Phase I dose escalation study of BI 836826 (CD37 antibody) in patients with relapsed or refractory B-cell non-Hodgkin lymphoma


  • F. Kroschinsky
  • J.M. Middeke
  • M. Janz
  • G. Lenz
  • M. Witzens-Harig
  • R. Bouabdallah
  • P. La Rosée
  • A. Viardot
  • G. Salles
  • S.J. Kim
  • T.M. Kim
  • O. Ottmann
  • J. Chromik
  • A.M. Quinson
  • U. von Wangenheim
  • U. Burkard
  • A. Berk
  • N. Schmitz


  • Investigational New Drugs


  • Invest New Drugs 38 (5): 1472-1482


  • BI 836826 is a chimeric immunoglobulin G1 antibody targeting CD37, a tetraspanin transmembrane protein predominantly expressed on normal and malignant B cells. This phase I, open-label study used a modified 3 + 3 design to evaluate the safety, maximum tolerated dose (MTD), pharmacokinetics, and preliminary activity of BI 836826 in patients with relapsed/refractory B cell non-Hodgkin lymphoma (NHL; NCT01403948). Eligible patients received up to three courses comprising an intravenous infusion (starting dose: 1 mg) once weekly for 4 weeks followed by an observation period of 27 (Course 1, 2) or 55 days (Course 3). Patients had to demonstrate clinical benefit before commencing treatment beyond course 2. Forty-eight patients were treated. In the dose escalation phase (1-200 mg) involving 37 Caucasian patients, the MTD was 100 mg. Dose-limiting toxicities occurred in four patients during the MTD evaluation period, and included stomatitis, febrile neutropenia, hypocalcemia, hypokalemia, and hypophosphatemia. The most common adverse events were neutropenia (57%), leukopenia (57%), and thrombocytopenia (41%), and were commonly of grade 3 or 4. Overall, 18 (38%) patients experienced infusion-related reactions, which were mostly grade 1 or 2. Preliminary evidence of anti-tumor activity was seen; three patients responded to treatment, including one complete remission in a Korean patient with diffuse large B cell lymphoma. BI 836826 plasma exposure increased more than proportionally with increasing doses. BI 836826 demonstrated preliminary activity; the most frequent adverse events were hematotoxicity and infusion-related reactions which were manageable after amending the infusion schedule. Although BI 856826 will not undergo further clinical development, these results confirm CD37 as a valid therapeutic target in B cell NHL.