Farletuzumab, a humanized monoclonal antibody against folate receptor α, in epithelial ovarian cancer: A phase I study Journal Article

Authors: Konner, J. A.; Bell-Mcguinn, K. M.; Sabbatini, P.; Hensley, M. L.; Tew, W. P.; Pandit-Taskar, N.; Vander Els, N.; Phillips, M. D.; Schweizer, C.; Weil, S. C.; Larson, S. M.; Old, L. J.
Article Title: Farletuzumab, a humanized monoclonal antibody against folate receptor α, in epithelial ovarian cancer: A phase I study
Abstract: Purpose: 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). Experimental Design: Patients with platinum-refractory or platinum-resistant epithelial ovarian cancer received farletuzumab (12.5-400 mg/m2) 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/m2. Cmax and AUC0-24 (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/m2 was generally safe and well tolerated in the management of heavily pretreated patients with epithelial ovarian cancer. ©2010 AACR.
Keywords: adult; clinical article; controlled study; treatment outcome; aged; middle aged; treatment failure; unclassified drug; clinical trial; fatigue; cisplatin; doxorubicin; area under the curve; diarrhea; drug efficacy; drug safety; antineoplastic agents; gemcitabine; topotecan; neurotoxicity; ovarian neoplasms; controlled clinical trial; multiple cycle treatment; ovary cancer; antineoplastic activity; dose-response relationship, drug; drug resistance, neoplasm; monoclonal antibody; chill; coughing; drug dose escalation; drug fever; drug hypersensitivity; dyspnea; pruritus; antibodies, monoclonal; immunotherapy; drug distribution; acne; headache; drug blood level; maximum tolerated dose; phase 1 clinical trial; ca 125 antigen; navelbine; drug dose regimen; folate receptor alpha; neoplasms, glandular and epithelial; farletuzumab; folate receptor; morab 003; epithelial ovary cancer; folate receptor 1
Journal Title: Clinical Cancer Research
Volume: 16
Issue: 21
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2010-11-01
Start Page: 5288
End Page: 5295
Language: English
DOI: 10.1158/1078-0432.ccr-10-0700
PUBMED: 20855460
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 3" - "Export Date: 20 April 2011" - "CODEN: CCREF" - "Source: Scopus"
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MSK Authors
  1. Jason Konner
    84 Konner
  2. Paul J Sabbatini
    199 Sabbatini
  3. Martee L Hensley
    220 Hensley
  4. William P Tew
    122 Tew
  5. Steven M Larson
    762 Larson