First-in-Human Phase I Trial of a Tumor-Targeted Cytokine (NHS-IL12) in Subjects with Metastatic Solid Tumors.

ABSTRACT: PURPOSE:The NHS-IL12 immunocytokine is composed of two IL12 heterodimers fused to the NHS76 antibody. Preclinical studies have shown that this antibody targets IL12 to regions of tumor necrosis by binding histones on free DNA fragments in these areas, resulting in enhanced antitumor activity. The objectives of this phase I study were to determine the maximum tolerated dose (MTD) and pharmacokinetics of NHS-IL12 in subjects with advanced solid tumors. PATIENTS AND METHODS:Subjects (n = 59) were treated subcutaneously with NHS-IL12 in a single ascending-dose cohort followed by a multiple ascending-dose cohort (n = 37 with every 4-week dosing). RESULTS:The most frequently observed treatment-related adverse events (TRAE) included decreased circulating lymphocytes, increased liver transaminases

SUBMITTER: Strauss J 

PROVIDER: S-EPMC6320276 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature