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

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Item Type:Article
Title:Phase I dose escalation study of BI 836826 (CD37 antibody) in patients with relapsed or refractory B-cell non-Hodgkin lymphoma
Creators Name:Kroschinsky, F. and Middeke, J.M. and Janz, M. and Lenz, G. and Witzens-Harig, M. and Bouabdallah, R. and La Rosée, P. and Viardot, A. and Salles, G. and Kim, S.J. and Kim, T.M. and Ottmann, O. and Chromik, J. and Quinson, A.M. and von Wangenheim, U. and Burkard, U. and Berk, A. and Schmitz, N.
Abstract: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.
Keywords:BI 836826, CD37, Diffuse Large B Cell Lymphoma, Non-Hodgkin Lymphoma, Phase I, Relapsed
Source:Investigational New Drugs
ISSN:0167-6997
Publisher:Springer
Volume:38
Number:5
Page Range:1472-1482
Date:October 2020
Additional Information:Erratum in: Invest New Drugs. 2020 May 31 [in Press]; Erratum in: Invest New Drugs. 2020 Jun 23 [in Press]
Official Publication:https://doi.org/10.1007/s10637-020-00916-3
PubMed:View item in PubMed

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