PHASE-I CLINICAL-TRIAL IN CANCER-PATIENTS OF A NEW MONOCLONAL-ANTIBODY FC-2.15 REACTING WITH TUMOR PROLIFERATING CELLS

FC-2.15 is a new murine IgM monoclonal antibody (MAb) that recognizes previously undescribed antigens present in proliferating breast cancer cells and normal peripheral granulocytes. A phase I clinical trial was performed in 11 patients with advanced cancer (breast, 5; colon, 2; melanoma, 1; lung, 1; medullary thyroid, 1; skin squamous carcinoma, 1). FC-2.15 was administered by i.v. infusion every other day; eight patients received four infusions, two patients three infusions and one patient received two infusions. One patient received two cycles of treatment. Total doses of MAb ranged between 2.5 and 5 mg/kg. Maximal FC-2.15 serum concentrations for different patients ranged between 1.3 and 7.5 mu g/ml, and the serum half-life (t(1/2)-alpha) was similar to 7-9 h. All patients developed human anti-murine antibody. The most consistent toxicity (10 of 11 patients) was a profound and selective neutropenia that occurred within 1 h after the start of each infusion and reversed within 1 h after its discontinuation. Other frequent side effects included fever and chills that were easily manageable. Only two patients needed dose reduction or treatment interruption. The patient who received two treatment cycles did not develop allergic reactions. An objective partial response, consisting of a sustained (4 months) >50% reduction of breast carcinoma liver metastases, was observed.