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Clinical Trial
. 2023 Jan 3;24(1):4.
doi: 10.1186/s13063-022-06982-7.

Safety of AFM11 in the treatment of patients with B-cell malignancies: findings from two phase 1 studies

Max Topp  1 , Monika Dlugosz-Danecka  2 , Aleksander B Skotnicki  3 , Galina Salogub  4 , Andreas Viardot  5 , Andreas K Klein  6 , Georg Hess  7 , Christian S Michel  7 , Sebastian Grosicki  8 , Alex Gural  9 , Sylvia E Schwarz  10 , Kerstin Pietzko  10 , Ulrike Gärtner  11 , András Strassz  10 , Leila Alland  10 , Jiri Mayer  12
Affiliations
Clinical Trial

Safety of AFM11 in the treatment of patients with B-cell malignancies: findings from two phase 1 studies

Max Topp et al. Trials. .

Abstract

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®) 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.

Trial registration: NCT02106091 . Safety Study to Assess AFM11 in Patients With Relapsed and/or Refractory CD19 Positive B-cell NHL. Registered April 2014. NCT02848911 . Safety Study to Assess AFM11 in Patients With Relapsed or Refractory Adult B-precursor ALL. Registered July 2016.

Keywords: AFM11; Acute lymphoblastic leukaemia; Neurotoxicity; Non-Hodgkin lymphoma; T-cell engager.

PubMed Disclaimer

Conflict of interest statement

SES, KP and UG are employees of Affimed GmbH. AS and LA were employees of Affimed GmbH at the time of the study.

Figures

Fig. 1
Fig. 1
CONSORT flow diagram. Dose of AFM11 by cohort (cycle 1 week 1, cycle 1 week 2 onward) was as follows: cohort 1, 0.0007 μg/kg/week, 0.002 μg/kg/week; cohort 2, 0.002 μg/kg/week, 0.006 μg/kg/week; cohort 3, 0.007 μg/kg/week, 0.02 μg/kg/week; cohort 4, 0.02 μg/kg/week, 0.06 μg/kg/week; cohort 5, 0.06 μg/kg/week, 0.18 μg/kg/week; cohort 6, 0.13 μg/kg/week, 0.4 μg/kg/week
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