title: A Phase II Study of PF-03446962 in Patients with Advanced Malignant Pleural Mesothelioma. CCTG Trial IND.207.
abstract: There is no approved second-line systemic therapy option for malignant pleural mesothelioma (MPM), but targeting angiogenesis is an area of investigation. PF-03446962 is a fully human antibody against activin receptor-like kinase 1, which is commonly expressed in tumor vasculature. We performed a multicenter, open label, single-arm, two-stage phase II study of PF-03446962 in patients with MPM and progressive disease after platinum-based chemotherapy. In total, 17 patients were enrolled, but no partial or complete responses were observed. The trial did not meet the prespecified response criterion for moving to the second stage. There were only three grade 3 (G3) or higher nonhematological toxicities observed (G3 hypertension [n=2] and G3 fatigue [n=1]) and just one episode of G3 lymphopenia. In conclusion, PF-03446962, despite being generally well tolerated, failed to demonstrate efficacy in the treatment of advanced MPM as a single agent. There are no plans for further investigation of this agent in MPM.
authors.affiliation: Ottawa Hospital Cancer Centre/Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. Electronic address: pwheatleyprice@toh.on.ca.
authors.forename: Paul
authors.initials: P
authors.lastname: Wheatley-Price
authors.affiliation: Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: Quincy
authors.initials: Q
authors.lastname: Chu
authors.affiliation: Canadian Cancer Trials Group, Queen's University, Ontario, Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Bonomi
authors.affiliation: Ottawa Hospital Cancer Centre/Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Seely
authors.affiliation: Ottawa Hospital Cancer Centre/Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Ashish
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Ottawa Hospital Cancer Centre/Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Glenwood
authors.initials: G
authors.lastname: Goss
authors.affiliation: Canadian Cancer Trials Group, Queen's University, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Hilton
authors.affiliation: Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Ronald
authors.initials: R
authors.lastname: Feld
authors.affiliation: British Columbia Cancer Agency-Fraser Valley Centre, Surrey, British Columbia, Canada.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, Ontario, Canada.
authors.forename: John R
authors.initials: JR
authors.lastname: Goffin
authors.affiliation: CancerCare Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Maksymiuk
authors.affiliation: British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia, Canada.
authors.forename: Nevin
authors.initials: N
authors.lastname: Murray
authors.affiliation: Canadian Cancer Trials Group, Queen's University, Ontario, Canada.
authors.forename: Linda
authors.initials: L
authors.lastname: Hagerman
authors.affiliation: Canadian Cancer Trials Group, Queen's University, Ontario, Canada.
authors.forename: Penelope A
authors.initials: PA
authors.lastname: Bradbury
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C575087:ascrinvacumab
keywords: ALK-1 antagonist; Angiogenesis; Malignant pleural mesothelioma; Systemic therapy