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

NCT06295159 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MCC-22574
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Melanoma Stage III; Melanoma Stage IV; Advanced Melanoma; Melanoma

Keywords

Melanoma; Anti-PD1; Locoregionally Advanced Melanoma

Outcome Measures

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.

  Up to 36 Months

Secondary Outcomes (6)

• Preoperative Radiologic Response Rate

  Up to 8 Weeks

• Complete Pathologic Response Rate (pCR)

  Up to 36 Months

• Partial Pathologic Response Rate (pPR)

  Up to 36 Months

• Non-Response Pathologic Response Rate (pNR)

  Up to 36 Months

• Progression Free Survival (PFS)

  Up to 36 Months

Study Arms (6)

Part 1, Arm A: Nivolumab

EXPERIMENTAL

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.

Drug: Nivolumab

Part 1, Arm B: Nivolumab- Relatlimab-rmbw

EXPERIMENTAL

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.

Drug: Nivolumab + Relatlimab

Part 1, Arm C: Nivolumab plus ipilimumab

EXPERIMENTAL

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.

Drug: Nivolumab; Drug: Ipilimumab

Part 2, Arm A: Ipilimumab + Nivolumab-Relatimab-rmbw

EXPERIMENTAL

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.

Drug: Nivolumab + Relatlimab; Drug: Ipilimumab

Part 2, Arm B1: Triplet Combination Therapy Ipilmumab + Nivolumab-Relatlimab-rmbw

EXPERIMENTAL

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.

Drug: Nivolumab + Relatlimab; Drug: Ipilimumab

Part 2, Arm B2: Doublet Combination Therapy Nivolumab-Relatlimab-rmbw

EXPERIMENTAL

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.

Drug: Nivolumab + Relatlimab

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.

Also known as: Opdivo

Part 1, Arm A: Nivolumab; Part 1, Arm C: Nivolumab plus ipilimumab

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.

Also known as: Opdualag

Part 1, Arm B: Nivolumab- Relatlimab-rmbw; Part 2, Arm A: Ipilimumab + Nivolumab-Relatimab-rmbw; Part 2, Arm B1: Triplet Combination Therapy Ipilmumab + Nivolumab-Relatlimab-rmbw; Part 2, Arm B2: Doublet Combination Therapy Nivolumab-Relatlimab-rmbw

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.

Also known as: Yervoy

Part 1, Arm C: Nivolumab plus ipilimumab; Part 2, Arm A: Ipilimumab + Nivolumab-Relatimab-rmbw; Part 2, Arm B1: Triplet Combination Therapy Ipilmumab + Nivolumab-Relatlimab-rmbw

Eligibility Criteria

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

You may qualify if:

• Voluntarily agree to participate by giving signed, dated, and written informed consent prior to any study-specific procedures.
• 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).
• Requirements for prior systemic therapy for melanoma are as follows:
• Sub-study Part 1: No prior systemic therapy for melanoma (N=30).
• Sub-study Part 2 Cohort A: No prior systemic therapy for melanoma (N=20)
• Sub-study Part 2 Cohort B: Locoregionally advanced melanoma that is refractory to systemic adjuvant therapy (anti-PD1-based or BRAF-MEK inhibitors) (N=40).
• This excludes patients who previously received adjuvant or neoadjuvant anti-PD1 plus anti-LAG3 or anti-PD1 plus anti-CTLA4.
• Participants who experienced progression or recurrence after anti-PD1 as monotherapy or other combinations or after BRAF-MEK inhibition would be eligible.
• Participants who have previously experienced prior high-grade (grade 3 or 4 by CTCAE criteria) immune related adverse events with immune checkpoint inhibitors are not eligible.
• Must be considered surgically operable and may present as any of the following groups:
• Primary melanoma with clinically apparent regional lymph node metastases, confirmed by pathological diagnosis.
• Clinically detected recurrence of melanoma at regional lymph node basin(s), confirmed by pathological diagnosis.
• Clinically or histologically detected primary melanoma involving multiple regional nodal groups, confirmed by pathological diagnosis.
• Clinically detected single site of nodal metastatic melanoma arising from an unknown primary, confirmed by pathological diagnosis.

You may not qualify if:

• 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.
• Bowel obstruction or impending bowel obstruction within the past 3 months.
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure or serious uncontrolled cardiac arrhythmia requiring medication.
• Active or history of brain metastases or leptomeningeal metastases.
• Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to the first dose of study treatment, i.e., patients with a history of prior malignancy are eligible if treatment was completed at least 2 years before the first dose of study treatment and the patient has no evidence of disease. Participants with history of prior early-stage basal/squamous cell skin cancer, low-risk prostate cancer eligible for active surveillance or noninvasive or in situ cancers who have undergone definitive treatment at any time are also eligible.
• Treatment with one of the following classes of drugs within the delineated time window prior to C1D1:
• Cytotoxic, targeted therapy or other investigational therapy within 3 weeks.
• mAbs, antibody-drug conjugates, radioimmunoconjugates, or similar therapy, within 4 weeks, or 5 half-lives, whichever is shorter.
• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine or booster \< 7 days before C1D1. For vaccines requiring more than 1 dose, the full series should be completed prior to C1D1, when feasible. Booster shot not required but also must be administered \> 7 days from C1D1 or \> 7 days from future cycle on study.
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
• Any evidence of current interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or non-infectious pneumonitis requiring high-dose glucocorticoids.
• History of allogeneic organ transplant.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Related Links

• Moffitt Cancer Center Clinical Trials Website

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab; relatlimab; Opdualag; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ahmad Tarhini, MD, PhD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lina Moreno

CONTACT

813-745-1060; Lina.Moreno@moffitt.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2024
• First Posted: March 6, 2024
• Study Start: May 17, 2024
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: April 1, 2026

Record last verified: 2026-03

Locations

US (1)