Tilsotolimod Plus Ipilimumab Fails to Significantly Improve Outcomes for Patients With Advanced Refractory Melanoma
According to results from the phase 3 ILLUMINATE-301 study, the addition of tilsotolimod to ipilimumab did not significantly improve outcomes compared to ipilimumab alone among patients with unresectable, advanced refractory melanoma.
“Patients [with melanoma] may ultimately progress during or after [immune checkpoint inhibitor] treatment and require subsequent treatment options,” stated Adi Diab, MD, University of Texas MD Anderson Cancer Center, Houston, Texas, and coauthors. “Tilsotolimod (IMO-2125) is a class B synthetic phosphorothioate oligonucleotide and a selective TLR9 agonist with potent immunostimulatory activity.”
In this open-label study, researchers enrolled 481 patients with unresectable, stage III/IV melanoma who experienced disease progression after treatment with a PD-1 inhibitor. Patients were randomized on a 1-to-1 basis to receive either 9 intratumoral injections of tilsotolimod over 24 weeks plus 3 mg/kg of ipilimumab once every 3 weeks starting week 2 (n = 238) or ipilimumab alone (n = 243). Primary end points included objective response rate (ORR) and overall survival (OS). Key secondary end points included progression-free survival (PFS), disease control rate, and safety.
At analysis, ORR was 8.8% in the tilsotolimod plus ipilimumab arm and 8.6% in the ipilimumab monotherapy arm. Median OS was 11.6 months and 10 months (hazard ratio [HR] 0.96; 95% confidence interval [CI], 0.77 to 1.19; P = .7), respectively. Median PFS was 2.9 months in the tilsotolimod plus ipilimumab arm and 2.7 months in the ipilimumab monotherapy arm. Disease control rates were 34.5% and 27.2%, respectively.
Grade ≥3 treatment-emergent adverse events occurred in 61.1% of patients in the tilsotolimod plus ipilimumab arm and 55.5% of patients in the ipilimumab monotherapy arm. The most common events in the tilsotolimod plus ipilimumab arm included pyrexia (46.2%), asthenia (34.6%), chills (32.1%), diarrhea (30.3%), pruritus (24.4%), nausea (23.5%), and fatigue (20.5%). The most common events in the ipilimumab monotherapy arm included diarrhea (28%), pruritus (25.4%), asthenia (23.3%), and nausea (20.3%).
“Although the tilsotolimod plus ipilimumab treatment did not meet its coprimary end point, these results are a valuable addition to the literature with respect to second-line treatment options in this disease area,” concluded Dr Diab et al.
“For patients with metastatic melanoma who progress on PD-1 checkpoint, the addition of ipilimumab remains the standard of care,” added Journal of Clinical Oncology associate editor Gary Schwartz, MD, Memorial Sloan Kettering Cancer Center, New York, New York.
Source:
Diab A, Ascierto PA, Maio M, et al. Randomized, open-label, phase III study of tilsotolimod in combination with ipilimumab versus ipilimumab alone in patients with advanced refractory melanoma (ILLUMINATE-301). J Clin Oncol. Published online: March 6, 2025. doi: 10.1200/JCO.24.00727
