ILLUMINATE-204 Update: Promising Results Reported With Tilsotolimod Plus Ipilimumab in Advanced Melanoma

Positive efficacy was demonstrated with the toll-like receptor 9 agonist, tilsotolimod (IMO-2125) in combination with either ipilimumab (Yervoy) in patients with anti-PD-1 refractory advanced melanoma, according to final topline data from the phase I/II ILLUMINATE-204 trial announced in a press release from Idera Pharmaceuticals, Inc.

“The clinical benefit suggested for these anti-PD-1 refractory melanoma patients with limited treatment options includes stabilization of disease and even responses, which is creating hope that this combination might be of benefit to patients in the PD-1 refractory setting,” stated Joseph Markowitz, MD, PhD, from the H. Lee Moffitt Cancer Center & Research Center in Tampa, Florida. “We eagerly await the outcome of the ongoing phase 3 trial to see whether this combination treatment with ipilimumab will represent an additional option for patients with advanced melanoma.”

In the phase II portion of the 2-arm study, a total of 52 patients received tilsotolimod 8 mg plus ipilimumab 3 mg/kg. Of the patients in the tilsotolimod/ipilimumab arm, 49 were evaluable for the efficacy analysis.

The median overall survival (OS) for this group was 21.0 months (95% CI, 9.8-not reached [NR] months). The overall response rate (ORR), which was assessed per Response Evaluation in Solid Tumors (RECIST v1.1), was 22.4% (95% CI, 11.8%-6%), which included 2 complete responses (CRs). The disease control rate (DCR), which was defined as either stable disease or better, was 71.4% (95% CI, 56.7-83.4%).

The median duration of response was 11.4 months with tilsotolimod/ipilimumab (95% CI, 3.3 months-NR), with 7 out of 11 patients having responses for more than 6 months per RECIST v1.1. In terms of tumor size, reductions were observed in the tumor of patients who received an intratumoral injection and those who did not.

The majority of patients tolerated the combination well. Grade 3/4 treatment-emergent adverse events (TEAEs) were reported in 48% of patients. The most common TEAEs were autoimmune hepatitis, hyponatremia, and hypophysis, which each occurred in 2 patients. Immune-related toxicities were observed in 26% of patients, which may suggest that the addition of tilsotolimod to ipilimumab is not any more toxic to patients than ipilimumab alone. No TEAEs led to treatment discontinuation or death in the study.

ILLUMINATE-204 is a multicenter, 2-arm study being conducted in the United States. Phase I of the study is evaluating the safety of tilsotolimod plus ipilimumab or pembrolizumab (Keytruda) with the primary end point being the number of patients with TEAEs. The phase II portion of the study is evaluating efficacy with the primary end point being the number of patients with an objective response per RECIST v1.1.

Patients with a histologically confirmed diagnosis of metastatic melanoma with measurable, stage III, IVA, IVB, or IVC disease are eligible to enroll in the trial. These patients are required to have symptomatic or radiographic progression during or after treatment with a PD-1 or PD-L1 inhibitor, an ECOG performance status of 2 or lower, and adequate laboratory values. Phase I patients are required to have at least two biopsy accessible measurable tumor lesions ≥ 1.0 cm.

“The outcomes from this study encourage our belief that the combination of tilsotolimod and ipilimumab may provide a much-needed treatment option for advanced melanoma patients who have limited available therapies,” stated Elizabeth Tarka, MD, Idera’s chief medical officer. “We are looking forward to completing our registrational trial for this indication, ILLUMINATE-301, where a comparator arm is included, and moving this potential therapy one step closer to patients in need.”

To bring tilsotolimod closer to use in the clinical setting, the agent is currently under investigational in the phase III ILLUMINATE-201 study in combination with ipilimumab versus ipilimumab alone in patients with anti-PD1 refractory melanoma. The study is ongoing with a target number of 453 participants and a prospective completion date of September 2021.

^References

^{Idera Pharmaceuticals announces final clinical safety and efficacy data from illuminate-204 trial in advanced melanoma [news release]. Exton, Pennsylvania: Idera Pharmaceuticals; April 21, 2020. https://bit.ly/2yztkIw. Accessed April 21, 2020.}