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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03445533
Recruitment Status : Recruiting
First Posted : February 26, 2018
Last Update Posted : July 6, 2018
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: IMO-2125 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 nivolumab or pembrolizumab

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 308 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 : February 28, 2018
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

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

Drug: IMO-2125
IMO-2125 intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 16, 20, and 24.

Primary Outcome Measures :
  1. 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). ]
    Efficacy measured by overall survival (OS)

  2. Compare the efficacy of IMO-2125 in combination with ipilimumab versus ipilimumab alone [ 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). ]
    Efficacy measure by overall response rate (ORR)

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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 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.

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

Contact: Idera Study Monitor 877-888-6550 ext 2

United States, Alabama
University of Alabama at Birmingham (UAB) Recruiting
Birmingham, Alabama, United States, 35294
Contact: Robert Conry, MD         
United States, Arizona
Banner MD Anderson Cancer Center Recruiting
Gilbert, Arizona, United States, 85234
Contact: Tomislav Dragovich, MD         
United States, California
University of Southern California Recruiting
Los Angeles, California, United States, 90033
Contact: S Jhimlee    323-865-3071   
Contact: Kristina Massopust    949-474-5733   
Principal Investigator: Gino In, MD         
University of California, Los Angeles (UCLA) Recruiting
Los Angeles, California, United States, 90095
Contact: Bartosz Chmielowski, MD, PhD         
Sutter Health Sacramento Recruiting
Sacramento, California, United States, 95816
Contact: Deepti Behl, MD         
University of California, San Diego (UCSD) - Moores Cancer Center Recruiting
San Diego, California, United States, 92093
Contact: Mina Nikanjam, MD         
Stanford Cancer Center Recruiting
Stanford, California, United States, 94305
Contact: Sunil Reddy, MD         
United States, Florida
Mount Sinai Medical Center of Florida, Inc. Recruiting
Miami Beach, Florida, United States, 33140
Contact: Jose Lutsky, MD         
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Pamela Sroka    312-942-5526      
Contact: Patricia Nelson    312-942-8004   
Principal Investigator: Timothy Kuzel, MD         
United States, Indiana
Community Health Network Recruiting
Indianapolis, Indiana, United States, 46256
Contact: Natraj Ammakkanavar, MD         
United States, Kentucky
Norton Cancer Institute Recruiting
Louisville, Kentucky, United States, 40202
Contact: Jae Jung, MD         
United States, Maryland
Greater Baltimore Medical Center (GBMC) Recruiting
Baltimore, Maryland, United States, 21204
Contact: Mei Tang, MD         
United States, New Jersey
The Valley Hospital Recruiting
Ridgewood, New Jersey, United States, 07450
Contact: Jin Lee, MD         
United States, Ohio
The Christ Hospital Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Philip Leming, MD         
United States, Pennsylvania
St. Luke's Hospital - Anderson Campus Recruiting
Easton, Pennsylvania, United States, 18045
Contact: Robyn Rex    484-503-4152   
Contact: Carolyn Seith    484-503-4153   
Principal Investigator: Sangiv Agarwala, MD         
Australia, Queensland
Greenslopes Private Hospital Recruiting
Greenslopes, Queensland, Australia, 4120
Contact: Victoria Atkinson         
Icon Cancer Center Recruiting
South Brisbane, Queensland, Australia, 4101
Contact: Andrea Tazbirkova, MD   
Gold Coast University Hospital Recruiting
Southport, Queensland, Australia, 4215
Contact: Marcin Dzienis, MD   
Australia, South Australia
Queen Elizabeth Hospital Recruiting
Woodville South, South Australia, Australia, 5011
Contact: Rachel Roberts-Thompson, MD         
Australia, Victoria
Box Hill Hospital Recruiting
Box Hill, Victoria, Australia, 3128
Contact: Phillip Parente, MD         
University Hospital Geelong Recruiting
Geelong, Victoria, Australia, 3220
Contact: Anna Lomax, MD         
Sponsors and Collaborators
Idera Pharmaceuticals, Inc.
Study Director: Idera Medical Director Idera Pharmaceuticals, Inc.

Additional Information:
Responsible Party: Idera Pharmaceuticals, Inc. Identifier: NCT03445533     History of Changes
Other Study ID Numbers: 2125-MEL-301
First Posted: February 26, 2018    Key Record Dates
Last Update Posted: July 6, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs