Cryoablation+Ipilimumab+Nivolumab in Melanoma

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• Adult patients (age > 18) with unresectable melanoma who have progressed on immune checkpoint inhibitor therapy (pembrolizumab, nivolumab, nivolumab-relatimab, atezolizumab, ipilimumab) and for whom their treating physician plans to initiate dual ICI with ipilimumab and nivolumab. Progression on adjuvant PD-1 inhibition is permitted. PD-1 does not have to be the last therapy received. This is no limited on prior lines of ICI received. There is no wash-out period required from the time of their last therapy.
• Patients are medically eligible for dual checkpoint inhibition (i.e. no untreated/uncontrolled intercurrent medical issue including ongoing immune-related adverse event or need for systemic steroids >10mg PO prednisone or its equivalent, ECOG PS ≤2) with ipilimumab 3mg/kg and nivolumab 1mg/kg by their treating physician
• Must have a tumor amenable to percutaneous image-guided cryoablation based on routine Interventional Radiology criteria.
• Patients must have measurable disease (by RECIST) independent of the lesion to be ablated. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 11 (Measurement of Effect) for evaluation of measurable disease.
• Prior radiation therapy to any site is allowed; with an exception of the target site for planned cryoablation
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
• Life expectancy of greater than 3 months
• Participants must have adequate organ and marrow function as defined below:
• Leukocytes ≥3,000/mcL
• Absolute neutrophil count ≥1,000/mcL
• Platelets ≥75,000/mcL
• Total bilirubin ≤3 institutional upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT) ≤5 × institutional ULN
• CrCL > 30 ml/min
• Known Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. (HIV testing not required at screening).
• For participants with known evidence of known chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. (HBV testing not required at screening).
• Participants with a history of known hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. (HCV testing not required at screening).
• Participants with asymptomatic brain metastases are eligible.
• Participants with new or progressive asymptomatic brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy.
• Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Ability to understand and the willingness to sign a written informed consent document.

You cannot join if

• Lesion to undergo cryoablation cannot have had prior radiation therapy or other locoregional therapy
• Inability to hold systemic anticoagulation prior to cryoablation (if holding anticoagulation is required by the operator)
• Participants who are receiving an investigational agent(s).
• Participants who are progressing on combination ipilimumab/nivolumab as their last line of therapy
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1)
• Patients with symptomatic brain metastasis or LMD
• Participants on > 10mg of oral prednisone or its equivalent
• Participants with uncontrolled intercurrent illness.
• Pregnant women are excluded from this study because immune checkpoint inhibitors have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with immune checkpoint inhibitors, breastfeeding should be discontinued.

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

ipilimumab. A recombinant human immunoglobulin (Ig) G1 monoclonal antibody directed against the human T-cell receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), with immune checkpoint inhibitory and antineoplastic activities. Ipilimumab binds to CTLA4 expressed on T cells and inhibits the CTLA4-mediated downregulation of T-cell activation. This leads to a cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells. CTLA4, an inhibitory receptor and member of the immunoglobulin superfamily, plays a key role in the downregulation of the immune system. NCI Drug Dictionary

nivolumab. 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. NCI Drug Dictionary

Treatments listed in the registry

• Ipilimumab (Drug): Monoclonal antibody administered through intravenous infusion
• Nivolumab (Drug): Monoclonal antibody administered through intravenous infusion
• Cryoablation (Procedure): Procedure of freezing a tumor performed via CT-guidance by interventional radiologist.

Na · Single Group · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• biopsy: Part of the study plan
• blood samples: Part of the study plan
• CT scans: Part of the study plan

Main goals

• Rate of Clinical Benefit (6 months post-1st cryoablation)

Other goals

• Number of Participants with Adverse Events
• Duration of Overall Response
• Progression-Free Survival (PFS)
• Overall Survival (OS)

Planned enrollment: 37 (estimated).

• Massachusetts General Hospital Cancer Center, Boston, Massachusetts

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT05779423
• NCI Drug Dictionary: C2654
• NCI Drug Dictionary: C68814

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Aug 26, 2026. Public record; not medical advice.