Phase I study of SS1P, a recombinant anti-mesothelin immunotoxin given as a bolus I.V. infusion to patients with mesothelin-expressing mesothelioma, ovarian, and pancreatic cancers.

PURPOSE: To determine the toxicities, maximum tolerated dose (MTD) and pharmacokinetics of the recombinant immunotoxin SS1P (anti-mesothelin dsFv-PE38) in patients with mesothelin-expressing cancers. EXPERIMENTAL DESIGN: SS1P given as a 30-min i.v. infusion every other day (QOD) for six or three doses was administered to 34 patients with advanced mesothelioma (n = 20), ovarian (n = 12), and pancreatic (n = 2) cancer. RESULTS: The initial cohort of 17 patients received SS1P QOD x 6 doses and the MTD was 18 microg/kg/dose. Dose-limiting toxicities (DLT) included grade 3 uticaria (one patient) and grade 3 vascular leak syndrome (two patients). To allow further SS1P dose escalation, 17 patients were treated on the QOD x 3 schedule and the MTD was 45 microg/kg/dose. The DLT was grade 3 pleuritis and was seen in two of two patients treated at a dose of 60 microg/kg and in one of nine patients treated at a dose of 45 microg/kg. At the MTD of 45 microg/kg, the mean C(max) of SS1P was 483 ng/mL and half-life was 466 min. Of the 33 evaluable patients treated, 4 had minor responses, 19 had stable disease (including 2 with resolution of ascites), and 10 had progressive disease. CONCLUSIONS: SS1P is well tolerated with pleuritis as the DLT at the highest dose level. Evidence of clinical activity was noted in a group of heavily pretreated patients. Phase II clinical trials of SS1P are being planned for malignant mesothelioma and other mesothelin-expressing malignancies.