Phase I Study of Simlukafusp Alfa (FAP-IL2v) with or without Atezolizumab in Japanese Patients with Advanced Solid Tumors.

Purpose: The aim of the study was to evaluate the safety/tolerability and pharmacokinetics of simlukafusp alfa (FAP-IL2v), an immunocytokine containing an anti-fibroblast activation protein-α (FAP) antibody and an IL2 variant, administered alone or with the PDL1 inhibitor atezolizumab, in Japanese patients with advanced solid tumors.

Patients And Methods: In this phase 1, open-label, dose-escalation study, patients received i.v.

Iron complexes capped with dendrimer-appended triazacyclononanes as the novel spatially encumbered models of non-heme iron proteins.

Poly(benzyl ether) dendrimers with a 1,4,7-triazacyclononane (TACN) focal core (Ln(3)TACN, 2a-4a) and nondendritic L1(3)TACN (1a), upon reaction with FeCl(2), followed by NaOAc and NH(4)PF(6), afforded mononuclear iron(II) complexes [Fe(II)(eta(2)-OAc)(Ln(3)TACN)](+) (1b-4b), which were oxidized under O(2) to form dinuclear (mu-O)(mu-OAc)(2)diiron(III) complexes (1c-4c) in 54-74% isolated yields. The formation of 1c-4c obeyed second-order kinetics with respect to 1b-4b, respectively, where the observed rate constants (k(2)) were clearly dependent on the generation number of the dendritic substituents. Photoirradiation of 1c-4c in the presence of NaOAc gave diiron(II) complexes (1d-4d), which were reoxidized to 1c-4c by O(2), following first-order kinetics with respect to 1d-4d, respectively.