A phase 1, open-label, dose-escalation study of BIIB022 (anti-IGF-1R monoclonal antibody) in subjects with relapsed or refractory solid tumors.
OBJECTIVE
The IGF-1R signaling pathway has been implicated in multiple cancers as important for cell survival, proliferation, invasion and metastasis. BIIB022 is a non-glycosylated human IgG4 monoclonal antibody (mAb) with specificity for IGF-1R. Unlike other anti-IGF1R antibodies, BIIB022 has no effector functions. Additionally, inhibition is via an allosteric rather than competitive mechanism, which further differentiates this antibody from others. We sought to determine the safety and tolerability of BIIB022 and determine the pharmacokinetic (PK) and pharmacodynamic (PD) profile of this antibody.


METHODS
A multi-institutional phase I study evaluated the safety of escalating doses of BIIB022 given IV q3wk until progression or unacceptable toxicity in patients with advanced solid tumors. Five sequential BIIB022 dose cohorts were evaluated using a standard 3 + 3 dose-escalation design (1.5, 5. 10, 20, 30 mg/kg); 10 additional patients were treated at the recommended phase 2 dose.


RESULTS
34 patients were treated. Toxicities were manageable and mostly low grade; grade 3-4 hyperglycemia was not observed. No RECIST responses were observed, although three patients had metabolic responses associated with prolonged stable disease. The PK of BIIB022 was nearly linear in the dose range from 10 to 30 mg/kg, with some nonlinearity at lower doses (1.5-5.0 mg/kg), likely due to target-mediated drug disposition of BIIB022 at low serum concentrations. PD analyses showed decrease in IGF-1R levels on leucocytes, with stable serum values of IGF-1 and IGF-2.


CONCLUSIONS
BIIB022 can be safely given at 30 mg/kg IV every 3 weeks with preliminary evidence of biological activity in selected patients.
Fox Chase Cancer Center, Philadelphia, PA, USA, Margaret.vonMehren@fccc.edu.
Margaret
M
von Mehren
Carolyn D
CD
Britten
Peter
P
Pieslor
Wayne
W
Saville
Artemios
A
Vassos
Sarah
S
Harris
Gerald R
GR
Galluppi
Mohamed
M
Darif
Zev A
ZA
Wainberg
Roger B
RB
Cohen
Stephen
S
Leong
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C000594951:BIIB022; D017526:Receptor, IGF Type 1