As reported in the Journal of Clinical Oncology by Adi Diab, MD, and colleagues, the phase III ILLUMINATE trial showed adding the Toll-like receptor-9 agonist tilsotolimod to ipilimumab in patients with advanced refractory melanoma produced no benefit.
Adi Diab, MD
Study Details
Four hundred and eighty-one patients with unresectable stage III to IV melanoma progressing during or after anti–PD-1 therapy were enrolled into the international open-label study. They were randomly assigned between May 2018 and March 2020 to receive 24 weeks of tilsotolimod plus ipilimumab (n = 238) or 10 weeks of ipilimumab alone (n = 243). Nine intratumoral injections of tilsotolimod were administered to a single designated lesion over 24 weeks. Ipilimumab at 3 mg/kg was given every 3 weeks from week 2 in the tilsotolimod group and from week 1 in the ipilimumab alone group.
The primary endpoints of the trial were objective response rate on independent central review and overall survival.
Key Findings
Objective response rates were 8.8% (95% confidence interval [CI] = 5.2%–12.4%) in the tilsotolimod/ipilimumab group vs 8.6% (95% CI = 5.1%–12.2%) in the control group; disease control rates were 34.5% vs 27.2%. Median duration of follow-up for overall survival was approximately 23 months. Median overall survival was 11.6 months (95% CI = 9.6–13.5 months) in the tilsotolimod/ipilimumab group vs 10 months (95% CI = 8.1–11.5 months) in the ipilimumab alone group (hazard ratio [HR] = 0.96, 95% CI = 0.77–1.19, P = .7). Median progression-free survival on independent central review was 2.9 months (95% CI = 2.8–3.3) months vs 2.7 months (95% CI = 2.6–2.8 months).
Grade ≥ 3 adverse events occurred in 61.1% of patients in the tilsotolimod/ipilimumab group and 55.5% of the ipilimumab alone group; the most common were anemia (6.4%) and immune-mediated hepatitis (4.3%) in the combination group and anemia (6.4%) and colitis (5.1%) in the monotherapy group. In the tilsotolimod/ipilimumab group, treatment-related adverse events led to discontinuation of tilsotolimod in 15% of patients and ipilimumab in 24.8%; in the ipilimumab alone group, treatment-related adverse events led to discontinuation of the agent in 23.7%.
The investigators concluded, “Combining [intratumoral] tilsotolimod with ipilimumab did not significantly improve the [objective response rate or overall survival] compared with ipilimumab alone in patients with anti–PD-1 advanced refractory melanoma.”
Dr. Diab, of The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Idera Pharmaceuticals, Inc. For full disclosures of the study authors, visit ascopubs.org.
