Phase IB trial for malignant melanoma using R24 monoclonal antibody, interleukin-2/alpha-interferon

The inflammatory tumor lymphocytic infiltrates and spontaneous tumor regres sions seen in patients with metastatic malignant melanomas suggest a cellul ar immune involvement. Enhancement of such responses has been the goal of R 24 (GD3 ganglioside-specific) monoclonal antibody trials, alone and in comb ination with other agents. This study reports the results of 21 patients tr eated in a phase IB trial employing R24 (0, 5, 25, 50 mg/m(2)) administered by continuous i.v. infusion on days 1-5 followed by 3 MU each of interleuk in-2 (IL-2) and alpha interferon (alpha-IFN) given subcutaneously on days 8 -12, 15-19 and 22-26. R24-related toxicities occurred pre-dominantly at the 25 and 50 mg/m(2) doses. One patient (50 mg/m(2) R24) exhibited a dose-lim iting Grade 4 anaphylaxis. Cytokine-related toxicities required IL-2/alpha- IFN dose reduction in two patients and early termination of treatment in fi ve additional patients. Nine of 20 baseline biopsies showed chronic inflamm ation; six with lymphocytic tumor infiltration and three where inflammation was confined to the perivascular/peritumoral spaces. No day 8 or 29 biopsi es in the R24-treated groups demonstrated treatment-induced tumor lymphocyt ic infiltrates. However, one patient randomized to no R24 treatment, showed a significant inflammatory tumor lymphocytic infiltration at days 8 and 29 . Eighteen of 21 treated patients were evaluable for response. One (5%) pat ient receiving IL-2/alpha-IFN alone had stable disease lasting 1.5 years. F ive (28%) R24, IL-2/alpha-IFN-treated patients had stable disease ranging f rom 6 to 32 weeks, with one patient remaining alive 2.5 years post-treatmen t. Although this combined treatment program was generally well tolerated, n o objective responses were seen and significant R24-induced tumor lymphocyt ic infiltrates were not demonstrated.