A Phase 1, Open-Label, Multi-Center, Multiple-Dose, Dose-Escalation Study of MDX-1342 in Patients with CD19-Positive Refractory/Relapsed Chronic Lymphocytic Leukemia.

Abstract 3425

Poster Board III-313

MDX-1342 is a fully human monoclonal antibody (HuMAb) with enhanced antibody-dependent cellular cytotoxicity (ADCC) effector function, targeting CD19-membrane receptor which is highly expressed on malignant chronic lymphocytic leukemia (CLL) cells. An open-label, multi-center, multiple-dose, dose-escalating Phase 1 study is being conducted to determine the safety and tolerability profile of MDX-1342 in subjects with CD19-positive relapsed or refractory CLL. To date, MDX-1342 has been administered intravenously (iv) weekly for 4 weeks to 12 subjects (8 Male, 4 Female) - in cohorts of 3 subjects each - at doses of 0.7, 7, 40, and 200 mg/dose. Overall, MDX-1342 has been well tolerated. No drug-related serious adverse events have been reported among the 12 subjects treated. Grade 1 and 2 infusion reactions (including rigors, chills, and wheezing) have been observed in 9 subjects. This has been adequately managed with the use of antihistamines and corticosteroids. Dose escalation continues and a maximum tolerated dose has not yet been identified. Of the 9 currently evaluable subjects, 1 has experienced a partial response (40 mg/dose cohort), 6 have stable disease and 2 have discontinued due to progressive disease. Preliminary results indicate antileukemic signals with dose-correlative reductions in both white blood counts (WBC) and circulating CD20+ cells after one 4-week cycle of weekly i.v. infusions of MDX-1342. In the 40 mg/dose cohort, the median reduction in WBC was 62% and the median reduction in circulating CD20+ cells was 74%. Additional subjects are being accrued to higher dose cohorts to more accurately characterize the safety and clinical activity of MDX-1342 and to determine if there is a consistent cumulative drop in WBC and circulating CD20+ cells as the dose increases.