PURPOSE: CT-011 is a humanized IgG1 monoclonal antibody that modulates the 
immune response through interaction with PD-1, a protein belonging to the B7 
receptor family present on lymphocytes. The objectives of this phase I study 
were to assess the dose-limiting toxicities, to determine the maximum tolerated 
dose, and to study the pharmacokinetics of CT-011 administered once to patients 
with advanced hematologic malignancies.
EXPERIMENTAL DESIGN: Seventeen patients were treated with escalating doses of 
CT-011 ranging from 0.2 to 6 mg/kg. For pharmacokinetic analysis, blood samples 
were withdrawn from the patients before and immediately after treatment and at 
24 hours, 48 hours, and on days 7, 14, and 21. CT-011 blood levels were assessed 
with a specific ELISA and derived concentrations were used to calculate 
pharmacokinetic parameters. Activation of the immune system was assessed by 
measuring peripheral blood CD4+, CD8+, and CD69+ lymphocytes.
RESULTS: The study showed the antibody to be safe and well tolerated in this 
patient population. No single maximum tolerated dose was defined in this study. 
Clinical benefit was observed in 33% of the patients with one complete 
remission. Pharmacokinetic analyses show that serum Cmax and the AUC of CT-011 
increased proportionally with dose. The median t1/2 of CT-011 ranged from 217 to 
410 hours. Sustained elevation in the percentage of peripheral blood CD4+ 
lymphocytes was observed up to 21 days following CT-011 treatment.
CONCLUSIONS: A single administration of 0.2 to 6.0 mg/kg of CT-011 is safe and 
well tolerated in patients with advanced hematologic malignancies.