A Study to Assess the Safety and Efficacy of Intratumoral IMO-2125 in Combination With Ipilimumab or Pembrolizumab in Patients With Metastatic Melanoma (ILLUMINATE-204)

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: NCT02644967
Recruitment Status : Recruiting
First Posted : January 1, 2016
Last Update Posted : October 5, 2018
Information provided by (Responsible Party):
Idera Pharmaceuticals, Inc.

Brief Summary:
The goal of this clinical research study is to find the recommended dose of the study drug IMO-2125 that can be given in combination with ipilimumab or in combination with pembrolizumab to patients with metastatic melanoma. Researchers also want to learn if the study drug combination can help to control the disease. The safety of the drug combination will also be studied.

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Drug: IMO-2125 Drug: Ipilimumab Drug: Pembrolizumab Phase 1 Phase 2

Detailed Description:
This is an open-label Phase 1/2 study to determine the recommended dose and assess the safety, tolerability, pharmacokinetics (PK), immunogenicity, and efficacy of IMO-2125 when administered in combination with ipilimumab or pembrolizumab. The study will be conducted in 2 parts; a dose-escalation portion (Phase 1) to evaluate safety and tolerability of multiple dose levels and a Phase 2 portion to assess efficacy.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study to Assess the Safety and Efficacy of Intratumoral IMO-2125 in Combination With Ipilimumab or Pembrolizumab in Patients With Metastatic Melanoma ILLUMINATE-204)
Actual Study Start Date : December 2015
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : May 2020

Arm Intervention/treatment
Experimental: Arm 1
IMO-2125 intratumoral injection plus ipilimumab
Drug: IMO-2125
Drug: IMO-2125 Intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 17, 23, and 29.

Drug: Ipilimumab
4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 2, 5, 8, and 11.
Other Name: Yervoy®

Experimental: Arm 2
IMO-2125 intratumoral injection plus pembrolizumab
Drug: IMO-2125
Drug: IMO-2125 Intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 17, 23, and 29.

Drug: Pembrolizumab
Drug: Pembrolizumab Administered intravenously at a dose of 200 mg over 30 minutes every 3 weeks beginning on Week 2.
Other Name: Keytruda®

Primary Outcome Measures :
  1. Phase 1: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 to determine the recommended Phase 2 dose of IMO-2125. [ Time Frame: 33 weeks (29 weeks of treatment, 4 weeks follow up ]
  2. Phase 2: Number of participants with objective response using RECIST v1.1 [ Time Frame: 33 weeks (29 weeks of treatment, 4 weeks follow up ]

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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. Patients must have histologically confirmed metastatic melanoma with measurable, stage III (lymph node or in transit lesions) or stage IVA, IVB, or IVC disease.
  2. Patients must have symptomatic or radiographic progression during or after treatment with a PD-(L)1 inhibitor administered either as monotherapy or in combination.

    1. The interval between last PD-(L)1 directed treatment and start of study treatment should be at least 21 days.
    2. 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.
    3. Prior ipilimumab is permitted.
    4. 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.
  3. 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.
  4. Patients must be ≥ 18 years of age.
  5. Patients must have Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
  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 patients 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 IMO-2125, 3 months after the last dose of ipilimumab or at least 4 months after the last dose of pembrolizumab.
  8. Patients must have an anticipated life expectancy > 3 months.

Exclusion Criteria:

  1. 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.
  2. Patients who have received systemic treatment with IFN-α within the previous 6 months prior to enrolling into this study.
  3. Patients with known hypersensitivity to any oligodeoxynucleotide.
  4. Patients with active autoimmune disease requiring disease-modifying therapy.
  5. Patients requiring concurrent systemic steroid therapy higher than physiologic dose (7.5 mg/day of prednisone).
  6. Patients with any form of active primary or secondary immunodeficiency.
  7. Patients with another primary malignancy that has not been in remission for at least 3 years.
  8. Patients with active systemic infections requiring antibiotics or active hepatitis A, B, or C.
  9. Patients with a known diagnosis of human immunodeficiency virus (HIV) infection.
  10. Patients who previously had a severe reaction to treatment with a human antibody.
  11. Patients with known central nervous system, meningeal, or epidural disease.
  12. Women who are pregnant or breastfeeding.
  13. Patients with impaired cardiac function or clinically significant cardiac disease.
  14. Patients with ocular melanoma.

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): NCT02644967

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

United States, Arizona
The University of Arizona Cancer Center Recruiting
Tucson, Arizona, United States, 85719
Contact: Ahmed Monadhil Alsafar   
United States, Florida
Moffitt Cancer Center Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Deanryan De'Aquino    813-745-3998   
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Heidi Haugland    319-384-5285   
United States, Kansas
University of Kansas Cancer Center Recruiting
Westwood, Kansas, United States, 66205
Contact: Kaitlyn Gerwick         
Principal Investigator: Gary Doolittle, MD         
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Maria Levis   
Icahn School Of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Nancy Lowe    212-824-7324   
Principal Investigator: Philip Friedlander, MD, PhD         
United States, Ohio
Gabrail Cancer Center Recruiting
Canton, Ohio, United States, 44718
Contact: Nashat Y Gabrail         
Principal Investigator: Nashat Y Gabrail, MD         
United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Carla B Ramsey    615-875-8605   
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Marihella James    713-563-6784   
United States, Utah
University of Utah- Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Carolynn Hunter    801-213-4299   
Principal Investigator: Wallace Akerley, MD         
Sponsors and Collaborators
Idera Pharmaceuticals, Inc.
Study Director: Idera Medical Director Idera Pharmaceuticals, Inc.

Additional Information:
Responsible Party: Idera Pharmaceuticals, Inc. Identifier: NCT02644967     History of Changes
Other Study ID Numbers: 2125-204
First Posted: January 1, 2016    Key Record Dates
Last Update Posted: October 5, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Idera Pharmaceuticals, Inc.:

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
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs