Phase I study of U3-1287, a fully human anti-HER3 monoclonal antibody, in patients with advanced solid tumors Journal Article

Authors: LoRusso, P.; Jänne, P. A.; Oliveira, M.; Rizvi, N.; Malburg, L.; Keedy, V.; Yee, L.; Copigneaux, C.; Hettmann, T.; Wu, C. Y.; Ang, A.; Halim, A. B.; Beckman, R. A.; Beaupre, D.; Berlin, J.
Article Title: Phase I study of U3-1287, a fully human anti-HER3 monoclonal antibody, in patients with advanced solid tumors
Abstract: Purpose: HER3 is a key dimerization partner for other HER family members, and its expression is associated with poor prognosis. This first-in-human study of U3-1287 (NCT00730470), a fully human anti-HER3 monoclonal antibody, evaluated its safety, tolerability, and pharmacokinetics in patients with advanced solid tumor. Experimental Design: The study was conducted in 2 parts: part 1 - sequential cohorts received escalating doses (0.3-20 mg/kg) of U3-1287 every 2 weeks, starting 3 weeks after the first dose; part 2 - additional patients received 9, 14, or 20 mg/kg U3-1287 every 2 weeks, based on observed tolerability and pharmacokinetics from part 1. Recommended phase II dose, adverse event rates, pharmacokinetics, and tumor response were determined. Results: Fifty-seven patients (part 1: 26; part 2: 31) received U3-1287. As no dose-limiting toxicities were reported, the maximum-tolerated dose was not reached. The maximum-administered dose was 20 mg/kg every 2 weeks. The most frequent adverse events related to U3-1287 were fatigue (21.1%), diarrhea (12.3%), nausea (10.5%), decreased appetite (7.0%), and dysgeusia (5.3%). No patient developed anti-U3-1287 antibodies. In these heavily pretreated patients, stable disease was maintained 9 weeks or more in 19.2% in part 1 and 10 weeks or more in 25.8% in part 2. Conclusion: U3-1287 treatment was well tolerated, and some evidence of disease stabilization was observed. Pharmacokinetic data support U3-1287 dosing of 9 to 20 mg/kg every 2 to 3 weeks. Combination studies of U3-1287 are ongoing. ©2013 AACR.
Journal Title: Clinical Cancer Research
Volume: 19
Issue: 11
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2013-06-01
Start Page: 3078
End Page: 3087
Language: English
DOI: 10.1158/1078-0432.ccr-12-3051
PROVIDER: scopus
PUBMED: 23591447
Notes: --- - "Export Date: 1 July 2013" - "CODEN: CCREF" - "Source: Scopus"
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MSK Authors
  1. Naiyer A Rizvi
    166 Rizvi