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blood samples were withdrawn from the patients before and immediately after treatment and at 24 hours, 48 hours, and on days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 C max and the AUC of CT-011 increased proportionally with dose. The median t 1/2 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.
