ILLUMINATE 301 Will Study Experimental Immunotherapy for Patients With Advanced Melanoma

June 4, 2019

Investigators are now enrolling for a phase III trial testing the experimental immunotherapy tilsotolimod plus ipilimumab in patients with advanced melanoma who have progressed on anti–PD-1 therapy.

CHICAGO-A group of investigators are now enrolling for a phase III trial, ILLUMINATE 301, comparing an experimental synthetic oligonucleotide called tilsotolimod (IMO-2125) in combination with ipilimumab vs ipilimumab monotherapy in patients with advanced melanoma who have progressed on or after anti–PD-1 therapy. The study rationale and design (abstract TPS9599) was presented during a poster session at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31–June 4 in Chicago.

“IMO-2125 is a TLR [Toll-like receptor] agonist that activates the immune system and results in production of interferon-alpha, better T-cell priming, and increased tumor antigen and human leukocyte antigen expression,” said lead study author Marcus Butler, MD, of Princess Margaret Cancer Center at the University of Toronto.

Tilsotolimod in combination with ipilimumab appears to be well tolerated and is yielding durable response in an ongoing phase I/II clinical trial in patients with advanced melanoma who progressed on or after anti–PD-1 therapy.

“Because no therapy has been shown to prolong survival after failure of first-line anti–PD-1 therapy, this phase III study is designed to show the superiority of tilsotolimod plus ipilimumab over ipilimumab alone,” wrote the study authors.

ILLUMINATE 301 is an international, multicenter, open-label, randomized phase III study of intratumoral tilsotolimod (8 mg) in combination with ipilimumab (3 mg/kg) vs ipilimumab monotherapy in the same patient population. Patients are currently enrolling at 104 centers in 11 countries: the United States, Czech Republic, France, Germany, Italy, the Netherlands, Spain, Sweden, the United Kingdom, Australia, and Canada. The study is planned to include approximately 308 adult patients.

Eligibility requirements include age ≥ 18 years, histologically confirmed unresectable stage III/IV melanoma, at least one measurable lesion that is accessible for injection, an ECOG performance score ≤ 1, and adequate organ function. The exclusion criteria include prior TLR agonists, prior ipilimumab therapy (except as adjuvant therapy completed at least 6 months prior to enrollment), ocular melanoma, and central nervous system disease (except for stable brain metastases).

Patients are being randomized 1:1 and stratified by the duration of their prior anti–PD-1 therapy (≥ 12 weeks vs < 12 weeks), melanoma stage (M1c vs other), and BRAF status and prior targeted therapy (BRAF wild-type vs BRAF mutation positive with targeted therapy vs BRAF mutation positive with no targeted therapy). Disease assessments will be conducted at baseline and week 12, every 8 weeks during the first year, and then every 12 weeks.

Overall response rate by independent central review (RECIST version 1.1) and overall survival are the primary endpoints. The key secondary endpoints are durable response rate, time to response, progression-free survival, patient-reported outcomes, and safety.