Inclusion Criteria:

          -  Subjects must have histologically proven, malignant melanoma, that is advanced (stage
             IV) or is unresectable and therefore considered surgically incurable

          -  Subject's disease must be measurable by immune-related RECIST criteria using clinical
             assessments or imaging

          -  Subjects must have at least one (1), but preferably two (2), sites of readily
             accessible, superficial disease (i.e., cutaneous, subcutaneous, and/or
             readily-palpable lymphadenopathy) that are amenable to repeated hu14.18-IL2 injections
             and two (2) to four (4) biopsies (designated Lesions A (index lesion) and B). These
             lesions must be at least 1 cm, but no greater than 5 cm, in longest diameter.

               -  If there are two lesions, one will be injected with hu14.18-IL2 and undergo
                  biopsies. The second will not undergo injections with hu14.18-IL2, but will
                  undergo two biopsies and be observed clinically. It is preferable, but not
                  required, that these lesions have not received prior RT.

          -  Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of
             0 or 1

          -  Subjects must have received or declined at least one FDA approved immunotherapy
             treatment demonstrating an impact on survival (i.e: anti-CTLA-4 antibody, anti-PD-1
             antibody, IL2, etc).

          -  Subjects with Central Nervous System (CNS) metastases are eligible if the CNS lesions
             are stable for at least 2 months and if tapered off treatment doses of systemic
             corticosteroids for at least 2 weeks prior to enrollment on the trial. Management with
             maintenance physiologic doses of corticosteroids is acceptable.

          -  Subjects to be entered into Phase IB, IC and ID must be evaluated by a radiation
             oncologist and determined to have a need for palliative RT based on current or
             imminent symptoms at a tumor site that is also injectable. If palliative RT is needed
             to one or more disease sites, a separate site of disease that does not require RT must
             remain to enable assessment of systemic disease response.

          -  Subjects must have adequate bone marrow, liver, and renal function as defined by:

               -  Total White Blood Cell (WBC) > 3,000/mm3 (or total neutrophil count > 1,500/mm3),
                  platelets >100,000/mm3, and hemoglobin > 10 g/dL.

               -  AST/ALT ≤ 3 x the upper limit of normal. Total bilirubin ≤ 1.5 x the upper limit
                  of normal (< 3.0 mg/dL for subjects with Gilbert's Syndrome).

               -  Serum creatinine ≤ 1.5 x the upper limit of normal

          -  Subjects with a history of ischemic cardiac disease must complete a stress
             radionuclide scan with results that show no evidence of myocardial ischemia or heart
             failure, as well as normal pulmonary function

          -  Subjects must be willing and able to provide informed written consent for the study.

          -  Subjects must have no immediate requirements for palliative chemotherapy, or surgery.
             Subjects in Arm 1A must have no immediate requirement for palliative RT.

          -  Subjects must be willing and able to discontinue antihypertensive medications if
             advised to do so for the days of hu14.18-IL2 administration.

          -  Subjects must have a washout period of at least 28 days between any prior systemic
             anti-cancer therapy (including immunotherapies) and the first dose of study drug(s).

        Exclusion Criteria:

          -  Subjects with a diagnosed auto-immune disease (exceptions: subjects with controlled
             diabetes mellitus type I, thyroid disease, vitiligo and alopecia areata not requiring
             treatment with immunosuppressants are eligible)

               -  Subjects with a history of diabetes mellitus requiring systemic therapy within
                  the past 3 months (i.e. either oral hypoglycemic agents or insulin) must have a
                  documented Hemoglobin A1c <8.0% at the time of enrollment.

          -  Subjects with known genetic conditions causing pre-disposition to RT toxicity (i.e:
             Li-Fraumeni, ATM deficiency, active scleroderma, etc).

          -  Subjects who cannot provide independent, legal, informed consent.

          -  Women of childbearing potential will be excluded if they are pregnant, nursing, or not
             willing to use effective contraception, as discussed with the treating physician,
             during the treatment period. A negative pregnancy test (serum or urine) is required
             for women of child bearing potential within 14 days before study registration.

               -  A person of childbearing potential is anyone (regardless of sexual orientation,
                  gender identity, having undergone tubal ligation, or remaining celibate by
                  choice) who was born with a uterus and at least one ovary and meets the following
                  criteria

                    -  Has not undergone a hysterectomy or bilateral oophorectomy; or

                    -  Has not been naturally postmenopausal for at least 12 consecutive months
                       (i.e., has had a menses at any time in the preceding 12 consecutive months).

          -  Subjects with symptoms of ischemic cardiac disease, congestive heart failure, or
             myocardial infarction within the immediate preceding 6 months and/or uncontrolled
             cardiac rhythm disturbance

          -  Subjects with significant psychiatric disabilities or seizure disorders

          -  Subjects with symptomatic pleural effusions or ascites.

          -  Subjects with organ allografts

          -  Subjects who require, or are likely to require, systemic treatment doses of
             corticosteroids, or other immunosuppressive drugs, or have used them within 2 weeks of
             registration (clarification: subjects receiving physiologic maintenance or replacement
             doses of systemic steroids are eligible).

          -  Subjects with significant intercurrent illnesses per physician discretion.

          -  Subjects with active or acute infections or active peptic ulcers, unless these
             conditions are adequately corrected or controlled, in the opinion of the treating
             physician.

          -  Subjects with a second malignancy other than adequately treated non-melanoma skin
             cancer. Subjects will be considered eligible if they have been continuously disease
             free for > 5 years from a second malignancy prior to the time of enrollment.

          -  Subjects with known human immunodeficiency virus (HIV) infection, active or chronic
             hepatitis B or hepatitis C infection, or with clinical evidence of hepatitis.

          -  Subjects with a clinically significant neurologic deficit or objective peripheral
             neuropathy (Grade ≥2).

          -  Subjects with known hypersensitivity to hu14.18-IL2 or human immunoglobulin, or those
             who experienced significant immune-related adverse events requiring treatment with
             steroids or other immunosuppressant therapy during prior treatment with ipilimumab, or
             anti-PD1/PD-L1 checkpoint blockade therapy.