A phase 2/3 study of EIK1001 in combination with pembrolizumab and chemotherapy in participants with stage 4 non–small cell lung cancer (NSCLC) (TeLuRide-008).

TPS8668 Background: Immune checkpoint inhibitors (ICIs) reverse tumor-induced immune suppression and promote effective anti-tumor T-cell responses. Current standard of care (SOC) for Stage 4 NSCLC combining ICIs (e.g. pembrolizumab pembro) plus histology-appropriate chemotherapy (chemo) confers significant clinical benefit over chemo alone, yet many patients progress nonetheless, highlighting a large unmet medical need in this disease. EIK1001, a Toll-like receptor (TLR) 7/8 dual agonist, activates myeloid and plasmacytoid dendritic cells stimulating innate and adaptive immunity. In completed Phase 1 and ongoing Phase 2 studies, EIK1001 exhibits a manageable safety profile and encouraging anti-tumor activity both as monotherapy and in combination with ICIs. Methods: TeLuRide-008 (NCT#07365319) is a global, multicenter, randomized, double-blind, placebo-controlled, adaptive Phase 2/3 study of EIK1001 or placebo, in combination with pembro and histology-appropriate chemo in systemic-therapy-naïve pts with stage 4 NSCLC. In Phase 2, pts are randomized 1:1:1 to receive 1 of 2 doses of EIK1001 or placebo, + pembro and chemo (Part 1:Dose optimization; n~120), followed by additional enrollment with 1:1 randomization of new pts (n~160), at the EIK1001 selected dose or placebo (Part 2: Dose Expansion; n~280). If the study proceeds to Phase 3 (Part 3: Confirmatory), ongoing Phase 2 pts to continue treatment, and n~440 new pts will be randomized 1:1 to receive the selected dose of EIK1001 or placebo, + pembro and chemo (n = up to 750). Key eligibility criteria: pts ≥ 18 years of age, life expectancy ≥ 3 months, stage 4 NSCLC (NSQ or SQ), no actionable mutations requiring targeted therapy, ≥ 1 measurable lesion per RECIST v1.1, and no history of symptomatic pneumonitis. Primary objectives: evaluate efficacy and safety of 2 doses of EIK1001 + pembro and chemo for dose optimization and compare PFS (RECIST v1.1 by BICR) and OS between the selected EIK1001 dose and placebo, + pembro and chemo. Secondary objectives: safety and tolerability, ORR and DOR per RECIST v1.1 by BICR. Exploratory objectives: time to response, EIK1001 exposure-response relationships, and health-related quality of life. Clinical trial information: NCT#07365319 .