PHASE I TRIAL OF I. P. OVB3-PE IN OVARIAN CANCER PATIENTS

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OVB3-PE is an immunoconjugate comprised of a IgG2b murine monoclonal antibody that recognizes an antigen on the surface of all human ovarian cancers and pseudomonas exotoxin joined by means of a thioether bond. Pseudomonas exotoxin is a bacterial toxin that kills cells by inhibiting protein synthesis. This immunotoxin was shown to kill human ovarian cancer cells in vitro. Studies of this immunotoxin in mice with the OVCAR 3 ascites tumor demonstrated that mice receiving the immunotoxin had a significantly prolonged survival. We conducted a Phase I study of the OVB3-PE immunotoxin given as multiple intraperitoneal infusions in patients with refractory ovarian carcinoma involving the peritoneal cavity in order to determine the toxicity of treatment, to determine serum and intraperitoneal levels of OVB3-PE, to determine the types of host anti-- immunotoxin antibodies that might develop, and to assess any antitumor activity of the immunotoxin. Seventeen patients were entered onto this nonrandomized, Phase I multi-dose escalation study. Patients were entered from several different cooperating institutions. The BRMP entered 3 patients - one at the 2 mcg/kg dose level and 2 at the 10 mcg/kg dose level. One of our 3 patients sustained grade 3 pain and neurological toxicity after treatment with 10 mcg/kg. Similar but not identical grade 3 neurological toxicity was also observed in another patient treated at the Medicine Branch, NCI and as a result, no further dose escalations occurred beyond 10 mcg/kg. Despite intensive investigation, the mechanism for the neurotoxicity in these patients has not been elucidated. The protocol- has been amended to treat 4 more groups of patients all at 5 mcg/k-g b-ut with the number of doses increasing from 3 to 8, all administered within 12 days. Patients will begin treatment on the revised schedule starting in July 1989.