles.

Primary Outcome Measure

Pathologic Major Response (pMR) [ Time Frame: Up to 36 Months ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Moffitt Cancer CenterTampaFlorida33612
Ahmad Tarhini, MD, PhD (PRINCIPAL_INVESTIGATOR)

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Moffitt Cancer Center· Tampa, FL

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