Phase I dose escalation study of BI 836826 (CD37 antibody) in patients with relapsed or refractory B-cell non-Hodgkin ly
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PHASE I STUDIES
Phase I dose escalation study of BI 836826 (CD37 antibody) in patients with relapsed or refractory B-cell non-Hodgkin lymphoma Frank Kroschinsky 1 & Jan Moritz Middeke 1 & Martin Janz 2 & Georg Lenz 3 & Mathias Witzens-Harig 4 & Reda Bouabdallah 5 & Paul La Rosée 6,7 & Andreas Viardot 8 & Gilles Salles 9 & Seok Jin Kim 10 & Tae Min Kim 11,12 & Oliver Ottmann 13 & Joerg Chromik 14 & Anne-Marie Quinson 15 & Ute von Wangenheim 16 & Ute Burkard 16 & Andreas Berk 17 & Norbert Schmitz 3 Received: 21 November 2019 / Accepted: 24 February 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Summary 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
Introduction Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of malignant disorders with variable clinical and biologic features that together caused over 248,000 deaths worldwide in 2018 [1, 2]. Most NHLs are of B cell origin, and the most common form, diffuse large B cell lymphoma (DLBCL), is an a g g r e s s i v e s u b ty p e t h a t i s r e a d i ly c u r a b l e w i t h Electronic supplementary material The online version of this article (https://doi.org/10.1007/s106
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