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

NCT ID: NCT02644967

Last Updated: 2022-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2021-05-31

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.

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.

Conditions

Metastatic Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 2, 8 mg Tilso/Ipi

IMO-2125 intratumoral injection plus ipilimumab

Group Type: EXPERIMENTAL

IMO-2125

Intervention Type: DRUG

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

Ipilimumab

Intervention Type: DRUG

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

Interventions

IMO-2125

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

Intervention Type: DRUG

Ipilimumab

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

Intervention Type: DRUG

Other Intervention Names

tilsotolimod (tilso); Yervoy®

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Idera Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Idera Medical Director

Role: STUDY_DIRECTOR

Idera Pharmaceuticals, Inc.

Locations

The University of Arizona Cancer Center

Tucson, Arizona, United States

Moffitt Cancer Center Research Institute

Tampa, Florida, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Kansas Cancer Center

Westwood, Kansas, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Icahn School Of Medicine at Mount Sinai

New York, New York, United States

Gabrail Cancer Center

Canton, Ohio, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

University of Utah- Huntsman Cancer Institute

Salt Lake City, Utah, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ILLUMINATE-204

Identifier Type: OTHER

Identifier Source: secondary_id

2125-204

Identifier Type: -

Identifier Source: org_study_id