Tilsotolimod Demonstrates Encouraging Activity, Safety in Early-Stage Melanoma

Pipeline Report: May 2022

The synthetic Toll-like receptor 9 agonist tilsotolimod reduced the sentinel lymph node biopsy positivity rate vs placebo in patients with localized, excised melanoma.

Vincent Milano

Vincent Milano

The synthetic Toll-like receptor 9 agonist, tilsotolimod (IMO-2125), reduced the sentinel lymph node (SLN) biopsy positivity rate vs placebo in patients with localized, excised melanoma, according to interim data from the phase 1 INTRIM-1 trial (NCT04126876).1

Results showed that patients who received an injection of tilsotolimod following the excision of a primary tumor achieved a 70% lower SLN positivity rate vs those who were injected with placebo. Notably, the SLN positivity rate for patients who received the placebo was between 40% and 50%.

“This is an exciting result from tilsotolimod, and we are pleased for the patients and their families to whom it offers hope for the future,” Vincent Milano, chief executive officer, Idera Pharmaceuticals, Inc., stated in a press release. “These results, together with data supporting tilsotolimod’s mechanism of action and encouraging safety profile from across the array of earlier preclinical and clinical work, reinforce the potential of tilsotolimod to offer benefit to patients with certain cancers. As a result, we plan to actively pursue a strategic partnership for tilsotolimod so that its full potential for patients may continue to be explored.”

INTRIM-1 enrolled patients who were at least 18 years of age and who had histologically confirmed primary malignant melanoma cutis with a Breslow tumor depth that was greater than 2 mm.2 To be eligible for enrollment, patients needed to have a pathological tumor stage of 3 or 4 with no regional metastases detected and no evidence of distant metastasis; they also needed to have a World Health Organization performance status of 0 or 1.

Patients must have been scheduled to undergo excision and sentinel node biopsy, and have agreed to use effective contraceptive methods from screening until at least 90 days after the administration of tilsotolimod.

Key exclusion criteria included known hypersensitivity to any oligodeoxynucleotide, active autoimmune disease requiring disease-modifying therapy at the time of screening, pathologically confirmed locoregional or distant metastasis, non-skin melanoma, the presence of another primary malignancy, and active systemic infections requiring antibiotics.

Once randomized, patients received tilsotolimod, which was administered via intradermal injection at 8 mg, or placebo, given at the primary excision site. The SLN biopsy was conducted 7 to 10 days following treatment.

The primary end point of the trial was rate of tumor-positive SLNs at the time of biopsy. A key secondary end point was immune response in the SLN and peripheral blood 7 to 10 days after biopsy, as measured by frequency and activation state of lymph node resident conventional dendritic cells and melanoma antigen-specific T cell responses in the SLN and peripheral blood. Other secondary end points included relapse-free survival and overall survival at 5 years and 10 years following biopsy.

Previously reported data from an early analysis done by flow cytometry of the SLN biopsies in those enrolled to INTRIM 1 showed immune activation with the use of tilsotolimod, including elevated frequencies of key dendritic cells.

The trial will continue to evaluate RFS and OS at 5 and 10 years after SLN biopsy. Full data from the trial will be presented at an upcoming medical meeting.

“Currently, there are limited adjuvant treatments available to improve survival after surgical excision of a primary melanoma,” Tanja de Gruijl, PhD, professor at Amsterdam University Medical Centers, stated in a press release. “We are delighted with the results we have seen in this study, which suggest that tilsotolimod administered at the excision site lowers the extent of tumor-positive lymph nodes and, if it improves overall survival, offers early melanoma patients a potential new treatment option.”

Tilsotolimod was previously evaluated in combination with ipilimumab (Yervoy) in patients with advanced melanoma who were refractory to a PD-1 inhibitor, as part of the phase 2 ILLUMINATE-301 trial (NCT03445533), although the combination failed to improve overall response rates compared with ipilimumab alone.3


  1. Idera pharmaceuticals shares positive results from investigator-sponsored trial in melanoma patients at Amsterdam UMC. News release. Idera Pharmaceuticals, Inc. May 17, 2022. Accessed May 19, 2022. https://bit.ly/38HUShj
  2. A randomized controlled phase II trial with intradermal IMO-2125 in pathological tumor stage (p) T3-4 cN0M0 melanoma (INTRIM). ClinicalTrials.gov. Updated April 15, 2021. Accessed May 19, 2022. https://clinicaltrials.gov/ct2/show/NCT04126876
  3. Idera Pharmaceuticals announces results from ILLUMINATE-301 trial of tilsotolimod + ipilimumab in anti-PD-1 refractory advanced melanoma. News release. Idera Pharmaceuticals, Inc. March 18, 2021. Accessed May 19, 2022. http://bit.ly/3r5gxDg
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