First-in-human, phase 1, open-label study of alomfilimab, an anti-ICOS antibody, as a single agent and in combination with anti-PD-L1 in advanced malignancies.

backgroundImmunosuppression mechanisms mediated by regulatory T cells (T

methodsAlomfilimab was administered intravenously once every 3 weeks (Q3W) ±3 days at six dose levels (DLs; 0.8 mg to 240 mg) as monotherapy and five DLs (0.8 mg to 80 mg) in combination with atezolizumab (1,200 mg Q3W ±3 days). Eligible patients must have had advanced metastatic disease as determined by Response Evaluation Criteria in Solid Tumors V.1.1 and no viable treatment options according to National Comprehensive Cancer Network guidelines.

resultsOverall 38 patients were enrolled in the monotherapy cohort, and 102 patients were enrolled in the combination therapy cohort. Alomfilimab had a manageable safety profile and showed a trend toward modest efficacy in tumor growth control when combined with anti-PD-L1 in selected malignancies. At least one treatment-emergent adverse event was reported in 35 patients (89.7%) in the monotherapy cohort, and in 99 (98%) patients in the combination cohort. Objective response was not observed in the monotherapy cohort. In the combination cohort, seven patients had an objective response. Median time to progression-free survival was 2 months for both cohorts. Furthermore, alomfilimab showed evidence of target engagement on T-cell subsets, specifically cluster of differentiation (CD)4+memory cells, in both single-agent and in combination treatment with atezolizumab. This was accompanied by transient elevation of granulocyte-macrophage colony-stimulating factor, interferon-γ, and tumor necrosis factor-α levels and dose-dependent reduction of ICOS+T

conclusionsAlomfilimab treatment was associated with an acceptable safety profile across both mono and combination approaches, accompanied by decreased ICOS+T TRIAL REGISTRATION NUMBER: NCT03829501.