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

NCT03445533

Description:

A Phase 3 comparison of ipilimumab with and without IMO-2125 in advanced melanoma

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of IMO-2125 in Combination With Ipilimumab Versus Ipilimumab Alone in Subjects With Anti-PD-1 Refractory Melanoma (ILLUMINATE-301)
  • Official Title: A Randomized Phase 3 Comparison of IMO-2125 With Ipilimumab Versus Ipilimumab Alone in Subjects With Anti-PD-1 Refractory Melanoma (ILLUMINATE-301)

Clinical Trial IDs

  • ORG STUDY ID: 2125-MEL-301
  • NCT ID: NCT03445533

Conditions

  • Metastatic Melanoma

Interventions

DrugSynonymsArms
IpilimumabYervoy®Arm A: ipilimumab
IMO-2125Arm B: IMO-2125 plus ipilimumab

Purpose

A Phase 3 comparison of ipilimumab with and without IMO-2125 in advanced melanoma

Detailed Description

      A Phase 3 global, multi-center, open-label comparison of ipilimumab with and without
      intratumoral IMO-2125 in subjects with advanced melanoma who had confirmed disease
      progression while on nivolumab or pembrolizumab
    

Trial Arms

NameTypeDescriptionInterventions
Arm A: ipilimumabExperimentalipilimumab 3 mg/kg intravenous
  • Ipilimumab
Arm B: IMO-2125 plus ipilimumabExperimentalIMO-2125 by intratumoral injection plus ipilimumab 3 mg/kg intravenous
  • Ipilimumab
  • IMO-2125

Eligibility Criteria

        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 either
             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 nivolumab or
                  pembrolizumab 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 nivolumab or pembrolizumab 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 should be 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. Known central nervous system, meningeal, or epidural 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.

         15. Impaired cardiac function or clinically significant cardiac disease.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Compare the efficacy of IMO-2125 in combination with ipilimumab versus ipilimumab alone
Time Frame:OS is measured from the date of randomization to the date of death from any cause (up to 48 months).
Safety Issue:
Description:Efficacy measured by overall survival (OS)

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Idera Pharmaceuticals, Inc.

Trial Keywords

  • Melanoma
  • PD1
  • PD-1
  • refractory
  • metastatic
  • IMO-2125
  • illuminate 301
  • TLR9 agonist
  • advanced melanoma
  • CTLA4
  • CTLA-4
  • immunotherapy
  • skin cancer
  • ILLUMINATE-301

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