Melanoma Stage IIIPhase 2NCT06295159
Neoadjuvant and Adjuvant Anti-PD1 or Combinations for Locoregionally Advanced Melanoma
A Phase 2 study testing Nivolumab, Nivolumab + Relatlimab and Ipilimumab in people with Melanoma Stage III and Melanoma Stage IV, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma Stage III, Melanoma Stage IV, Advanced Melanoma
- What is being tested?
- Nivolumab, Nivolumab + Relatlimab and Ipilimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- 17 May 2024to Nov 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
- Requirements for prior systemic therapy for melanoma are as follows:
- Sub-study Part 1: No prior systemic therapy for melanoma (N=30).
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- 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.
- Participants with in-transit or satellite metastases with or without lymph node involvement are allowed if they are considered surgically resectable at Screening by the treating surgical oncologist.
- Participants with distant cutaneous/subcutaneous, soft tissue or nodal metastases with or without regional lymph node involvement are allowed if they are considered potentially surgically resectable and can be biopsied at Screening by the treating surgical oncologist. Elevated LDH is not an exclusion.
- Elevated LDH is not an exclusion.
- Participants are eligible for this study either at presentation for primary melanoma with concurrent regional nodal and/or in-transit or distant metastasis, or at the time of clinically detected nodal, in transit, or distant recurrence.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Adequate organ function within 28 days of Cycle 1 Day 1 (C1D1)
- Participants must provide a sufficient and adequate formalin-fixed paraffin-embedded (FFPE) tumor tissue sample from the most recent biopsy of a tumor lesion, obtained within 90 days from signing informed consent form (ICF). If recent tumor tissue is unavailable or inadequate, a fresh biopsy will be required, unless the principal investigator agrees that it is not safe/feasible.
- Participants must be evaluated by standard-of-care full body imaging studies, the choice of which is decided by the treating physician investigator.
- Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test at screening (within 72 hours of first dose of study medication) in accordance with the standard of care for WOCBP.
- WOCBP must agree to use highly effective contraceptive measures starting with the screening visit through 5 months after the last dose of study treatment. Highly effective contraception is as stipulated in national or local guidelines.
- Male participants with a female partner(s) of childbearing potential must agree to use highly effective contraceptive measures throughout the study starting with the screening visit through 5 months after the last dose of study treatment is received. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.
- Willing and able to comply with the requirements of the protocol.
Who cannot join
- 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.
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- 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.
- Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
- Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) within 14 days or another immunosuppressive medication within 30 days of the first dose of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
- Active autoimmune disease or history of autoimmune disease that required systemic treatment within 2 years before starting treatment, i.e., with use of disease-modifying agents or immunosuppressive drugs.
- History or current evidence of any condition, co-morbidity, therapy, any active infections, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
- Pregnant or breastfeeding or WOCBP who are not willing to employ effective birth control from screening to 5 months after the last dose of study treatment (whichever is later).
- Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to C1D1.
- Uncontrolled infection with human Immunodeficiency virus (HIV). Patients on stable highly active antiretroviral therapy (HAART) with undetectable viral load and normal CD4 counts for at least 6 months prior to study entry are eligible. Serological testing for HIV at screening is not required.
- Known to be positive for hepatitis B virus (HBV) surface antigen, or any other positive test for HBV indicating acute or chronic infection. Patients who are receiving or who have received anti-HBV therapy and have undetectable HBV DNA for at least 6 months prior to study entry are eligible. Serological testing for HBV at screening is not required. Known active co-infection with hepatitis B and hepatitis C or with hepatitis B and hepatitis D is an exclusion.
- Known active hepatitis C virus (HCV) as determined by positive serology and confirmed by polymerase chain reaction (PCR). Patients on or who have received antiretroviral therapy are eligible provided they are virus-free by PCR for at least 6 months prior to study entry. Serological testing for HCV at screening is not required.
- Dependence on total parenteral nutrition.
- Troponin T (TnT) or I (TnI) > 2× institutional ULN. Participants with TnT or TnI levels between > 1 to 2 × ULN will be permitted if repeat levels within 24 hours are ≤ 1 × ULN. If TnT or TnI levels are between >1 to 2 × ULN within 24 hours, the participant must undergo a cardiology consultation and cardiac evaluation and be considered for treatment, based on a favorable benefit/risk assessment by the Investigator. When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible. If TnT or TnI repeat levels beyond 24 hours are < 2 × ULN, the participant must undergo a cardiology consultation and cardiac evaluation and be considered for treatment, based on a favorable benefit-risk assessment by the Investigator.
- Left ventricular ejection fraction (LVEF) assessment with documented LVEF < 50% by either transthoracic echocardiogram (TTE) or multigated acquisition (MUGA) scan (TTE preferred test) within 6 months prior to start of study treatment.
