Inclusion Criteria:

          1. Subjects must be willing and able to sign the informed consent and comply with the
             study protocol.

          2. Subjects must be ≥18 years of age.

          3. Subjects must have histologically confirmed metastatic melanoma with measurable (by
             RECIST v1.1), stage III (lymph node or in transit lesions) or stage IVA, IVB, or IVC
             disease that is accessible for injection.

          4. Patients must have confirmed progression during or after treatment with a PD-1
             inhibitor (cannot be part of a bi-specific antibody) e.g. nivolumab or pembrolizumab.
             Confirmed progression is defined as:

               -  Radiological progression (confirmed at least 4 weeks after the initial scan
                  showing PD); or

               -  (For progression based solely on worsening of non-target or new, non-measurable
                  disease) confirmation by an additional scan at least 4 weeks after the initial
                  scan unless it is accompanied by correlative symptoms.

             In addition, all the following must hold:

               1. No intervening anti-cancer therapy between the last course of PD-1 inhibitor
                  treatment and the first dose of study treatment is allowed except for local
                  measures (e.g., surgical excision or biopsy, focal radiation therapy).

               2. The interval between last PD-1 inhibitor and start of study treatment should be
                  at least 21 days with no residual anti-PD-1-related immune toxicities in excess
                  of Grade 1 severity.

               3. If BRAF mutation status is unknown, before randomization the subject must have
                  BRAF testing performed using an approved assay method.

               4. Patients with BRAF-positive tumor(s) are eligible for the study if they received
                  prior treatment with a BRAF inhibitor (alone of in combination with a MEK
                  inhibitor) or declined targeted therapy.

          5. Patients must have Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.

          6. Patients must meet the following laboratory criteria:

               1. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (1500/mm3)

               2. Platelet count ≥ 75 x 10^9/L (75,000/mm3)

               3. Hemoglobin ≥ 8.0 g/dL (4.96 mmol/L)

               4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine
                  clearance ≥ 60 mL/minute

               5. Aspartate aminotransferase (AST) ≤ 2.5 x ULN; alanine aminotransferase (ALT) ≤
                  2.5 x ULN; AST/ALT < 5 x ULN if liver involvement

               6. Serum bilirubin ≤ 1.5 x ULN, except in subjects with Gilbert's Syndrome who must
                  have a total bilirubin < 3 mg/dL

          7. Women of childbearing potential (WOCBP) and men must agree to use effective
             contraceptive methods from Screening throughout the study treatment period and until
             at least 90 days after the last dose of either ipilimumab or IMO-2125, whichever is
             later.

          8. WOCBP must have a negative pregnancy test (serum or urine).

        Exclusion Criteria:

          1. Ocular melanoma.

          2. Prior therapy with a toll-like receptor (TLR) agonist, excluding topical agents.

          3. Prior ipilimumab treatment with the exception of adjuvant treatment completed ≥6
             months prior to enrollment

          4. Systemic treatment with interferon (IFN)-α within the previous 6 months.

          5. Known hypersensitivity to any oligodeoxynucleotide.

          6. Active autoimmune disease requiring disease-modifying therapy at the time of
             Screening.

          7. Subjects requiring systemic steroid therapy receiving >10 mg/day of prednisone (or
             equivalent) for the 2 weeks preceding start of study.

          8. Subjects with another primary malignancy that has not been in remission for at least 3
             years, with the exception of non-melanoma skin cancer, curatively treated localized
             prostate cancer with non-detectable prostate-specific antigen, cervical carcinoma in
             situ on biopsy or a squamous intraepithelial lesion on Papanicolaou (Pap) smear, and
             thyroid cancer (except anaplastic).

          9. Active systemic infections requiring antibiotics

         10. Active hepatitis A, B, or C infection.

         11. Known diagnosis of human immunodeficiency virus (HIV) infection.

         12. Women who are pregnant or breastfeeding.

         13. Prior severe reaction to treatment with a human antibody that cannot be managed with
             standard supportive measures.

         14. Presence of known central nervous system, meningeal, or epidural metastatic disease.
             However, subjects with known brain metastases are allowed if the brain metastases are
             stable for ≥4 weeks before the first dose of study treatment. Stable is defined as
             neurological symptoms not present or resolved to baseline, no radiologic evidence of
             progression, and steroid requirement of prednisone ≤10 mg/day or equivalent

         15. Impaired cardiac function or clinically significant cardiac disease.