Pharmacokinetic and safety study of subcutaneously administered weekly ING-1, a human engineere monoclonal antibody targeting human EpCAM, in patients with advanced solid tumors.
BACKGROUND
ING-1 is a high-affinity, human engineeredtrade mark monoclonal antibody that recognizes a 40 kilodalton epithelial cell adhesion molecule (EpCAM) glycoprotein that is expressed in high levels on most adenocarcinomas and is an attractive target for immunotherapy.


METHODS
ING-1 was administered subcutaneously weekly at doses between 0.1 and 2 mg/kg/week. Pharmacokinetic samples were drawn during weeks 1 and 6.


RESULTS
Fourteen patients with advanced refractory cancer received a median of 6 (range 1-9) doses of ING-1. At 1 mg/kg, a 62-year-old man with colon cancer developed reversible grade 3 pancreatitis after the third dose. His plasma ING-1 levels were similar to the other two patients dosed at 1 mg/kg. Two patients dosed at 0.6 mg/kg experienced stable disease at 6 weeks. Peak drug levels increased with dose and time, suggesting drug accumulation with repeated dosing. Low human anti-human antibody response was noted in three of the 13 patients assessed and was directed towards the variable region of ING-1.


CONCLUSIONS
Weekly ING-1 administered subcutaneously was well tolerated at 0.6 mg/kg/week and further experience at this dose is warranted to demonstrate safety. The risk of pancreatitis and the marginal anti-tumor effect may preclude further monotherapy studies; however, combination studies with chemotherapy are warranted.
Goel
S
S
Albert Einstein Cancer Center, New York, NY, USA. sgoel@montefiore.org
Bauer
R J
RJ
Desai
K
K
Bulgaru
A
A
Iqbal
T
T
Strachan
B-K
BK
Kim
G
G
Kaubisch
A
A
Vanhove
G F
GF
Goldberg
G
G
Mani
S
S
D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000951:Antigens, Neoplasm / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; C479480:ING-1 monoclonal antibody, human