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@article{2292839,
author = {Topp, Max and DlugoszandDanecka, Monika and Skotnicki, Aleksander B and Salogub, Galina and Viardot, Andreas and Klein, Andreas K and Hess, Georg and Michel, Christian S and Grosicki, Sebastian and Gural, Alex and Schwarz, Sylvia E and Pietzko, Kerstin and Gaertner, Ulrike and Strassz, Andras and Alland, Leila and Mayer, Jiří},
article_location = {LONDON},
article_number = {1},
doi = {http://dx.doi.org/10.1186/s13063-022-06982-7},
keywords = {Non-Hodgkin lymphoma; Acute lymphoblastic leukaemia; AFM11; Neurotoxicity; T-cell engager},
language = {eng},
issn = {1745-6215},
journal = {Trials},
title = {Safety of AFM11 in the treatment of patients with B-cell malignancies: findings from two phase 1 studies},
url = {https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-022-06982-7},
volume = {24},
year = {2023}
}
TY - JOUR
ID - 2292839
AU - Topp, Max - Dlugosz-Danecka, Monika - Skotnicki, Aleksander B - Salogub, Galina - Viardot, Andreas - Klein, Andreas K - Hess, Georg - Michel, Christian S - Grosicki, Sebastian - Gural, Alex - Schwarz, Sylvia E - Pietzko, Kerstin - Gaertner, Ulrike - Strassz, Andras - Alland, Leila - Mayer, Jiří
PY - 2023
TI - Safety of AFM11 in the treatment of patients with B-cell malignancies: findings from two phase 1 studies
JF - Trials
VL - 24
IS - 1
SP - 1-11
EP - 1-11
PB - BMC
SN - 17456215
KW - Non-Hodgkin lymphoma
KW - Acute lymphoblastic leukaemia
KW - AFM11
KW - Neurotoxicity
KW - T-cell engager
UR - https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-022-06982-7
N2 - Background: The prognosis for patients with relapsed and/or refractory (R/R) non-Hodgkin's lymphoma (NHL) or acute lymphoblastic leukaemia (ALL) remains poor, with existing treatments having significant side effects. Developed for the treatment of these cancers, AFM11 is a tetravalent, bispecific humanised recombinant antibody construct (TandAb (R)) designed to bind to human CD19 and CD3 and lead to the activation of T cells inducing apoptosis and killing of malignant B cells.Methods: Two open-label, multicentre, dose-escalation phase 1 studies evaluated the safety, pharmacokinetics and activity of AFM11 in patients with R/R CD19-positive B cell NHL (AFM11-101) and in patients with CD19 + B-precursor Philadelphia-chromosome negative ALL (AFM11-102). Adverse events (AEs) were assessed and recorded; imaging (NHL) or bone marrow assessment (ALL) were used to evaluate response. Additional pharmacodynamic assays undertaken included cytokine release analysis and B-cell and T-cell depletion.Results: In AFM11-101, 16 patients with R/R NHL received AFM11 in five different dose cohorts. Of which, 14 experienced drug-related treatment-emergent AEs (TEAEs) [including five serious AEs (SAEs)], five patients experienced dose-limiting toxicity (DLT) and ten patients discontinued the study. The high number of neurological events led to a decrease in infusion frequency during the study. No objective response to treatment was observed. In AFM11-102, 17 patients with R/R ALL received AFM11 in six different dose cohorts. Thirteen patients experienced drug-related TEAEs (including four SAEs), DLTs occurred in two patients and five patients discontinued the study. An objective response was recorded in three patients. The maximum tolerated dose could not be determined in either study due to early termination.Conclusions: AFM11 treatment was associated with frequent neurological adverse reactions that were severe in some patients. In ALL, some signs of activity, albeit short-lived, were observed whereas no activity was observed in patients with NHL; therefore, further clinical development was terminated
ER -
TOPP, Max, Monika DLUGOSZ-DANECKA, Aleksander B SKOTNICKI, Galina SALOGUB, Andreas VIARDOT, Andreas K KLEIN, Georg HESS, Christian S MICHEL, Sebastian GROSICKI, Alex GURAL, Sylvia E SCHWARZ, Kerstin PIETZKO, Ulrike GAERTNER, Andras STRASSZ, Leila ALLAND and Jiří MAYER. Safety of AFM11 in the treatment of patients with B-cell malignancies: findings from two phase 1 studies. \textit{Trials}. LONDON: BMC, 2023, vol.~24, No~1, p.~1-11. ISSN~1745-6215. Available from: https://dx.doi.org/10.1186/s13063-022-06982-7.
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