PHASE IB TRIAL OF CHIMERIC ANTIDISIALOGANGLIOSIDE ANTIBODY PLUS INTERLEUKIN-2 FOR MELANOMA PATIENTS

We conducted a Phase IB trial of antidisialoganglioside chimeric 14.18 (ch14.18) antibody and interleukin 2 (IL-2) to determine the maximal tolerated dose (MTD), immunological effects, antitumor effects, and to xicity of this treatment combination, Twenty-four melanoma patients re ceived immunotherapy with ch14.18 antibody and a continuous infusion o f Roche IL-2 (1.5 x 10(6) units/m(2)/day) given 4 days/week for 3 week s, The ch14.18 antibody (dose level, 2-10 mg/m(2)/day) was scheduled t o be given for 5 days, before, during, or following initial systemic I L-2 treatment, The ch14.18 MTD was 7.5 mg/m(2)/day, and 15 patients we re treated with the ch14.18 MTD, Immunological effects included the in duction of lymphokine-activated killer activity and antibody dependent cellular cytotoxicity by peripheral blood mononuclear cells, In addit ion, serum samples obtained following ch14.18 infusions were able to f acilitate in vitro antibody-dependent cellular cytotoxicity. Antitumor activity included one complete response, one partial response, eight patients with stable disease, and one patient with >50% decrease of he patic metastases in the face of recurrence of a s.c. lesion, Dose-limi ting toxicities were a severe allergic reaction and weakness, pericard ial effusion, and decreased performance status, Most patients treated at the MTD had abdominal, chest, or extremity pain requiring i.v. morp hine, One patient had an objective peripheral neuropathy, This IL-2 an d ch14.18 treatment combination induces immune activation in all patie nts and antitumor activity in some melanoma patients, We are attemptin g to enhance this treatment approach by addition of the anti-GD3 R24 a ntibody to this IL-2 and ch14.18 regimen.