Ipilimumab and Nivolumab for the Treatment of Stage III-IV Unresectable Metastatic Melanoma

Exclusion Criteria

• •Metastatic sites that drain lymphatic fluid into nodal beds which are not amenable to lymphatic infusion
• •* Sites of metastases limited only to the head and neck
• •* Sites of metastatic disease limited to the lungs and/or hilar lymph nodes
• •Metastatic uveal 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
• •* Persons of childbearing potential who are unwilling to employ adequate contraception
• •* Persons expecting to conceive or father children during the study or within 180 days (6 months) after the last treatment on this study
• •Active central nervous system (CNS) metastases not previously treated
• •* NOTE: patients with history of previously treated CNS metastases, not demonstrating evidence of progression for at least 12 weeks will be allowed
• •Any of the following prior therapies:
• •* Allogeneic hematopoietic stem cell transplantation (HSCT)
• •* Solid organ transplantation
• •Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• •Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy.
• •* NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
• •Active autoimmune disease requiring systemic treatment \< 2 years prior to registration, documented history of severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents with use of disease modifying agents, corticosteroids or immunosuppressive drugs. NOTE: Exceptions are allowed for the following conditions:
• •* Vitiligo
• •* Resolved childhood asthma/atopy
• •* Intermittent use of bronchodilators or inhaled steroids
• •* Daily steroids at dose of =\< 10 mg of prednisone (or equivalent)
• •* Local steroid injections
• •* Stable hypothyroidism on replacement therapy
• •* Stable diabetes mellitus on therapy (with or without insulin)
• •* Sjogren's syndrome
• •* Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) which is not considered a form of systemic treatment and is allowed
• •Uncontrolled intercurrent illness including, but not limited to:
• •* Ongoing or active infection requiring systemic therapy
• •* Interstitial lung disease
• •* Serious, chronic gastrointestinal conditions associated with diarrhea (e.g., Crohn's disease or others)
• •* Known history of hepatitis B (i.e., known positive hepatitis B virus (HBV) surface antigen (HBsAg) reactive)
• •* Known active hepatitis C (i.e., positive for hepatitis C virus (HCV) ribonucleic acid (RNA) detected by polymerase chain reaction (PCR))
• •* Known active tuberculosis (TB)
• •* Symptomatic congestive heart failure
• •* Unstable angina pectoris
• •* Unstable cardiac arrhythmia or
• •* Psychiatric illness/social situations that would limit compliance with study requirements (e.g., known substance abuse)
• •Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• •History of severe hypersensitivity reactions to other monoclonal antibodies or known hypersensitivity to the study intervention or its excipients, indocyanine green (ICG) dye or iodine
• •Prior history of grade 4 immune related adverse event (irAE) with prior intracavernosal injection (ICI) therapy or failure to recover (\< grade 1) from immune-related adverse event(s) from prior ICI therapy
• •Any of the following therapies prior to registration:
• •* Chemotherapy =\< 28 days
• •* Immunotherapy =\< 28 days
• •* Targeted therapies (e.g., dabrafenib) =\< 21 days
• •* Other investigational agents =\< 28 days
• •* Radiation therapy =\< 14 days
• •* Minor surgical or interventional procedure =\< 7 days
• •* Major surgical procedure =\< 21 days