A First-In-Human Phase 1 Study Of Anticancer Stem Cell Agent Omp-54f28 (Fzds-Fe), Decoy Receptor For Wnt Ligands, In Patients With Advanced Solid Tumors

2505 Background: The WNT/FZD signaling pathway is implicated in tumor cell de-differentiation and cancer stem cell (CSC) function in numerous cancer types. As a first-in-class recombinant fusion protein, OMP-54F28 binds WNT ligands and blocks WNT signaling through its domain of an extracellular part of human Frizzled 8 receptor (fused to a human IgG1 Fc fragment). In patient-derived xenograft models, OMP-54F28 inhibits growth and CSC frequency, promotes differentiation of tumor cells, and synergizes with chemotherapy in a broad spectrum of malignancies. Methods: A 3+3 design was used; OMP-54F28 was given intravenously every 3 weeks. Objectives were determination of maximum tolerated dose (MTD), safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy. Results: 25 patients were treated in 7 dose-escalation cohorts (0.5, 1, 2.5, 5, 10, 15 and 20 mg/kg). No further dose escalation was pursued as animal data and PK modeling indicated 10 mg/kg as the target efficacious dose. Most common related Grade...