A Phase 2 Study to Assess the Safety and Efficacy of IMO-2125 With 8 mg Ipilimumab in Patients With Metastatic Melanoma

Inclusion Criteria

• Patients must have histologically confirmed metastatic melanoma with measurable, stage III (lymph node or in transit lesions) or stage IVA, IVB, or IVC disease.
• Patients must have symptomatic or radiographic progression during or after treatment with a PD-(L)1 inhibitor administered either as monotherapy or in combination.
• The interval between last PD-(L)1 directed treatment and start of study treatment should be at least 21 days.
• Prior BRAF or MEK inhibitor treatment is not required. However, for patients with known BRAF status:
• Those with BRAF wild type may have had a maximum of two previous systemic regimens for the treatment of melanoma.
• Those with a BRAF mutation may have had a maximum of three previous systemic regimens for the treatment of melanoma.
• Prior ipilimumab is permitted.
• Previous treatment with either a PD-1 inhibitor (for patients enrolling on the IMO-2125 + pembrolizumab combination) or CTLA-4 inhibitor (for patients enrolling on the IMO-2125 + ipilimumab combination if applicable) should not have been accompanied by DLT for which permanent discontinuation is recommended (per USPI).
• Patients with a history of Grade ≥2 gastrointestinal symptoms (e.g., diarrhea, colitis) during prior checkpoint inhibitor treatment should be discussed with the Idera Medical Monitor during the Screening Period before starting study treatment.
• Phase 1 patients must have at least two measurable tumor lesions ≥ 1.0 cm that are accessible to biopsy. Phase 2 patients must have at least one measurable lesion (per RECIST v1.1) which may be the same site that is used for the intratumoral injections.
• Patients must be ≥ 18 years of age.
• Patients must have Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
• Patients must meet the following laboratory criteria:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (1500/mm3)
• Platelet count ≥ 75 x 10^9/L (75,000/mm3)
• Hemoglobin ≥ 8.0 g/dL (4.96 mmol/L)
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/minute
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN; alanine aminotransferase (ALT) ≤ 2.5 x ULN; AST/ALT 3 months.

Exclusion Criteria

• Patients who have received prior therapy with a TLR agonist, excluding topical agents. Patients who have received experimental vaccines or other investigational immune therapies should be discussed with the Medical Monitor to confirm eligibility.
• Patients who have received systemic treatment with IFN-α within the previous 6 months prior to enrolling into this study.
• Patients with known hypersensitivity to any oligodeoxynucleotide.
• Patients with active autoimmune disease requiring disease-modifying therapy.
• Patients requiring concurrent systemic steroid therapy higher than physiologic dose (7.5 mg/day of prednisone).
• Patients with any form of active primary or secondary immunodeficiency.
• Patients with another primary malignancy that has not been in remission for at least 3 years.
• Patients with active systemic infections requiring antibiotics or active hepatitis A, B, or C.
• Patients with a known diagnosis of human immunodeficiency virus (HIV) infection.
• Patients who previously had a severe reaction to treatment with a human antibody.
• Patients with known central nervous system, meningeal, or epidural disease.
• Women who are pregnant or breastfeeding.
• Patients with impaired cardiac function or clinically significant cardiac disease.
• Patients with ocular melanoma.