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

ConditionsMelanoma Stage IIIMelanoma Stage IVAdvanced MelanomaMelanoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorH. Lee Moffitt Cancer Center and Research Institute

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

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. In Part 2, Part 2 Cohort A and Part 2 Cohort B will enroll simultaneously. Inclusion criteria apply to Part 1 and Part 2 unless otherwise specified.

Voluntarily agree to participate by giving signed, dated, and written informed consent prior to any study-specific procedures.

18 years of age or older

Histologic diagnosis of melanoma (cutaneous, acral, mucosal or unknown primary) belonging to the following American Joint Committee on Cancer (AJCC) 8th edition TNM stages (Tx or T1-4) and (N1b, N1c, N2b, N2c, N3b or N3c) and/or (M1a).

Disqualifiers

Pregnancy or lactation.

Treatment with another investigational drug or other systemic intervention for melanoma within 4 weeks of initiation of study drugs. Patients must not have radiotherapy within the preceding 2 weeks. Patients must have recovered from adverse events due to agents administered more than 4 weeks earlier.

Participants must be at least 4 weeks from major surgery and have fully recovered from any effects of surgery and be free of significant detectable infection.

Ocular or uveal melanoma.

Trial design

Design model

Sequential

Treatments tested in this trial

  • 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.

Treatment groups

90 Participants
are divided into 6 treatment groups

6

Treatment groups

See each treatment group below.

Group A: Part 1, Arm A: NivolumabExperimental treatment 1 intervention
Group B: Part 1, Arm B: Nivolumab- Relatlimab-rmbwExperimental treatment 1 intervention
Group C: Part 1, Arm C: Nivolumab plus ipilimumabExperimental treatment 2 interventions
Group D: Part 2, Arm A: Ipilimumab + Nivolumab-Relatimab-rmbwExperimental treatment 2 interventions
Group E: Part 2, Arm B1: Triplet Combination Therapy Ipilmumab + Nivolumab-Relatlimab-rmbwExperimental treatment 2 interventions
Group F: Part 2, Arm B2: Doublet Combination Therapy Nivolumab-Relatlimab-rmbwExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Pathologic Major Response (pMR)

The pathologic response rate will be measured by evaluation of the residual viable tumor (RVT). Pathologic Major Response (pMR) is defined as near complete response (pCR) measured as ≤10% RVT + complete response (pCR) measured as 0% RVT.

Time frame
Up to 36 Months

Secondary outcomes

1

Preoperative Radiologic Response Rate

The Preoperative Radiologic Response Rate will be measured utilizing RECIST v.1.1.

Time frame
Up to 8 Weeks
2

Complete Pathologic Response Rate (pCR)

The pathologic response rate will be measured by evaluation of the residual viable tumor (RVT). Pathologic Complete Response (pCR) is defined as 0% RVT.

Time frame
Up to 36 Months
3

Partial Pathologic Response Rate (pPR)

The pathologic response rate will be measured by evaluation of the residual viable tumor (RVT). Pathologic Partial Response (pPR) is defined as 10-50% RVT.

Time frame
Up to 36 Months
4

Non-Response Pathologic Response Rate (pNR)

The pathologic response rate will be measured by evaluation of the residual viable tumor (RVT). Pathologic Non-Response (pNR) is defined as 50-100% RVT.

Time frame
Up to 36 Months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

H. Lee Moffitt Cancer Center and Research Institute

Lead sponsor

Bristol-Myers Squibb

Collaborator

Source ClinicalTrials.gov
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