Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas

N Engl J Med. 2010 Nov 4;363(19):1812-21. doi: 10.1056/NEJMoa1002965.

Abstract

Background: Hodgkin's lymphoma and anaplastic large-cell lymphoma are the two most common tumors expressing CD30. Previous attempts to target the CD30 antigen with monoclonal-based therapies have shown minimal activity. To enhance the antitumor activity of CD30-directed therapy, the antitubulin agent monomethyl auristatin E (MMAE) was attached to a CD30-specific monoclonal antibody by an enzyme-cleavable linker, producing the antibody-drug conjugate brentuximab vedotin (SGN-35).

Methods: In this phase 1, open-label, multicenter dose-escalation study, we administered brentuximab vedotin (at a dose of 0.1 to 3.6 mg per kilogram of body weight) every 3 weeks to 45 patients with relapsed or refractory CD30-positive hematologic cancers, primarily Hodgkin's lymphoma and anaplastic large-cell lymphoma. Patients had received a median of three previous chemotherapy regimens (range, one to seven), and 73% had undergone autologous stem-cell transplantation.

Results: The maximum tolerated dose was 1.8 mg per kilogram, administered every 3 weeks. Objective responses, including 11 complete remissions, were observed in 17 patients. Of 12 patients who received the 1.8-mg-per-kilogram dose, 6 (50%) had an objective response. The median duration of response was at least 9.7 months. Tumor regression was observed in 36 of 42 patients who could be evaluated (86%). The most common adverse events were fatigue, pyrexia, diarrhea, nausea, neutropenia, and peripheral neuropathy.

Conclusions: Brentuximab vedotin induced durable objective responses and resulted in tumor regression for most patients with relapsed or refractory CD30-positive lymphomas in this phase 1 study. Treatment was associated primarily with grade 1 or 2 (mild-to-moderate) toxic effects. (Funded by Seattle Genetics; ClinicalTrials.gov number, NCT00430846.).

Publication types

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

MeSH terms

  • Adult
  • Aged, 80 and over
  • Brentuximab Vedotin
  • Chemokine CCL17 / blood
  • Dose-Response Relationship, Drug
  • Female
  • Hodgkin Disease / drug therapy*
  • Hodgkin Disease / immunology
  • Humans
  • Immunoconjugates / administration & dosage*
  • Immunoconjugates / adverse effects
  • Immunoconjugates / pharmacokinetics
  • Kaplan-Meier Estimate
  • Ki-1 Antigen
  • Lymphoma, Large-Cell, Anaplastic / drug therapy*
  • Lymphoma, Large-Cell, Anaplastic / immunology
  • Lymphoma, T-Cell / drug therapy*
  • Lymphoma, T-Cell / immunology
  • Male
  • Middle Aged
  • Peripheral Nervous System Diseases / chemically induced
  • Recurrence
  • Remission Induction
  • Young Adult

Substances

  • CCL17 protein, human
  • Chemokine CCL17
  • Immunoconjugates
  • Ki-1 Antigen
  • Brentuximab Vedotin

Associated data

  • ClinicalTrials.gov/NCT00430846