Adaptive phase 2/3 study of EIK1001, a TLR7/8 dual agonist, in combination with pembrolizumab, as first-line therapy in participants with advanced melanoma (TeLuRide-006).

Abstract

TPS9601 Background: Immune checkpoint inhibitors (ICIs), including anti-PD-1 antibodies, reverse tumor induced immune suppression and promote effective anti-tumor T-cell responses. They have drastically improved outcome in advanced melanoma therapy, yielding durable improvements in progression-free survival (PFS) and overall survival (OS). Although adding anti-CTLA-4 or anti-LAG-3 enhances efficacy beyond anti-PD-1 alone, these approaches do not directly target dominant myeloid-mediated resistance mechanisms within the tumor microenvironment, and new agents targeting this axis are needed. EIK1001, a TLR7/8 dual-agonist, activates myeloid and plasmacytoid dendritic cells to stimulate innate inflammation and adaptive immunity. Across multiple studies, EIK1001 has been well tolerated and has demonstrated clinical activity both as monotherapy and in combination with ICIs. Methods: TeLuRide-006 (NCT#06697301) is a global, multicenter, randomized, double-blind, adaptive Phase 2/3 trial of EIK1001 or placebo, in combination with pembrolizumab (pembro), as first-line therapy for participants (pts) with advanced cutaneous melanoma. Approximately 740 pts will be randomized, including a dose-optimization (DO) stage in which pts are randomized 1:1:1 to two EIK1001 dose levels or placebo, each administered with pembro, followed by Phase 2/3 expansion evaluating the selected EIK1001 dose versus placebo, with pembro. Interim analyses will guide progression from DO to Phase 2 and subsequently to Phase 3. EIK1001 or placebo is administered IV QW until the end of Week 27 then Q3W; while pembro is administered IV Q3W. Pts are stratified by prior anti-PD-1 adjuvant therapy, LDH level, and BRAF mutational status. Key eligibility criteria include patients ≥12 years (with country-specific variations), life expectancy ≥3 months, unresectable Stage III or Stage IV melanoma, known BRAF V600 status, at least one RECIST v1.1–measurable lesion, and no prior or current pneumonitis/interstitial lung disease. Primary objectives are to assess the efficacy and safety of two EIK1001 doses with pembro in DO, and to compare PFS (RECIST v1.1 by blinded independent central review [BICR]) and OS between the selected EIK1001 dose and placebo in combination with pembro. Secondary objectives include safety and tolerability of either EIK1001 dose with pembro, objective response rate and duration of response per RECIST v1.1 by BICR. Exploratory objectives include time to response, EIK1001 exposure-response relationships, and health-related quality of life. This study enrolled (randomized) its first participant on 5/21/2025 and is activated at 91 sites in 22 countries at the time of abstract submission.