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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., Middeke, J.M., Janz, M., Lenz, G., Witzens-Harig, M., Bouabdallah, R., La Rosée, P., Viardot, A., Salles, G., Kim, S.J., Kim, T.M., Ottmann, O., Chromik, J., Quinson, A.M., von Wangenheim, U., Burkard, U., 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 39(1): 283–284; Erratum in: Invest New Drugs 39(1): 285–286. |
| Official Publication: | https://doi.org/10.1007/s10637-020-00916-3 |
| PubMed: | View item in PubMed |
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