Efficacy, safety, and cytokine profiling with addition of the toll-like receptor (TLR) 7/8 dual agonist EIK1001 to standard of care (SOC) first-line (1L) therapy: The phase 2 TeLuRide-005 trial in stage 4 NSCLC.

Abstract

8568 Background: EIK1001 a TLR 7/8 dual agonist activates dendritic cells via both innate and adaptive pathways. This mechanism of action (MOA) associated with cytokine (CK) release and T-cell differentiation is complementary to immune checkpoint inhibitors (ICIs) that enhance anti-tumor T-cell activity. It provides rationale to add EIK1001 to SOC chemotherapy (chemo) + ICI in Stage 4 NSCLC, a disease with unmet therapeutic needs. Methods: TeLuRide-005 (NCT#06246110) is an ongoing multicenter, open-label study of intravenous weekly (wk) EIK1001 combined with SOC q3-wk pembro + chemo in treatment-naïve patients (pts) with Stage 4 NSCLC. The nonsquamous (NSQ) and squamous (SQ) cohorts completed accrual in May ’25 and Jan ’26, respectively. CK were sampled pre- and post EIK1001 treatment (PT) on Day 1 of Cycle (C) 1 and C4. Results: 71 pts (median age: 68, male:73%) were treated. An ORR of 61% and DCR of 90% were observed for the pooled study population. Cytokine release syndrome (CRS) events were of low grade: 4 pts with Grade 1 and 3 pts with Grade 2. For safety, and efficacy by histology, see Table. 71% of NSQ remain progression free at 8 months and despite over 11 months of follow-up, median PFS is not yet accurately estimable. Type 1 and 2 interferons (IFN) and Interleukin 6/8 (IL6/8) increased PT on C1. By C4, baseline IP-10, an IFN inducible protein that is a T-cell chemotactant, was upregulated by a median of 1.6- fold increase from baseline C1D1. Conversely, CRS-associated IL6 and IL8 were reduced or less inducible on C4D1 than on C1D1, consistent with our observation of only one pt. experiencing CRS after C4. Conclusions: 1L EIK1001 + SOC demonstrates encouraging efficacy in Stage 4 NSCLC with evidence of durable effect. AEs were similar to SOC alone and CRS events were low-grade. Cytokine data support the MOA of the TLR 7/8 dual agonist, EIK1001, and reduced inducibility of IL6/IL8 PT by C4 may suggest CRS likelihood diminishes with time. Clinical trial information: NCT#06246110 . Safety Results At least 1 ≥ Grade 3 TEAE % (n/N) 76.1% (54/71) Serious adverse event (SAE) % (n/N) 46.5% (33/71) Efficacy Results NSQ (n=39) SQ (n=32) Months of follow up (f/u), median (range) 11.2 (5.5-23.0) 6.5 (0.5-19.1) Progression-Free Survival at 8 months* (95% CI) 70.7% (56.9-87.8%) NA Objective Response Rate** (ORR), % (95% CI) 55.6% (38.1-72.1%) 68.0% (46.5-85.1%) Disease Control Rate (DCR), % (95% CI) 83.3% (67.2-93.6%) 100% (86.3-100%) Duration of Response (DOR), Range in Months 2.1+ - 15.1+ 1.0 - 13.2+ NA: Not Analyzed due to short duration of follow-up; *4 scan opportunities at 8 months; **Response evaluable.