First-in-human phase 1a/1b study of LB-LR1109, an anti-LILRB1 monoclonal antibody, as monotherapy in advanced solid tumors and in combination with atezolizumab in advanced NSCLC.

TPS2668 Background: LB-LR1109 is a human IgG4 monoclonal antibody targeting LILRB1, an inhibitory receptor expressed on multiple immune cell subsets. LILRB1 binds HLA-G, delivering suppressive signals that enable tumor immune evasion. Blocking this axis may restore immune activation within the tumor microenvironment and promote both innate and adaptive anti-tumor responses. Phase 1a tumor types were selected through TCGA analyses showing high LILRB1/HLA-G expression and increased infiltration of LILRB1+ NK cells, T cells, and monocytes in RCC, NSCLC, HNSCC, urothelial carcinoma (UC), and melanoma. High LILRB1 expression correlates with poor overall survival in RCC, UC, and lung SCC, supporting clinical relevance. Preclinical data (AACR2026 #1243) demonstrated that LB-LR1109 binds LILRB1 with high affinity, blocks HLA-G interactions, restores NK and T-cell function, and induces strong anti-tumor activity in human LILRB1 transgenic mouse models. LB-LR1109 also showed synergy with PD-L1 blockade, favorable PK, and an excellent safety profile, supporting clinical development as monotherapy and in combination. Public transcriptomic data also support combining LB-LR1109 with atezolizumab in NSCLC based on correlated LILRB1 and PD-L1 expression. Methods: This ongoing first-in-human, multicenter, open-label Phase 1 study (NCT06332755) evaluates LB-LR1109 as monotherapy (Phase 1a) and in combination with atezolizumab (Phase 1b). The study began in September 2023; Phase 1b enrollment started December 2025. Phase 1a includes monotherapy dose escalation (DL1–DL8, IV Q2W) using BLRM, enrolling patients with advanced/metastatic RCC, NSCLC, HNSCC, UC, or melanoma who relapsed from or are intolerant to approved therapies. Phase 1b evaluates LB-LR1109 (IV Q2W) plus atezolizumab 840 mg Q2W in advanced/metastatic NSCLC without actionable mutations. Patients must have received prior approved therapies including anti-PD-1/PD-L1 with ≥12 weeks of response, to test whether LILRB1 blockade may restore immune surveillance after checkpoint inhibitor resistance. Primary objectives: safety, tolerability, and determination of MTD/RP2D. Secondary endpoints: antitumor activity, PK, immunogenicity. Exploratory endpoints: correlations between LILRB1/HLA-G expression and clinical response, longitudinal immune profiling, and receptor occupancy in peripheral monocytes. The study is conducted at eight sites in Korea and the United States. Phase 1a has escalated to DL7 with no DLTs, and enrollment into the combination DL5 cohort began January 2026. Clinical trial information: NCT06332755 .