Please select the eligibility criteria that correspond to the clinical trial below.
Title: Adjuvant Nivolumab or Ipilimumab + Nivolumab Determined By Pathological Response To A Single Dose Of Neoadjvuant Nivolumab
Brief Summary: Subjects with resectable melanoma will receive neoadjuvant nivolumab followed by surgical resection. Post-operatively, subjects will receive open-label treatment with up to 1 year of adjuvant nivolumab or ipilimumab plus nivolumab as determined by pathologic response at the time of resection.


Options:
A: Inclusion Criteria:

* Adults at least 18 years of age.
* World Health Organization (WHO) Performance Status 0 or 1.
* Cytologically or histologically confirmed resectable stage III cutaneous melanoma (unknown primary also allowed) with one or more macroscopic lymph node metastases (measurable according to RECIST 1.1), that can be biopsied, and no history of in-transit metastases within the last 6 months.
* No other malignancies, except adequately treated and a cancer-related life-expectancy of more than 5 years.
* Patient willing to undergo quadruple tumor biopsies and extra blood withdrawal during screening, week 3 and in case of relapse.
* The biopsies at screening should contain at least 30% tumor cells in order to get a reliable IFN-gamma signature
* No immunosuppressive medications within 6 months prior trial registration.
* Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Neutrophils ≥1.5x109/L, Platelets ≥100 x109/L, Hemoglobin ≥5.5 mmol/L, Creatinine ≤1.5x ULN, AST ≤ 1.5 x ULN, ALT ≤ 1.5 x ULN, Bilirubin ≤1.5 X ULN.
* Normal LDH.
* Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of ipilimumab + nivolumab.
* Patient is capable of understanding and complying with the protocol requirements and has signed the Informed Consent document.

Exclusion Criteria:

Distantly metastasized melanoma

* Uveal or mucosal melanoma.
* History of in-transit metastases within the last 6 months.
* No measurable lymph node lesion according to RECIST 1.1.
* Subjects with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy.
* Patients with any active gastrointestinal disorder that could interfere with the absorption of domatinostat (as per judgement of the investigator), such as ulcerative colitis, Crohn's disease, diabetic gastroparesis, or other syndromes characterized by malabsorption.
* Prior CTLA-4 or PD-1/PD-L1 targeting immunotherapy.
* Prior targeted therapy targeting BRAF and/or MEK.
* Prior radiotherapy.
* Patients will be excluded if they test positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody), indicating acute or chronic infection; if treated and being at least one year free from HCV patients are allowed to participate.
* Patients will be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
* Allergies and Adverse Drug Reaction:

  * History of allergy to study drug components;
  * History of severe hypersensitivity reaction to any monoclonal antibody.
* Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events.
* Patients with a marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval \>450 msec (Grade 1 NCI-CTCAE); Long-QT-Syndrome) and patients receiving agents known to prolong the QT interval and known risk of Torsades de Pointes.
* Patients with significant current cardiovascular disease including:

  * Unstable angina pectoris within 6 months prior to screening
  * Uncontrolled hypertension
  * Congestive heart failure (New York Heart Association (NYHA) Class III or IV) related to primary cardiac disease
  * Conditions requiring anti-arrhythmic therapy (patients with status post pace maker implantation can be included)
  * Symptomatic ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the trial entry
* Women who are pregnant or lactating
* Use of other investigational drugs before study drug administration 30 days and 5 half-times before trial registration.
B: Inclusion Criteria:

* Any patient with measurable metastatic (stage IV or locally advanced stage III) cutaneous melanoma and an expected survival of greater than three months will be considered
* Serum creatinine of 1.6 mg/dl or less
* Total bilirubin 1.6 mg/dl or less
* White blood cell (WBC) 3000/mm\^3 or greater
* Platelet count 90,000 mm\^3 or greater
* Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less then three times normal
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Patients of both genders must be willing to practice effective birth control during this trial
* Pathologic confirmation of cutaneous melanoma; patients may enter the study with a pathologic diagnosis of cutaneous melanoma from any institution; all slides will be reviewed at National Institutes of Health (NIH) (department of Anatomic Pathology) and if the diagnosis is not confirmed, the patient will be excluded from the study
* Tissue type human leukocyte antigen (HLA) A0201

Exclusion Criteria:

* Patients who have types of melanoma other than cutaneous, i.e. ocular or mucosal
* Patients who are undergoing or have undergone in the past 4 weeks any other form of therapy except surgery for their cancer, including radiation therapy to any site
* Patients who have active systemic infections, coagulation disorders, autoimmune disease or history of other major medical illnesses such as insulin dependent diabetes mellitus, cardiac ischemia, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary diseases and inflammatory bowel disorders
* Patients who have significant psychiatric disease which in the opinion of the principal investigator would prevent adequate informed consent or render immunotherapy unsafe or contraindicated
* Patients who require steroid therapy or steroid-containing compounds, or have used systemic steroids in the past 4 weeks, or have used topical or inhalational steroids in the past 2 weeks
* Patients who are pregnant
* Patients who are known to be positive for viral hepatitis B or C (hepatitis B surface antigen \[HBsAg\] or anti hepatitis C virus \[HCV\]) or human immunodeficiency virus (HIV) (HIV antibody)
* Patients who have any form of primary or secondary immunodeficiency
* Patients who have received previous high dose IL-2 (\> 600,000 IU/kg)
* Patients who have received previous gp100 vaccines
* Patients who have an abnormal stress cardiac test (stress thallium, stress multi gated acquisition scan \[MUGA\], dobutamine echocardiogram or other stress test that will rule out cardiac ischemia)
* Patients who have abnormal pulmonary function tests (forced expiratory volume in one second \[FEV1\] \< 65% or forced vital capacity \[FVC\] \< 65% of predicted)
* Patients who have brain metastasis or history of brain metastasis
* No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for 5 years
C: Inclusion Criteria:

