Dendritic Cell Therapy after Cryosurgery in Combination with Pembrolizumab in Treating Patients with Stage III-IV Melanoma That Cannot Be Removed by Surgery

Inclusion Criteria

• Histologically or cytologically confirmed diagnosis of unresectable stage III or metastatic melanoma (stage IV) not amenable to curative local therapy
• Lack of response to therapy with a PD-1- or PD-L1-targeting monoclonal antibody (pembrolizumab, nivolumab, etc.) after at least 18 weeks of therapy OR documented progression of disease at any time after initiation of therapy with a PD-1- or PD-L1-targeting monoclonal antibody; NOTE: This treatment could have been at any time prior to registration; if given in the adjuvant setting, progression must have been =< 26 weeks after the last dose of therapy
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Minimum of 3 radiographically apparent lesions such that there is: * Minimum of one lesion in areas that have not been previously irradiated that is considered measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria AND * Minimum of two lesions in areas that have not been previously irradiated that are determined by interventional radiology to be of a size and in a location that a single probe could ablate at least 75% of the lesion; Note: Hepatic lesions measuring =< 3 cm may be treated, as determined by interventional radiology; Note: Brain metastases are not acceptable as lesions defining measurable disease, nor are they candidate lesions for cryoablation
• Adequate venous access for apheresis as assessed by apheresis team; NOTE: If a central venous catheter is required for apheresis, the patient is not eligible
• Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to registration)
• Absolute lymphocyte count >= 500/mm^3 obtained =< 14 days prior to registration
• Platelet count >= 100,000/mm^3 (obtained =< 14 days prior to registration)
• Hemoglobin >= 10 g/dL (obtained =< 14 days prior to registration)
• Total bilirubin =< 1.5 x upper limit of normal (ULN), unless due to Gilbert’s disease (obtained =< 14 days prior to registration)
• Aspartate transaminase (AST/(serum glutamic-oxaloacetic transaminase [SGOT]) and alanine transaminase (ALT/serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (obtained =< 14 days prior to registration)
• Creatinine =< 1.5 x ULN or calculated creatinine clearance >= 60 mL/min for subject with creatinine ˃ 1.5 x institutional ULN (obtained =< 14 days prior to registration)
• Negative serum pregnancy test for persons of childbearing potential =< 7 days prior to registration
• Provide written informed consent
• Willing to return to the enrolling institution for follow-up (during active treatment and active monitoring phase of the study)
• Willing to provide tissue and blood samples for research purposes
• Willing to use adequate contraception while on the study and until 120 days after the last dose of study drug

Exclusion Criteria

• Choroidal melanoma
• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown: * Pregnant persons * Nursing persons
• History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• Active tuberculosis or active, non-infectious pneumonitis
• Evidence of interstitial lung disease
• Active infection requiring the use of systemic antibiotics
• Symptomatic congestive heart failure (New York Heart Association classification III or IV cardiovascular disease, myocardial infarction =< 6 months prior to registration, unstable angina pectoris or cardiac arrhythmia =< 3 months prior to registration, or cardiac arrhythmia
• Currently receiving or have received any other investigational agent considered as a treatment for the primary neoplasm =< 21 days prior to registration
• History of other primary malignancy requiring systemic treatment =< 3 years prior to registration; patients must not be receiving chemotherapy or immunotherapy for another cancer; patients must not have another active malignancy requiring active treatment; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
• Failure to recover from prior side effects of immune checkpoint inhibitor therapy to =< grade 1; NOTE: Patients will not be excluded for adrenal insufficiency or hypothyroidism secondary to immunotherapy provided they are receiving hormonal replacement
• Major surgery =< 4 weeks prior to registration
• Prior chemotherapy, targeted therapy, or radiation therapy =< 2 weeks prior to registration or who has not recovered (i.e. to =< grade 1 or baseline) from an adverse event due to the previously administered therapy
• History of hypersensitivity and anaphylactoid reactions to pneumococcal vaccine or any component of the formulation, including diphtheria toxoid
• Active autoimmune disease such as Crohn’s disease, rheumatoid arthritis, Sjogren's disease, systemic lupus erythematosus, or similar conditions requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease/syndrome difficult to control in the past; EXCEPTIONS (the following are allowed): * Vitiligo or resolved childhood asthma/atopy * Intermittent use of bronchodilators or local steroid injections * Non-immunosuppressive maintenance treatments in the setting of clinically asymptomatic disease (e.g., sulfasalazine for ulcerative colitis) * Hypothyroidism stable on hormone replacement * Diabetes stable with current management * History of positive Coombs test but no evidence of hemolysis * Psoriasis not requiring systemic treatment * Conditions not expected to recur in the absence of an external trigger * Secondary adrenal insufficiency from previous hypophysitis, currently on physiologic replacement steroid dosing only
• Coagulopathy, including the use of therapeutic anticoagulants that cannot be discontinued for the cryoablation procedure; NOTE: Heparin for line patency without detectable lab abnormalities for coagulation will be allowed
• Corticosteroid use =< 14 days prior to registration; NOTE: Patients must be off systemic corticosteroids for at least 2 weeks prior to registration; this includes oral or IV route of administration; patients on chronic corticosteroids for adrenal insufficiency or other reasons may enroll if they receive less than 10 mg/day of prednisone (or equivalent); patients receiving inhaled or intranasal or intra-articular steroids are not excluded
• Active central nervous system (CNS) metastasis; NOTE: Patients with prior brain metastases that are asymptomatic without corticosteroid use and stable or improved >= 90 days after treatment with surgery or radiation are not excluded
• Receipt of a live vaccine =< 30 days prior to registration