Phase I and pharmacokinetic study of etaracizumab (Abegrin), a humanized monoclonal antibody against alphavbeta3 integrin receptor, in patients with advanced solid tumors.
This study assessed the safety, immunogenicity, and pharmacokinetics of etaracizumab, a monoclonal antibody directed against the alphavbeta3 integrin, in patients with advanced malignancies. Four cohorts of four patients received escalating dose of etaracizumab as a 30-min intravenous infusion, first as a single test dose, followed-up 2-5 weeks later by weekly doses. Sixteen patients with advanced solid tumors received a total of 309 cycles of etaracizumab at doses ranging 1-6 mg/kg. The mean number of weekly infusions was 19 (ranging 5-53). Frequently reported adverse events were grades 1-2 asthenia (15 patients) and infusion reactions (9 patients). At 1 mg/kg, one patient experienced grade 3 chills with the first infusion. Other grade 3 toxicities included reversible hyponatremia, hypophosphatemia and hyponatremia in one patient each at 1, 4 and 6 mg/kg, respectively. No patient experienced treatment delay/discontinuation due to an adverse event. The half-life of etaracizumab ranged 49-180 h with a nonlinear increase in terminal half-life with increasing doses. There was no objective response but five patients experienced a stable disease of >6-month duration. Etaracizumab was well-tolerated at doses up to 6 mg/kg with no evidence of immunogenicity. The safety profile of etaracizumab warrants further exploration in ongoing phase I/II trials.
Delbaldo
Catherine
C
Department of Medical Oncology, Beaujon University Hospital, Clichy, France.
Raymond
Eric
E
Vera
Karina
K
Hammershaimb
Luz
L
Kaucic
Karen
K
Lozahic
Stéphanie
S
Marty
Michel
M
Faivre
Sandrine
S
D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000855:Anorexia / Q000139:chemically induced; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors* / Q000276:immunology; D007700:Kinetics; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D039302:Integrin alphaVbeta3; C112567:etaracizumab