* Histological or cytological confirmed melanoma that is metastatic or unresectable; patients must have a history of cutaneous, mucosal or unknown primary site
* Patients who have received prior systemic cytotoxic chemotherapy for treatment of melanoma are ineligible; the following groups are eligible with regard to prior systemic therapy either in the adjuvant or metastatic disease setting:

  * No prior therapy
  * Immunotherapy consisting of interferon, interleukin-2, granulocyte macrophage colony-stimulating factor (GM-CSF) or vaccine
  * One prior investigational therapy (cannot be chemotherapy or an inhibitor of rat sarcoma \[Ras\], serine/threonine kinase \[Raf\], or mitogen-activated protein kinase kinase \[MEK\])

    * NOTE: Chemotherapy given via isolated limb perfusion is allowed
* Prior radiation therapy is allowed; however, if radiation has been administered to a lesion, there must be radiographic evidence of progression of that lesion in order for that lesion to constitute measurable disease or to be included in the measured target lesions
* All sites of disease must be evaluated within 4 weeks of registration; patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* White blood count \>= 3,000/mm\^3
* Absolute granulocyte count \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Serum creatinine =\< 2.0 x upper limit of normal (ULN) or serum creatinine clearance (CrCl) \>= 40 ml/min (neither drug is cleared by the kidney)
* Total bilirubin =\< 1.5 x ULN (\< 3.0 x ULN in the presence of Gilbert's disease)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x ULN (=\< 5.0 ULN in the presence of liver metastases)
* International normalized ratio (INR) =\< 1.5 and a partial thromboplastin time (PTT) within normal limits (patients who are on therapeutic anticoagulation with warfarin should have documentation of a normal prothrombin time \[PT\]/PTT prior to initiating that therapy)
* Patients must not have ocular melanoma
* Patients must have discontinued immunotherapy or radiation therapy at least 4 weeks prior to initiation of treatment and recovered from adverse events due to those agents
* Patients must not receive any other investigational agents during the period on study or the four weeks prior to initiation of treatment
* Patients must not have a history or clinical evidence of brain metastasis; patients must be evaluated with a head magnetic resonance imaging (MRI) within 4 weeks prior to enrollment
* Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast; patients with other malignancies are eligible if they have been continuously disease-free for \>= 5 years prior to the time of randomization
* Patients must not have any evidence of bleeding diathesis
* Patients must not have a serious intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, clinically significant cardiovascular disease (e.g. uncontrolled hypertension, myocardial infarction, unstable angina), New York Heart Association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or grade II or greater peripheral vascular disease within 1 year prior to study entry, or psychiatric illness/social situations that would limit compliance with study requirements
* Patients must not be taking cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or phenobarbital), rifampin or St. John's Wort
* Women must not be pregnant or breast-feeding
* All females of childbearing potential must have a blood test or urine study within 4 weeks prior to registration to rule out pregnancy
* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately as well
* Human immunodeficiency virus (HIV)-positive patients are excluded from the study
D: Inclusion Criteria:

* The subject must have clinical stage III resectable melanoma per investigator. Subjects may not have a diagnosis of uveal or mucosal melanoma.
* Either the subject or the subject's legally authorized representative must be willing and able to provide written informed consent before the performance of any protocol-related procedures.
* The subject must be ≥18 years of age on day of signing informed consent.
* The subject must have a performance status of 0 or 1 on the ECOG Performance Scale.
* The subject must demonstrate adequate organ function as defined in Table 1; all screening labs must be performed within 28 days of treatment initiation.

  * Hematologic System: Absolute neutrophil count (ANC) ≥1500/mcL; Platelets ≥100,000/mcL; Hemoglobin ≥9 g/dL or ≥5.6 mmol/L
  * Renal System: Serum creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥50 mL/min for subject with creatinine levels \>1.5 X institutional ULN
  * Hepatic System: Serum total bilirubin ≤1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \>1.5 ULN; AST (SGOT) and ALT (SPGT) ≤2.5 X ULN OR ≤5 X ULN for subjects with liver metastases
* A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies: A.) Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR B.) A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and is willing to use a highly effective method of contraception or abstain from heterosexual intercourse for at least 2 weeks prior to the time of first dose of study medication through 5 months after the last dose of study medication.
* Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
* Male subjects must agree to follow the contraceptive guidance in Appendix 3 starting with the first dose of study medication, while on study, through 7 months after the last dose of study medication.

Exclusion Criteria:

* Subject has unresectable disease; i.e. in the opinion of the surgical oncologist, all of the subject's melanoma cannot be completely removed with a clear margin.
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), interferon, high dose IL-2 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
* Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to the first dose of study drug. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy are an exception to this criterion.
* If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
* Subject has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including G-CSF, GM-CSF or recombinant erythropoietin) within 4 weeks to the first dose of study drug.
* Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
* Has a known additional malignancy that is progressing or requires active treatment. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
* Has active autoimmune disease that has required systemic treatment in the past 3 months (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
* Has evidence of active interstitial lung disease or a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
* Has an active infection requiring systemic therapy.
* Patients known to be positive for Human Immunodeficiency Virus (HIV) if they have a CD4 count of less than 350 mm3 and a serum HIV viral load \> 25,000 IU/mL
* Has active Hepatitis B infection or active Hepatitis C virus infection as determined by medical record review.
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 5 months, if female, or 7 months, if male, after the last dose of investigational drug.
* Prisoners or subjects who are involuntarily incarcerated.
* Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

Answer: D