Originally published as JCO Early Release 10.1200/JCO.2004.11.061 on June 21 2004

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Safety, Pharmacokinetics, and Activity of ABX-EGF, a Fully Human Anti–Epidermal Growth Factor Receptor Monoclonal Antibody in Patients With Metastatic Renal Cell Cancer

From the Institute for Drug Development, Cancer Therapy and Research Center and Brook Army Medical Center, San Antonio, TX; Beth Israel Deaconess Cancer Center, Boston, MA; University of Washington, Seattle, WA; University of Chicago Cancer Research Center, Chicago, IL; Cleveland Clinic, Cleveland, OH; Fox Chase Cancer Center, Philadelphia, PA; UCLA School of Medicine, Los Angeles; and Abgenix Inc, Fremont, CA; and Our Lady of Mercy Cancer Center, New York. Medical College, Bronx, NY

Address reprint requests to Eric K. Rowinsky, MD, Institute for Drug Development, Cancer Therapy and Research Center, 7979 Wurzbach Rd, 4th Floor, Zeller Building, San Antonio, TX 78229; e-mail: erowinsk{at}idd.org

PURPOSE: To determine the antitumor activity of ABX-EGF, a fully human monoclonal antibody to the epidermal growth factor receptor (EGFr), in previously treated patients with metastatic renal cell carcinoma, and to characterize its toxicity, immunogenicity, pharmacokinetics, and pharmacodynamics.

PATIENTS AND METHODS: The antitumor activity, as well as the toxicity, pharmacokinetics, pharmacodynamics, and immunogenicity of ABX-EGF, were assessed.

RESULTS: Eighty-eight patients were treated with ABX-EGF doses of 1.0, 1.5, 2.0, or 2.5 mg/kg weekly with no loading dose. EGFr immunostaining was performed on 76 tumor biopsy specimens (86%), and 69 (91%) scored positive. Major responses occurred in three patients, and two patients had minor responses. Forty-four patients (50%) also had stable disease at their first 8-week assessment, and the median progression-free survival (PFS) was 100 days (95% CI, 58 to 140 days). Low hemoglobin and high alkaline phosphatase predicted for short PFS. The principal toxicity, an acneiform rash, occurred in 68%, 95%, 87%, and 100% of patients who received at least three doses of ABX-EGF at 1.0, 1.5, 2.0, and 2.5 mg/kg/wk, respectively. A trend indicated that the severity of the rash may relate to PFS. No human antihuman antibodies were detected. ABX-EGF pharmacokinetics fit a model that incorporated both linear and saturable EGFr-mediated clearance mechanisms, and interindividual variability was low. At 2.5 mg/kg/wk, ABX-EGF concentrations throughout treatment exceeded those estimated to saturate nonlinear clearance and inhibit xenograft growth by 90%.

CONCLUSION: ABX-EGF was generally well tolerated. The objective response rate was low in previously treated patients with metastatic renal cell carcinoma. Although skin rash may be a pharmacodynamic marker of drug action, its potential as a surrogate marker of clinical benefit requires further evaluation.

Presented in part at the 38th annual meeting of the American Society of Clinical Oncology, Orlando, FL, May 18-21, 2002.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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