A Study of IMO-2125 in Combination With Ipilimumab Versus Ipilimumab Alone in Subjects With Anti-PD-1 Refractory Melanoma (ILLUMINATE-301)


About this study

The purpose of this study is to compare ipilimumab with and without IMO-2125 in advanced melanoma patients.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Subjects must be willing and able to sign the informed consent and comply with the study
  • protocol.
  • Must be ≥18 years of age.
  • 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.
  • Confirmed progression during or after treatment with a PD-1 inhibitor (cannot be part of 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 progression is accompanied by correlative symptoms.
  • In addition, all the following must hold:
    • 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);
    • 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;
    • Subjects who had adjuvant anti-PD-1 treatment are eligible if they have either disease recurrence after the end of adjuvant treatment or on-treatment disease recurrence after ≥ 12 weeks of adjuvant treatment;
    • If subject BRAF mutation status is unknown, before randomization the subject must have BRAF testing performed using an approved assay method;
    • Patients with BRAF-positive tumor(s) are eligible for the study if they received prior treatment with a BRAF inhibitor (alone or in combination with a MEK inhibitor) or declined targeted therapy.
  • ECOG Performance Status ≤ 1.
  • Adequate baseline organ function as defined by:
    • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (1500/mm^3);
    • Platelet count ≥75 x 10^9/L (75,000/mm^3);
    • 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 (≤ Grade 1);
    • Aspartate aminotransferase (AST) ≤ 2.5 x ULN; alanine aminotransferase (ALT) ≤ 2.5 x ULN; AST/ALT < 5 x ULN if liver involvement (≤ Grade 1);
    • Serum bilirubin ≤ 1.5 x ULN, except in subjects with Gilbert’s Syndrome who must have a total bilirubin < 3 mg/dL (≤ Grade 1).
  • Women of childbearing potential (WOCBP) and men must agree to use effective contraceptive methods from screening until at least 90 days after the last dose of either ipilimumab or IMO-2125, whichever is later.
  • Non-childbearing potential is defined as a woman who meets either of the following criteria:
    • postmenopausal state defined as no menses for 12 months without an alternative medical cause, or b) documented hysterectomy, bilateral tubal ligation; or
    • bilateral oophorectomy.
  • Effective contraception methods are defined as one of the following:
    • True abstinence, defined as refraining from heterosexual intercourse, when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception;
    • Condoms and spermicide;
    • Diaphragm and spermicide;
    • Oral or implanted hormonal contraceptive (e.g., Implanon™);
      • NOTE: For subjects in Sweden, low dose oral contraceptives are not permitted.
    • An intra-uterine device.
  • WOCBP must have a negative pregnancy test (serum or urine) according to the Schedule of Evaluations.

Exclusion Criteria:

  • Ocular melanoma.
  • Prior therapy with a TLR agonist, excluding topical agents.
  • Prior ipilimumab with the exception of adjuvant treatment completed ≥ 6 months prior to enrollment.
  • Systemic treatment with IFN-α within the previous 6 months.
  • Known hypersensitivity to any oligodeoxynucleotide.
  • Active autoimmune disease requiring disease-modifying therapy at the time of screening.
  • Subjects with a requirement for systemic steroids receiving >10 mg/day of prednisone (or equivalent) for the 2 weeks preceding start of study treatment.
  • 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).
  • Active systemic infections requiring antibiotics.
  • Known active, hepatitis A, B, or C infection.
  • Known diagnosis of human immunodeficiency virus (HIV) infection.
  • Women who are pregnant or breast-feeding.
  • Prior anaphylactic or other severe infusion reaction associated with human antibody administration that cannot be managed with standard supportive measures.
  • 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.
  • Impaired cardiac function or clinically significant cardiac disease.


Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Mahesh Seetharam, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information


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