A first‐in‐human study of the novel immunology antibody–drug conjugate, ABBV‐3373, in healthy participants.

Aims: ABBV‐3373, an immunology antibody–drug conjugate composed of adalimumab conjugated to a proprietary glucocorticoid receptor modulator (the small‐molecule payload), has the potential to treat immune‐mediated inflammatory diseases. This first‐in‐human study investigated the pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) using a safety PD marker, and safety/tolerability of ABBV‐3373 in healthy adults. Methods: Fifty‐five participants were randomly assigned to single‐dose subcutaneous (SC; 30, 100 or 300 mg) or intravenous (IV; 30, 300 or 900 mg) ABBV‐3373 or placebo. Eight additional participants received a single dose of 10 mg oral prednisone for evaluation of systemic glucocorticoid effects. Blood samples were collected for up to 85 days postdose for PK, anti‐drug antibody and serum cortisol (safety PD marker) assessments. Results: ABBV‐3373 and total antibody displayed antibody‐like SC/IV PK profiles and the unconjugated/free payload in circulation exhibited formation rate‐limited kinetics with exposure several fold lower than ABBV‐3373 or total antibody. Treatment‐emergent anti‐drug antibody incidence was 69%, with loss of exposure in 6% (SC) and 5% (IV) of participants, but without any impact on safety. ABBV‐3373 up to 300 mg SC/IV had no apparent impact on serum cortisol, and only caused a transient decrease at 900 mg IV. Treatment‐emergent adverse events were primarily mild in severity, and no pattern emerged with respect to dose or route of administration. Conclusions: ABBV‐3373 had favourable PK profiles, manageable immunogenicity, and was generally well‐tolerated. Except for a transient effect at 900 mg IV, there was no apparent impact on serum cortisol. Study results supported further clinical development of ABBV‐3373. [ABSTRACT FROM AUTHOR]