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 wa s 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 pa tients received four infusions, two patients three infusions and one p atient received two infusions. One patient received two cycles of trea tment. 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 consi stent toxicity (10 of 11 patients) was a profound and selective neutro penia that occurred within 1 h after the start of each infusion and re versed within 1 h after its discontinuation. Other frequent side effec ts included fever and chills that were easily manageable. Only two pat ients 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.