title: Phase I Study of Anti-GM2 Ganglioside Monoclonal Antibody BIW-8962 as Monotherapy in Patients with Previously Treated Multiple Myeloma.
abstract: BACKGROUND
  BIW-8962 is a monoclonal antibody to GM2 ganglioside that shows preclinical activity towards multiple myeloma (MM) cell lines and in animal models bearing MM xenografts. The objective of this study was to determine the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, potential immunogenicity, and preliminary clinical efficacy of BIW-8962 in patients with heavily pretreated MM.
  
  
  METHODS
  Patients (n= 23) received escalating doses of BIW-8962 (0.03-3 mg/kg) intravenously every 2 weeks in phase Ia. The highest anticipated dose (10 mg/kg) was not tested and the study was discontinued without proceeding to phases Ib and II.
  
  
  RESULTS
  The MTD of BIW-8962 was not established and BIW-8962 was relatively well tolerated. No pattern of consistent toxicity could be inferred from treatment-related AEs grade ≥3 and only two dose-limiting toxicities were recorded (atrial thrombosis + cardiomyopathy and chest pain, respectively). In the efficacy evaluable population (n= 22), no patient had a response (complete or partial) and 16 (72.7%) had a best response of stable disease, which was generally not durable.
  
  
  CONCLUSIONS
  BIW-8962 did not show evidence of clinical activity. The study was therefore stopped and further development of BIW-8962 in MM was halted.
  
  
  BACKGROUND
  This work was funded by Kyowa Kirin Pharmaceutical Development, Inc.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier, NCT00775502.
authors.affiliation: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL USA.
authors.forename: Rachid C
authors.initials: RC
authors.lastname: Baz
authors.affiliation: Department of Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Zonder
authors.affiliation: Duke Adult Blood and Marrow Transplant Clinic, Duke University Medical Center, Durham, NC USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gasparetto
authors.affiliation: Department of Hematology and Oncology, Cleveland Clinic Foundation, Cleveland, OH USA.
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: Reu
authors.affiliation: Kyowa Kirin Pharmaceutical Development, Inc., Princeton, NJ USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Strout
keywords: Anti-GM2 ganglioside monoclonal antibody; BIW-8962; Multiple myeloma; Phase I trial; Safety