Phase 1 study of bispecific HER2 antibody-drug conjugate MEDI4276 in patients with advanced HER2-positive breast or gastric cancer

Abstract

Background: MEDI4276 is a HER2-bispecific antibody targeting two different epitopes on HER2, with site-specific conjugation via maleimidocaproyl linker to a potent tubulysin-based microtubule inhibitor. MEDI4276 demonstrates enhanced cellular internalization and cytolysis of HER2+ tumor cells in vitro, including T-DM1 resistant cells.Methods: This was a phase 1 dose escalation trial in patients with advanced HER2+ breast or gastric cancer that was relapsed or refractory to standard therapy. MEDI4276 was infused intravenously over 60-90 minutes at 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.75, or 0.9 mg/kg every 3 weeks. Primary endpoints were safety and tolerability; secondary endpoints included antitumor activity (RECIST 1.1; ORR, PFS, and OS), pharmacokinetics (PK), and immunogenicity.