Article Text
Abstract
Introduction Interleukin 12 (IL-12) strongly activates T and NK cells to produce IFNγ and kill tumor cells, yet has had limited success as an immunotherapeutic drug due to inefficient tumor targeting, short PK, and subsequent toxicity. We developed SON-1010, a single-chain native IL-12 genetically linked to a fully-human albumin binding (FHAB®) domain that targets the tumor microenvironment (TME) through albumin binding to over-expressed FcRn, GP60, and SPARC. This results in improved PK, decreased toxicity, and a broader therapeutic index. A ‘cold’ mouse melanoma model showed efficacy and significant increases in activated NK, NKT, Th1, and cytotoxic CD8 T cells. We hypothesize that SON-1010 may ‘warm up’ the TME to improve checkpoint inhibitor effectiveness in immunologically-active tumors like PROC that have high levels of SPARC.
Methods Study SB221 is a Phase 1b/2a multicenter study to assess the safety, tolerability, PK, PD, and efficacy of SON-1010 administered SC, either alone or in combination with a fixed dose ofatezolizumab (Tecentriq®) given IV (NCT05756907). Part 1 determines the maximum tolerated dose (MTD) of the combination in advanced solid tumors with expansion in PROC to establish the Recommended Phase 2 Dose (RP2D). Once the likelihood of efficacy is shown with a Simon 2-stage design, Part 2 will then assess the potential for improved efficacy of the combination of SON-1010 with atezolizumab versus the standard of care (SOC) in PROC. z
Current Trial Status The first dose-escalation cohorts have been enrolled and additional sites are being added to help with recruitment of patients with PROC.