Clinical Pharmacology Strategies for Bispecific Antibody Development: Learnings from FDA‐Approved Bispecific Antibodies in Oncology

Abstract

Bispecific antibodies, by enabling the targeting of more than one disease‐associated antigen or engaging immune effector cells, have both advantages and challenges compared with a combination of two different biological products. As of December 2023, there are 11 U.S. Food and Drug Administration–approved BsAb products on the market. Among these, 9 have been approved for oncology indications, and 8 of these are CD3 T‐cell engagers. Clinical pharmacology strategies, including dose‐related strategies, are critical for bispecific antibody development. This analysis reviewed clinical studies of all approved bispecific antibodies in oncology and identified dose‐related perspectives to support clinical dose optimization and regulatory approvals, particularly in the context of the Food and Drug Administration's Project Optimus: (1) starting doses and dose ranges in first‐in‐human studies; (2) dose strategies including step‐up doses or full doses for recommended phase 2 doses or dose level(s) used for registrational intent; (3) restarting therapy after dose delay; (4) considerations for the introduction of subcutaneous doses; (5) body weight vs. flat dosing strategy; and (6) management of immunogenicity. The learnings arising from this review are intended to inform successful strategies for future bispecific antibody development.