Farletuzumab, a humanized monoclonal antibody against folate receptor alpha, in epithelial ovarian cancer: a phase I study.
OBJECTIVE
Folate receptor α expression is highly restricted in normal adult tissues but upregulated in a wide range of human cancer types, including epithelial ovarian cancer. Farletuzumab, a humanized monoclonal antibody against folate receptor α, has shown antitumor activity and favorable toxicity in preclinical evaluation. This phase I, dose-escalation study was conducted to determine the safety of weekly i.v. farletuzumab and establish the maximum tolerated dose (MTD).


METHODS
Patients with platinum-refractory or platinum-resistant epithelial ovarian cancer received farletuzumab (12.5-400 mg/m(2)) on days 1, 8, 15, and 22 of a 5-week cycle. Intrapatient dose escalation was not permitted. Dose-limiting toxicity (DLT) was defined by treatment-related adverse event of grade 3 or higher, and the MTD was the highest dose at which one or none of six patients experienced a DLT. Disease progression was recorded using Response Evaluation Criteria in Solid Tumors criteria and serum CA-125.


RESULTS
Twenty-five heavily pretreated patients were included in the safety, efficacy, and pharmacokinetic analyses. No DLTs or MTDs were encountered, and dose escalation was continued to farletuzumab 400 mg/m(2). C(max) and AUC(0-24) (area under the serum concentration-time curve) increased in an approximately dose-proportional manner, and a nuclear imaging substudy confirmed tumor targeting. There were no objective responses. Stable disease by Response Evaluation Criteria in Solid Tumors was observed in nine (36%) patients and CA-125 reduction in four. Three patients received continued therapy and completed a total of up to three cycles.


CONCLUSIONS
In this phase I study, farletuzumab administered as an i.v. infusion at doses of 12.5 to 400 mg/m(2) was generally safe and well tolerated in the management of heavily pretreated patients with epithelial ovarian cancer.
Konner
Jason A
JA
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. konnerj@mskcc.org
Bell-McGuinn
Katherine M
KM
Sabbatini
Paul
P
Hensley
Martee L
ML
Tew
William P
WP
Pandit-Taskar
Neeta
N
Vander Els
Nicholas
N
Phillips
Martin D
MD
Schweizer
Charles
C
Weil
Susan C
SC
Larson
Steven M
SM
Old
Lloyd J
LJ
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D058975:Folate Receptor 1 / Q000037:antagonists & inhibitors / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000628:therapy*; D017211:Treatment Failure; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D058975:Folate Receptor 1; C527484:farletuzumab; D002945:Cisplatin