A Phase 1b/2 trial of mapatumumab in patients with relapsed/refractory non-Hodgkin's lymphoma

Br J Cancer. 2010 Dec 7;103(12):1783-7. doi: 10.1038/sj.bjc.6605987. Epub 2010 Nov 16.

Abstract

Background: we conducted a multicentre Phase 1b/2 trial to evaluate the safety and efficacy of mapatumumab, a fully human agonistic monoclonal antibody to the tumour necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) in patients with relapsed non-Hodgkin's lymphoma (NHL).

Methods: forty patients with relapsed or refractory NHL were treated with either 3 or 10 mg kg(-1) mapatumumab every 21 days. In the absence of disease progression or prohibitive toxicity, patients received a maximum of six doses.

Results: mapatumumab was well tolerated, with no patients experiencing drug-related hepatic or other dose-limiting toxicity. Three patients with follicular lymphoma (FL) experienced clinical responses, including two with a complete response and one with a partial response. Immunohistochemistry staining of the TRAIL-R1 suggested that strong staining in tumour specimens did not appear to be a requirement for mapatumumab activity in FL.

Conclusions: mapatumumab is safe and has promising clinical activity in patients with FL.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Female
  • Humans
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Male
  • Middle Aged
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / analysis
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / antagonists & inhibitors*
  • Recurrence

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • mapatumumab