TeLuRide-006: An adaptive phase 2/3 study of EIK1001, a Toll-like receptor 7/8 (TLR7/8) agonist, in combination with pembrolizumab in patients with advanced melanoma.

TPS9604 Background: Immune checkpoint inhibitors (ICIs) relieve immunosuppression of tumor-reactive T cells and enhance antitumor response. Significant advances for the treatment of advanced melanoma have been made using ICIs, with overall survival (OS) benefit conferred by ICI monotherapy. While encouraging results have been observed with combinations of ICIs, no α-controlled, statistically significant OS benefit of combinations over monotherapy has been demonstrated in Phase 3 studies. Despite these advances, 5-year survival for advanced disease is only 15 to 20%, motivating development of new therapies. EIK1001 is a TLR7/8 agonist that stimulates myeloid and plasmacytoid dendritic cells, activating immune and inflammatory responses. This dual activity, distinct from effects on checkpoint proteins, enhances antitumor T-cell activity alone or in combination with ICIs. Methods: TeLuRide-006 (NCT#06697301) is a global, multicenter, randomized, double-blind, adaptive Phase 2/3 study of EIK1001 or placebo in combination with pembrolizumab (pembro) as first-line therapy in participants (pts) with advanced melanoma. This study includes dose-optimization (DO), in which pts are randomized 1:1:1 to receive 1 of 2 doses of EIK1001 or placebo in combination with pembro, followed by adaptive Phase 2/3 expansion at the Selected Dose of EIK1001 + pembro or placebo + pembro. Interim analyses will determine whether the study advances from DO to Phase 2 to Phase 3. EIK1001 or placebo is administered intravenously QW until the end of Week 27 then Q3W. Pts are stratified by prior anti-PD-1 adjuvant therapy, LDH level, and BRAF mutational status. Key eligibility criteria: pts ≥ 18 years of age with a life expectancy of ≥ 3 months, Stage 3 (unresectable) or Stage 4 metastatic melanoma, known BRAF V600 mutational status (or consent to BRAF mutation testing), ≥ 1 measurable lesion by RECIST v1.1, and no history of or current pneumonitis/interstitial lung disease. Primary objectives are to evaluate the efficacy and safety of 2 doses of EIK1001 in combination with pembro (DO only) and to compare progression-free survival per RECIST 1.1 by blinded independent central review (BICR) and OS of pts receiving EIK1001 + pembro relative to pts receiving placebo + pembro (at Selected Dose). Secondary objectives include evaluation of the safety and tolerability of the Selected Dose of EIK1001 + pembro relative to placebo + pembro, as well as evaluation of objective response rate and duration of response per RECIST 1.1 by BICR. Exploratory objectives include evaluation of time to objective response, evaluation of potential EIK1001 exposure-response relationships, and evaluation of health-related quality of life, health utilities, and melanoma concerns in pts receiving EIK1001 + pembro relative to placebo + pembro. This study opened on 24 December 2024. Clinical trial information: 06697301 .