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

• ClinicalTrials.gov Identifier: NCT02644967
• Recruitment Status: Completed
• First Posted: January 1, 2016
• Results First Posted: August 3, 2022
• Last Update Posted: August 3, 2022
• Sponsor: Idera Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Idera Pharmaceuticals, Inc.

Study Description

Brief Summary:

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.

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

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 53 participants
• Allocation: N/A
• Intervention Model: Single Group 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
• Actual Primary Completion Date: February 2020
• Actual Study Completion Date: May 2021

Arms and Interventions

Arm	Intervention/treatment
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 Name: 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 Name: Yervoy®

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. 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.

2. 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.

3. 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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

The University of Arizona Cancer Center

Tucson, Arizona, United States, 85719

United States, Florida

Moffitt Cancer Center Research Institute

Tampa, Florida, United States, 33612

United States, Iowa

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States, 52242

United States, Kansas

University of Kansas Cancer Center

Westwood, Kansas, United States, 66205

United States, New York

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263

Icahn School Of Medicine at Mount Sinai

New York, New York, United States, 10029

United States, Ohio

Gabrail Cancer Center

Canton, Ohio, United States, 44718

United States, Tennessee

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States, 37232

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States, 77030

United States, Utah

University of Utah- Huntsman Cancer Institute

Salt Lake City, Utah, United States, 84112

Sponsors and Collaborators

Idera Pharmaceuticals, Inc.

Investigators

• Study Director: Idera Medical Director; Idera Pharmaceuticals, Inc.

  Study Documents (Full-Text)

Documents provided by Idera Pharmaceuticals, Inc.:

Study Protocol  [PDF] March 27, 2018

Statistical Analysis Plan  [PDF] March 5, 2020

More Information

Additional Information:

For more information 

• Responsible Party: Idera Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02644967
• Other Study ID Numbers: 2125-204; ILLUMINATE-204 ( Other Identifier: Idera Pharmaceuticals, Inc. )
• First Posted: January 1, 2016
• Results First Posted: August 3, 2022
• Last Update Posted: August 3, 2022
• Last Verified: July 2022

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- 204; IMO-2125; tilsotolimod

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Ipilimumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action