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A Study of Tilsotolimod in Combo With Ipilimumab vs Ipilimumab Alone in Subjects With Anti-PD-1 Refractory Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03445533
Recruitment Status : Terminated (Lack of Efficacy)
First Posted : February 26, 2018
Results First Posted : November 8, 2022
Last Update Posted : November 8, 2022
Bristol-Myers Squibb
Information provided by (Responsible Party):
Idera Pharmaceuticals, Inc.

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

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Drug: Ipilimumab Drug: Tilsotolimod with Ipilimumab Phase 3

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 anti-PD-1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 481 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : May 30, 2018
Actual Primary Completion Date : June 1, 2021
Actual Study Completion Date : June 1, 2021

Arm Intervention/treatment
Experimental: Arm A: ipilimumab
ipilimumab 3 mg/kg intravenous
Drug: Ipilimumab
Arm A: 4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 1, 4, 7, and 10.
Other Name: Yervoy®

Experimental: Arm B: IMO-2125 plus ipilimumab
IMO-2125 by intratumoral injection plus ipilimumab 3 mg/kg intravenous
Drug: Tilsotolimod with Ipilimumab
IMO-2125 intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 16, 20, and 24. WITH (Arm B): Ipilimumab administered as 4 doses on Weeks 2, 5, 8, and 11. in combination with tilsotolimod
Other Name: IMO-2125 with Yervoy

Primary Outcome Measures :
  1. Summary of Independent Reviewer-Assessed Objective Response Rate (ORR) by RECIST v1.1 [ Time Frame: Response is measured from the date of randomization, until disease progression, death, or start of new anti-cancer therapy (up to 36 months). ]

    The ORR for evaluable participants was calculated using the participant's best overall response (BOR).

    Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for target lesions as assessed by MRI, CT or X-ray: Complete Response (CR) - disappearance of all target lesions; Partial Response (PR) - >=30% decrease from baseline of the sum of diameters of all target lesions; Stable Disease (SD) - does not qualify for CR, PR or Progression; Progressive Disease (PD) - 20% increase in the sum of diameters of target lesions.

    The calculation is derived from measuring the diameter (mm) of the target lesion at baseline and comparing target lesion diameter (mm) at intervals during treatment and/or post-treatment. Based on the percent of tumor decrease or increase, the appropriate category is assigned.

  2. Summary of Overall Survival [ Time Frame: OS is measured from the date of randomization to the date of death from any cause (up to 36 months). ]
    Efficacy measured by overall survival (OS) was defined as the number of participants alive compared to the number of participants that died by treatment group.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03445533

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Sponsors and Collaborators
Idera Pharmaceuticals, Inc.
Bristol-Myers Squibb
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Study Director: Idera Medical Director Idera Pharmaceuticals, Inc.
  Study Documents (Full-Text)

Documents provided by Idera Pharmaceuticals, Inc.:
Study Protocol  [PDF] June 4, 2020
Statistical Analysis Plan  [PDF] February 25, 2021

Additional Information:
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Responsible Party: Idera Pharmaceuticals, Inc. Identifier: NCT03445533    
Other Study ID Numbers: 2125-MEL-301
First Posted: February 26, 2018    Key Record Dates
Results First Posted: November 8, 2022
Last Update Posted: November 8, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Idera Pharmaceuticals, Inc.:
illuminate 301
TLR9 agonist
advanced melanoma
skin cancer
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action