Imc-1121b and Imc-A12: Preliminary Clinical Experience with Anti-Vegfr2 and Anti-Igf-1r Antibodies
Schwartz Jonathan D
ImClone Systems, Inc., Branchburg, New Jersey, USA
IMC-1121B and IMC-A12 are human monoclonal IgG1 antibodies that target, respectively, the vascular endothelial growth factor receptor-2 (VEGFR2) and insulin-like growth factor receptor-1 (IGF-1R). Pre- clinical studies have demonstrated that these therapeutic antibodies confer growth inhibition in multiple in vitro and in vivo cancer models.
Phase 1 studies have been conducted testing the safety, tolerability, pharmacokinetics and preliminary efficacy of these agents in patients with advanced, refractory solid tumors.
Two phase 1 studies have assessed IMC-1121B at multiple weekly (2-16 mg/kg), q14 day (6-10 mg/kg) and q21 day (15-20mg/kg) doses in 61 patients. Hypertension has been the most frequently observed side effect associated with IMC-1121B and has been considered a dose limiting toxicity (grade 3) in a small number of instances. MTD has been determined as 13mg/kg/week and has not been reached for q14/q21 day dosi ng.
Pharmacokinetic analyses have indicated that serum trough levels observed with most doses exceed those associated with anti-tumor activity in pre-clinical tumor models.
IMC-1121B has been associated with substantial tumor control including several partial responses and multiple instances of stable disease lasting at least 5 months in the weekly dosing (n = 37) study. Multiple instances of stable disease >6 months have been observed on the every 2 and 3 week dosing study. Phase 2-3 studies are underway or planned in multiple solid tumors.
Two phase 1 studies have assessed IMC-A12 at multiple weekly (3-15 mg/kg) and q14 day (6-15 mg/kg) doses in 40 patients. Hyperglycemia has been the most frequently observed side effect associated with IMC-A 12 and has been considered a dose limiting toxicity (grade 3) in a small number of instances.
MTD has not been identified for weekly or q14 day dosing.
Pharmacokinetic analyses indicates that serum trough levels observed with most doses exceed those associated with anti-tumor activity in pre-clinical tumor models.
IMC-A 12 has been associated with multiple instances of stable disease lasting at least 6 months in the weekly dosing (n = 24) and q14 day (n = 16) studies. Phase 2 studies are underway or planned in multiple solid tumors.
