Phase Ia study to evaluate RO7497987, a FLT3L-fragment Fc fusion protein, in healthy volunteers

BACKGROUND: Dendritic cells play a critical role in immunity. Fms‐related tyrosine kinase 3 ligand (FLT3L) is a cytokine that can promote the expansion and differentiation of bone marrow dendritic cells (DC) progenitors. RO7497987 (FLT3L‐Fc) is a novel FLT3 agonist developed to extend the half‐life of FLT3L and induce expansion of peripheral blood DC. METHODS: This Phase Ia trial evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of RO7497987 in healthy volunteers. Forty‐four participants received RO7497987 as a single ascending dose (SAD, 0.7‐70 mg) or multiple ascending doses (MAD, 7 or 21 mg, 21 days apart). RESULTS: RO7497987 was safe and well‐tolerated at all doses. The most common treatment‐related adverse events (AE) were Grade 1 myalgia, headache, and lymphadenopathy, all of which resolved spontaneously. There were no Grade ≥ 3 AEs, serious AEs, or dose‐limiting adverse events. Pharmacokinetic analysis showed dose‐dependent increases in FLT3L‐Fc Cmax and AUCinf with no accumulation in the MAD cohorts. RO7497987 administration resulted in dose‐dependent expansion of monocytes, as well as expansion of all major DC subsets, including conventional and plasmacytoid DC, which was sustained with multiple doses. CONCLUSION: These findings aid the design of dosing regimens of RO7497987 as an immunomodulatory agent. CLINICAL TRIAL REGISTRATION: https://www.isrctn.com/ISRCTN92655801, identifier ISRCTN92655801.