A Study of Intratumoral IMO-2125 in Patients With Refractory Solid Tumors (ILLUMINATE-101)

• ClinicalTrials.gov Identifier: NCT03052205
• Recruitment Status: Active, not recruiting
• First Posted: February 14, 2017
• Last Update Posted: August 8, 2019
• Sponsor: Idera Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Idera Pharmaceuticals, Inc.

Study Description

Brief Summary:

This is a Phase 1b study that incorporates dose expansion cohorts to further evaluate promising clinical or biological activity.

Condition or disease	Intervention/treatment	Phase
Refractory Solid Tumors; Melanoma	Drug: IMO-2125	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 54 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b Study of Intratumoral IMO-2125 in Patients With Refractory Solid Tumors (ILLUMINATE-101)
• Actual Study Start Date: June 9, 2017
• Actual Primary Completion Date: July 31, 2019
• Estimated Study Completion Date: April 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: IMO-2125 at escalating dose levels; IMO-2125 at escalating dose levels by intratumoral injection	Drug: IMO-2125; IMO-2125 will be administered by intratumoral injection on Days 1, 8, and 15 of Cycle 1 and on Day 1 of each subsequent cycle.

Outcome Measures

Primary Outcome Measures :

1. Dose Evaluation Cohorts, non-Melanoma Dose Evaluation Cohorts: Number of patients with treatment-related adverse events as assessed by CTCAE to determine the recommended Phase 2 dose (RP2D). [ Time Frame: 51 weeks of treatment ]
2. Dose Evaluation Cohorts, non-Melanoma Dose Evaluation Cohorts: Objective response rate [ Time Frame: Assessed every 6 weeks for duration of study participation, which is estimated to be 51 weeks ]
3. Melanoma Expansion Cohort: Objective response rate [ Time Frame: Assessed every 9 weeks for duration of study participation, which is estimated to be 51 weeks ]
4. Melanoma Expansion Cohort: Number of patients with treatment-related adverse events as assessed by CTCAE [ Time Frame: 51 weeks of treatment ]

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 or cytologically confirmed diagnosis of cancer not amenable to curative therapy.

2. Patients who have a diagnosis for which a PD-(L)-1 inhibitor has been approved must have previously received treatment with one of these therapies.

   a. Melanoma Dose Expansion: Patients must have histologically confirmed metastatic melanoma (ocular melanoma not included) which has progressed on or after treatment with a PD-(L)1 inhibitor.

3. a) Dose Evaluation Portion: Patients should have at least one lesion accessible for intratumoral injection and biopsy.

   b) Melanoma Expansion Cohort: Patients must have at least one target lesion by Response Evaluation Criteria for Solid Tumors (RECIST v1.1), with at least one lesion accessible for intratumoral injection. Tumor biopsies are not required in the expansion cohort.

4. Patients must be 18 years of age or older.
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 109/L (≥1500/mm3)
   2. Platelet count ≥75 x 109/L (≥75,000/mm3)
   3. Hemoglobin ≥8.0 g/dL (≥4.96 mmol/L)
   4. Serum creatinine ≤1.5 x ULN or calculated 24-hour creatinine clearance ≥60 mL/minute
   5. Aspartate aminotransferase (AST) ≤2.5 x ULN; ALT ≤2.5 x ULN or AST/ALT <5 x ULN if liver involvement
   6. Total bilirubin ≤1.5 x ULN, except in patients with Gilbert's Syndrome who must have a total bilirubin <3 mg/dL (51.3 μmol/L)
7. Women of childbearing potential and men must agree to use effective contraceptive methods from Screening throughout the study treatment period and until at least 4 weeks after the last dose of study drug.
8. Patients must be willing and able to provide signed informed consent and comply with the study protocol.

Exclusion Criteria:

1. Patients who have received prior therapy with a TLR agonist Patients who have received experimental vaccines or immune therapies other than PD-(L)1 or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors (e.g., Imlygic®) should be discussed with the Medical Monitor to confirm eligibility.

   Note: (prior treatment with a topical TLR agonist (e.g. imiquimod) is permitted).

2. Patients who have received treatment with IFN-α within the previous 6 months prior to enrollment.
3. Patients with known hypersensitivity to any oligodeoxynucleotide that cannot be adequately managed with appropriate prophylaxis; e.g. steroids.
4. Patients with active autoimmune disease requiring disease-modifying therapy.
5. Patients requiring concurrent systemic steroid therapy higher than physiologic dosage (>10mg/day of prednisone or equivalent).
6. Patients with another primary malignancy that has not been in remission for at least 3 years, unless approved by the Idera Medical Monitor. The following are exempt from the 3-year limit: non-melanoma skin cancer, curatively treated localized prostate cancer with non-detectable prostate-specific antigen, cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Papanicolaou (Pap) smear, and thyroid cancer (except anaplastic).
7. Patients with active infections requiring systemic treatment.
8. Patients who are known to be hepatitis B surface antigen positive.
9. Patients with a known diagnosis of human immunodeficiency virus (HIV) infection.
10. Women who are pregnant or breastfeeding.
11. Patients with known central nervous system, meningeal, or epidural disease. Patients with stable brain metastases following definitive local treatment are eligible if steroid requirement is <10 mg/day of prednisone (or equivalent).

12. Patients with impaired cardiac function or clinically significant cardiac disease:

    1. New York Heart Association Class III or IV cardiac disease, including preexisting clinically significant ventricular arrhythmia, congestive heart failure, or cardiomyopathy
    2. Unstable angina pectoris ≤6 months prior to study participation
    3. Acute myocardial infarction ≤6 months prior to study participation
    4. Other clinically significant heart disease (i.e., Grade ≥3 hypertension, history of labile hypertension, or poor compliance with an anti-hypertensive regimen)
13. Have not recovered (to baseline or Grade ≤1) from toxicity associated with prior treatment.

Contacts and Locations

Locations

United States, Arizona

Scottsdale Healthcare Hospitals DBA Honor Health

Scottsdale, Arizona, United States, 85258

The University of Arizona Cancer Center

Tucson, Arizona, United States, 85724

United States, California

University of California San Francisco (UCSF)

San Francisco, California, United States, 94143

United States, New York

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263

United States, Ohio

The Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

United States, Pennsylvania

St. Luke's Hospital

Easton, Pennsylvania, United States, 18045

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States, 15232

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States, 77030

Israel

Rambam Medical Center

Haifa, Israel, 3109601

Hadassah Medical Center

Jerusalem, Israel, 9112001

Rabin Medical Center Beilinson Campus

Petah tikva, Israel, 49100

The Ella Lemelbaum Institute for Immuno-Oncology

Ramat Gan, Israel, 5265601

Sponsors and Collaborators

Idera Pharmaceuticals, Inc.

Investigators

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

More Information

• Responsible Party: Idera Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03052205
• Other Study ID Numbers: 2125-RST-101
• First Posted: February 14, 2017
• Last Update Posted: August 8, 2019
• Last Verified: August 2019

• 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-101; melanoma

Additional relevant MeSH terms:

Melanoma; Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas