Phase I pilot clinical trial of human IgM monoclonal antibody to ganglioside GM3 in patients with metastatic melanoma.

PURPOSE

A human monoclonal antibody (L612 HuMAb) that binds to ganglioside GM3 has been developed in our laboratory. L612 HuMAb is a 100% human IgM protein. L612 HuMAb binds to cell surface of melanoma and can kill the cells in the presence of complement. The primary objective of this study was to test the toxicity and pharmacokinetics associated with administration of L612 HuMAb to melanoma patients whose tumor cells expressed GM3.

EXPERIMENTAL DESIGN

Nine patients with measurable metastatic melanoma (American Joint Committee on Cancer stage IV) were entered in the study. Eight had failed previous treatments that included chemotherapy, radiation therapy, melanoma cell vaccine, and/or biological therapy. All patients received a 48-h continuous infusion of L612 HuMAb at a dose of 960 mg, 1,440 mg, or 1,920 mg. Five of these patients received a second infusion and one patient received a third infusion, all with the previous dose.

RESULTS

Toxicity was limited to transient and mild pruritus and skin rash. One patient complained of pain at the site of subcutaneous metastases. Serum antibody levels peaked 24 to 48 h after starting the infusion. Two patients, one receiving a single course of 960 mg (612 mg/m(2)) and the second receiving two courses of 1,440 mg (911 mg/m(2)) followed by surgical therapy, are without evidence of disease >5 years after antibody infusion.

CONCLUSIONS

The human IgM monoclonal antibody, L612 HuMAb, was well tolerated. Infusion of L612 HuMAb appears to produce significant antitumor activity in melanoma patients.