A Phase 2 Study to Assess the Safety and Efficacy of IMO-2125 With 8 mg Ipilimumab in Patients With Metastatic Melanoma

July 8, 2022 updated by: Idera Pharmaceuticals, Inc.

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)

The goal of the Phase 1 study was to find the recommended Phase 2 dose of the study drug IMO-2125 (tilsotolimod) that can be given in combination with ipilimumab (ipi) or pembrolizumab (pembro) to participants with metastatic melanoma and assess the safety, tolerability, pharmacokinetics (PK), and immunogenicity when administered in combination with ipilimumab or pembrolizumab.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The open-label single-arm Phase 2 study was designed to assess the recommended dose for safety, tolerability, pharmacokinetics (PK), immunogenicity, and efficacy of 8 mg IMO-2125 (tilsotolimod) when administered in combination with ipilimumab.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
53

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • The University of Arizona Cancer Center
    • Florida
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center Research Institute
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics
    • Kansas
      • Westwood, Kansas, United States, 66205
        • University of Kansas Cancer Center
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • New York, New York, United States, 10029
        • Icahn School of Medicine at Mount Sinai
    • Ohio
      • Canton, Ohio, United States, 44718
        • Gabrail Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt-Ingram Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • University of Utah- Huntsman Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Phase 2, 8 mg Tilso/Ipi
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.
Other Names:
  • tilsotolimod (tilso)
Drug: Ipilimumab
4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 2, 5, 8, and 11.
Other Names:
  • Yervoy®

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Phase 2: Number of Participants With Objective Response Rate (ORR) Using RECIST v1.1
Time Frame: 33 weeks (29 weeks of treatment, 4 weeks follow up)

The following combined analysis populations were used for outcome measures (efficacy analysis N=53):

  • The Phase 2, 8 mg Tilso/Ipi efficacy evaluable population (N=44)
  • The Phase 1, 8 mg Tilso/Ipi evaluable population (N=9)

The ORR for 49 evaluable (4 non-evaluable) participants who received the recommended Phase 2 dose (RP2D) of 8 mg Tilso/Ipi 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.

Overall Response = CR or PR
33 weeks (29 weeks of treatment, 4 weeks follow up)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Phase 2: Progression-free Survival
Time Frame: 33 weeks (29 weeks of treatment, 4 weeks follow up)

The following combined analysis populations were used for outcome measures (efficacy analysis N=53):

  • The Phase 2, 8 mg Tilso/Ipi efficacy evaluable population N=40 (44 with 4 non-evaluable)
  • The Phase 1, 8 mg Tilso/Ipi evaluable population (N=9)

Progression-free survival was defined as the number of months from the initiation of treatment to confirmed disease progression using RECIST v1.1 or death from any cause.
33 weeks (29 weeks of treatment, 4 weeks follow up)
Phase 2: Overall Survival - 6 Months
Time Frame: 6 months

The following combined analysis populations were used for outcome measures (efficacy analysis N=53):

  • The Phase 2, 8 mg Tilso/Ipi efficacy evaluable population N=44 (40 with 4 non-evaluable)
  • The Phase 1, 8 mg Tilso/Ipi evaluable population (N=9)

Overall survival was defined as the number of months from initiation of treatment to death from any cause.
6 months
Phase 2: Overall Survival - 12 Months
Time Frame: 12 months

The following combined analysis populations were used for outcome measures (efficacy analysis N=53):

  • The Phase 2, 8 mg Tilso/Ipi efficacy evaluable population N=40 (44 with 4 non-evaluable)
  • The Phase 1, 8 mg Tilso/Ipi evaluable population (N=9)

Overall survival was defined as the number of months from initiation of treatment to death from any cause.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Idera Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 23, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 31, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 1, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 3, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 8, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2125-204
  • ILLUMINATE-204 (Other Identifier: Idera Pharmaceuticals, Inc.)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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