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

NCT02644967 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2125-204ILLUMINATE-204
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 10

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.

Conditions

Metastatic Melanoma

Keywords

ILLUMINATE- 204; IMO-2125; tilsotolimod

Outcome Measures

Primary Outcomes (1)

• Phase 2: Number of Participants With Objective Response Rate (ORR) Using RECIST v1.1

  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 Outcomes (3)

• Phase 2: Progression-free Survival

  33 weeks (29 weeks of treatment, 4 weeks follow up)

• Phase 2: Overall Survival - 6 Months

  6 months

• Phase 2: Overall Survival - 12 Months

  12 months

Study Arms (1)

Phase 2, 8 mg Tilso/Ipi

EXPERIMENTAL

IMO-2125 intratumoral injection plus ipilimumab

Drug: IMO-2125; Drug: Ipilimumab

Interventions

IMO-2125 DRUG

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

Also known as: tilsotolimod (tilso)

Phase 2, 8 mg Tilso/Ipi

Ipilimumab DRUG

4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 2, 5, 8, and 11.

Also known as: Yervoy®

Phase 2, 8 mg Tilso/Ipi

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed metastatic melanoma with measurable, stage III (lymph node or in transit lesions) or stage IVA, IVB, or IVC disease.
• Patients must have symptomatic or radiographic progression during or after treatment with a PD-(L)1 inhibitor administered either as monotherapy or in combination.
• The interval between last PD-(L)1 directed treatment and start of study treatment should be at least 21 days.
• 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.
• Prior ipilimumab is permitted.
• 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.
• 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.
• Patients must be ≥ 18 years of age.
• Patients must have Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
• Patients must meet the following laboratory criteria:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (1500/mm3)
• Platelet count ≥ 75 x 10\^9/L (75,000/mm3)

You may not qualify if:

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

Sponsors & Collaborators

• Idera Pharmaceuticals, Inc.: lead

Study Sites (10)

The University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

Moffitt Cancer Center Research Institute

Tampa, Florida, 33612, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Icahn School Of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Utah- Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

tilsotolimod; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The analysis populations, as defined in section 6 of the Statistical Analysis Plan, analyzed participants enrolled in the phase 2 study (N=44) and participants rolled in from the phase 1, 8 mg Tilso/Ipi population (N=9).

Results Point of Contact

• Title: Head of Clinical Operations
• Organization: Idera Pharmaceuticals, Inc

lcolfer@iderapharma.com

484-348-1605

Study Officials

• Idera Medical Director

  Idera Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2015
• First Posted: January 1, 2016
• Study Start: December 1, 2015
• Primary Completion: February 1, 2020
• Study Completion: May 1, 2021
• Last Updated: August 3, 2022
• Results First Posted: August 3, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)