A phase 2 study of EIK1001, a Toll-like receptor 7/8 (TLR7/8) agonist, in combination with pembrolizumab and chemotherapy in patients with stage 4 non-small cell lung cancer.

Abstract

TPS8667 Background: Immune checkpoint inhibitors (ICIs) relieve immunosuppression of tumor-reactive T cells and enhance antitumor immune response. Significant advances for the treatment of non-small cell lung cancer (NSCLC) have been made using the ICI pembrolizumab in combination with chemotherapy, which confers significant clinical benefit relative to chemotherapy and placebo. Not all patients benefit, however, and some become refractory. As a result, there remains a critical unmet need to develop therapies for the treatment of NSCLC. EIK1001 is a TLR7/8 agonist that stimulates myeloid and plasmacytoid dendritic cells, activating immune and inflammatory responses. This dual activity provides another pathway, distinct from effects on checkpoint proteins, to enhance antitumor T-cell activity alone or in combination with ICIs. Methods: Study EIK1001-005 is a multicenter, Phase 2, open-label study of EIK1001 in combination with pembrolizumab and chemotherapy – carboplatin plus either pemetrexed or paclitaxel – in participants (pts) with histologically confirmed Stage 4 nonsquamous or squamous NSCLC, respectively. This study includes a safety run-in period for pts enrolled in each NSCLC cohort. If < 2 dose-limiting toxicities occur, an expansion phase for each NSCLC cohort will be conducted at the target dose to evaluate the tolerability and efficacy of EIK1001 (QW) in combination with pembrolizumab and chemotherapy (administered Q3W per label). Key eligibility criteria include pts ≥ 18 years of age with a life expectancy of at least 3 months, histologically or cytologically confirmed Stage 4 NSCLC (nonsquamous or squamous) without prior therapy for advanced NSCLC, confirmation that mutation-directed therapy is not indicated as first-line, and at least 1 measurable lesion at Baseline according to RECIST 1.1. The primary objective of this study is to determine the safety and tolerability of EIK1001 in combination with pembrolizumab and chemotherapy. The secondary objectives are evaluation of antitumor activity by objective response rate (ORR; defined as the proportion of pts who have a confirmed complete response [CR] or partial response [PR] per RECIST 1.1) and duration of response (DOR) by RECIST 1.1. Other exploratory objectives include evaluation of anti-tumor activity (ORR/DOR) by immune-related RECIST 1.1, overall survival, progression-free survival, investigation of the relationship between treatment with EIK1001 in combination with pembrolizumab/chemotherapy and biomarkers predictive of response, and the pharmacokinetic parameters of EIK1001. This study opened on 29 Jan 2024. Clinical trial information: NCT06246110 .