ATX-101 has a favorable safety profile
TEAE
HEPATOCELLULAR CARCINOMA, ADVERSE EVENT, ELEVATED CHOLESTEROL, ADVERSE EVENTS
DLT were not observed, and the maximum tolerated dose was not reached. With exception of one grade 3 adverse event (elevated cholesterol in a patient with hepatocellular carcinoma) only mild and moderate treatment-related adverse events were observed (Table Incidence of treatment-related TEAE that occurred in more than 1 patient.All listed TEAEs were CTCAE grade 1 or 2.Infusion-related reactions (IRR) were identified as the only specific adverse event of ATX-101. Two measures were implemented to prevent the occurrence of IRR: (i) a premedication comprising glucocorticoids, H1 and H2 blockers, diphenhydramine and montelukast, (ii) a stepwise increase of the infusion rate. Despite these measures, IRR were observed in 64% of the patients (Table Incidence and CTCAE grading of infusion-related reactions (IRR).n: number of patients with IRR; N: total number of IRRs.The reason for IRR has not been completely clarified. In vitro data from mast cells and data generated in dogs suggest a correlation of IRR with a transient increase in histamine levels induced by ATX-101 (unpublished data). Such increases of histamine could not be reproduced in this study because data from only 3 patients experiencing an IRR were available. Further investigations are ongoing in current clinical studies. The development of anti-drug antibodies is deemed to be unlikely because of the above-mentioned preclinical data and clinical data showing that IRR occurred in most patients during the first infusion and did not exacerbate during the treatment. In addition, peptide with cell penetrating, cationic parts are known to cause histamine release [