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.