- Participants with a history of myocarditis and/or current diagnosis of myocarditis, regardless of etiology.
- Participants must not have a history of allergy or hypersensitivity to study intervention components.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Ahmad Tarhini, MD, PhD
About this study
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
- Being tested
- Nivolumab, Nivolumab + Relatlimab, Ipilimumab
- Keywords
- Melanoma, Anti-PD1, Locoregionally Advanced Melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo
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 + RelatlimabDrug
Also called Opdualag
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.
IpilimumabDrug
Also called Yervoy
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 group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Nivolumab + Relatlimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 36 Months
Secondary outcomes (6)
Preoperative Radiologic Response Rate
The Preoperative Radiologic Response Rate will be measured utilizing RECIST v.1.1.
Measured: Up to 8 Weeks
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.
Measured: Up to 36 Months
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.
Measured: Up to 36 Months
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.
Measured: Up to 36 Months
Progression Free Survival (PFS)
Progression Free Survival (PFS) will be measured from the date of start of treatment to the investigator-determined date of progression or death due to any cause, whichever occurs first.
Measured: Up to 36 Months
Overall Survival (OS)
Overall Survival (OS) will be measured from the initial date of study registration/randomization to the recorded date of death.
Measured: Up to 36 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2024
- Study start17 May 2024
- Primary completionNov 2028 (estimated)
- Study completionNov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Melanoma Stage IIIStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Ahmad Tarhini, MD, PhD, Principal investigator, Moffitt Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06295159
- Sponsor's protocol ID
- MCC-22574
- Status last verified
- Mar 2026
- First submitted
- 28 Feb 2024
- Last updated
- 1 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant and Adjuvant Anti-PD1 or Combinations for Locoregionally Advanced Melanoma
- ClinicalTrials.gov ID
- NCT06295159
- Acronym / sponsor ID
- MCC-22574
- Conditions
- Melanoma Stage III, Melanoma Stage IV, Advanced Melanoma, Melanoma
- Keywords
- Melanoma, Anti-PD1, Locoregionally Advanced Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 17 May 2024 (actual)
- Primary completion
- Nov 2028 (estimated)
- Study completion
- Nov 2028 (estimated)
- First posted
- 6 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Part 1, Arm A: Nivolumab | Experimental | Drug: NivolumabPD-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. |
| Part 1, Arm B: Nivolumab- Relatlimab-rmbw | Experimental | Drug: Nivolumab + RelatlimabPD-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. |
| Part 1, Arm C: Nivolumab plus ipilimumab | Experimental | Drug: Nivolumab, Drug: IpilimumabPD-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. |
| Part 2, Arm A: Ipilimumab + Nivolumab-Relatimab-rmbw | Experimental | Drug: Nivolumab + Relatlimab, Drug: IpilimumabSystemic 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. |
| Part 2, Arm B1: Triplet Combination Therapy Ipilmumab + Nivolumab-Relatlimab-rmbw | Experimental | Drug: Nivolumab + Relatlimab, Drug: IpilimumabPatients 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. |
| Part 2, Arm B2: Doublet Combination Therapy Nivolumab-Relatlimab-rmbw | Experimental | Drug: Nivolumab + RelatlimabPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- 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).
- Requirements for prior systemic therapy for melanoma are as follows:
Key exclusion criteria (29 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: OpdivoNivolumab 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. | Drug | Part 1, Arm A: Nivolumab, Part 1, Arm C: Nivolumab plus ipilimumab |
| Nivolumab + RelatlimabAlso: OpdualagOpdualag (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. | Drug | 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 |
| IpilimumabAlso: YervoyIpilimumab 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. | Drug | 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 |
Primary outcome
Pathologic Major Response (pMR)
Time frame: Up to 36 Months
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.
6 secondary outcomes
Preoperative Radiologic Response Rate
Time frame: Up to 8 Weeks
Complete Pathologic Response Rate (pCR)
Time frame: Up to 36 Months
Partial Pathologic Response Rate (pPR)
Time frame: Up to 36 Months
Non-Response Pathologic Response Rate (pNR)
Time frame: Up to 36 Months
Progression Free Survival (PFS)
Time frame: Up to 36 Months
Overall Survival (OS)
Time frame: Up to 36 Months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ahmad Tarhini, MD, PhD principal investigator
Moffitt Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab, Nivolumab + Relatlimab and Ipilimumab in people with Melanoma Stage III and Melanoma Stage IV, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lina Moreno (813-745-1060, Lina.Moreno@moffitt.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic Major Response (pMR) (time frame: Up to 36 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2026.