title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute and Clinical Center, NIH, Bethesda, Maryland 20892-4264, USA. hassanr@mail.nih.gov .
authors.forename: Raffit
authors.initials: R
authors.lastname: Hassan
authors.forename: Susie
authors.initials: S
authors.lastname: Bullock
authors.forename: Ahalya
authors.initials: A
authors.lastname: Premkumar
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kreitman
authors.forename: Hedy
authors.initials: H
authors.lastname: Kindler
authors.forename: Mark C
authors.initials: MC
authors.lastname: Willingham
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage*; D007275:Injections, Intravenous; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*