Phase I pharmacokinetics (PK) of humanized anti-MUC-1 antibody R1550

2533 Background: MUC-1 glycoprotein establishes a molecular barrier at the epithelial surface, and engages in morphogenetic signal transduction. A 20 amino acid MUC-1 core tandem repeat is aberrantly glycosylated in >90% of epithelial tumors, exposing peptide sequence PDTRP. Humanized IgG1 κ monoclonal antibody R1550 binds PDTRP (Kd∼1nM) and induces potent antibody-dependent cellular cytotoxicity. Methods: R1550 clinical tolerability and PK was determined in advanced, PDTRP-expressing (by IHC), breast cancer patients progressing after anthracyclines and taxanes. Key eligibility: informed consent, WHO PS 0–1, life expectancy >4 mos, non-inflammatory histology, and no CNS metastasis. R1550 was infused IV over 1–3 hrs: cohort 1 (N = 3) 1 mg/kg; cohort 2 (N = 9) 3 mg/kg; cohort 3 (N = 6) 9 mg/kg; cohort 4 (N=3) 16 mg/kg, with repeat dosing every 1–2 weeks (patient-individualized PK assessment) until disease progression. Plasma [R1550] was measured by quantitative ELISA. PK parameters were analyzed by a non-co...