PHASE-I STUDY OF R24 IN PATIENTS WITH METASTATIC MELANOMA INCLUDING EVALUATION OF IMMUNOLOGICAL PARAMETERS

R24 is a mouse I(g)G3 monoclonal antibody with specificity for the dis ialoganglioside GD3. Most human melanomas have substantial surface GD3 ; in addition, a significant proportion of T lymphocytes display surfa ce GD3. In a phase I study, we have investigated the toxicity and effe ct on selected immunological parameters of three dose levels of R24 gi ven intravenously daily for five days (10 mg/m(2)/d, 30 mg/m(2)/d and 50 mg/m(2)/d) to patients with advanced melanoma. R24 administration n either consistently diminished nor augmented expression of delayed typ e hypersensitivity (DTH) skin reactions to anergy panel antigens or to a contact allergen dinitrofluorobenzene. R24 was infrequently found o n tumor cells, or on lymphocytes from DTH biopsies, despite measurable serum levels of R24. The 30 mg/m(2)/d dose of R24 produced a statisti cally significant drop in peripheral blood lymphocytes on treatment Da y 5. Likewise, on Day 5 there was a modest but statistically significa nt decrement in the proportion of circulating cells which were R24+. W hile there was one mixed response, there were no complete or partial t umor regressions in the R24 treated patients; there was no evident cli nical benefit from the R24 therapy. The toxicity of the R24 at the hig her dose levels can be very substantial. One patient, on the highest d ose level, died on the 4th day of R24 treatment, in the absence of a p lausible alternative explanation, a relationship of the death to the a dministered R24 must be considered. A precipitous drop in serum albumi n coincident with R24 administration was found in all cases; this effe ct has not been previously reported with R24.