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Phase I Trial of the Murine Monoclonal Anti-G_D2 Antibody 14G2a in Metastatic Melanoma¹

Division of Hematology/Oncology and the Comprehensive Cancer Center [M. N. S., M. B. K., R. H. W., T. L., D. M. M., S. L., A. F. L.] and Department of Nuclear Medicine [C. H. R.], Surgical Oncology [M. U., P. D.], and Neurology [E. D.], University of Alabama at Birmingham, Birmingham, Alabama 35294-3300

In a phase I trial, 12 patients with G_D2 antigen-positive metastatic melanoma received the murine anti-G_D2 monoclonal antibody 14G2a. The monoclonal antibody was administered in four doses over an 8-day period with total dose ranging from 10 to 120 mg. All patients receiving >10 mg of 14G2a experienced transient abdominal/pelvic pain during the antibody infusion. Five patients had a delayed extremity pain syndrome following the third and fourth antibody infusion. Four of the five patients developed neurological toxicity, including two patients with significant although reversible motor neuropathy. Two of the patients developed hyponatremia secondary to a syndrome of inappropriate antidiuretic hormone. All 12 patients developed high levels of human anti-14G2a antibody. The plasma half-life of 14G2a was 42 ± 6 (SD) h. One patient each had a partial response, mixed response, and stable disease, respectively. The very modest antitumor activity accompanied by dose-limiting neurological toxicity at total doses >80 mg may restrict the clinical utility of murine 14G2a.

¹ This work was supported by Grant N01 CM-97611 of the National Cancer Institute.

² To whom requests for reprints should be addressed, at University of Alabama at Birmingham, Comprehensive Cancer Center, L. B. Wallace Tumor Institute—263, Birmingham, AL 35294-3300.

Received 8/ 5/91. Accepted 6/ 3/92.

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