A Phase I Study with the Bispecific Anti-CD30 × Anti-CD16A Antibody Construct AFM13 in Patients with Relapsed or Refractory Hodgkin Lymphoma,
Authors: Rothe Achim , Younes Anas , Reiners Katrin S. , Dietlein Markus , Eichenauer Dennis A. , Kessler Joerg , Topp Max S. , Hummel Horst , Ravic Miroslav , Hucke Christian , von Strandmann Elke Pogge , Engert Andreas 
Published: October 2019

Abstract
Abstract 3709

Background:
AFM13 is a bispecific, tetravalent human antibody construct (TandAb®) designed for the treatment of Hodgkin Lymphoma or other CD30-expressing malignancies. AFM13 specifically targets CD30, which is homogenously expressed on Hodgkin tumor cells and recruits NK cells as immune effector cells via the targeting of CD16A. Preclinical data demonstrate a specific and efficient anti-tumor activity delivering its therapeutic payload via the engagement of NK-cells.

Methods:
AFM13 is currently being evaluated in a single arm phase I dose escalation trial for patients with relapsed and/or refractory Hodgkin Lymphoma. The overall objective of this study is to evaluate safety, tolerability, pharmacokinetics, immunogenicity, antitumor activity, the maximum tolerated dose and the optimal biological dose of AFM13. Each patient receives a single cycle, consisting of one dose of AFM13 given once weekly for four weeks. The doses are escalated in cohorts of three patients at the dose levels of 0.01, 0.04, 0.15, 0.5, 1.5, 4.5 and 7.0 mg/kg. In responding patients, a second course of AFM13 can be considered. The safety of the maximum tolerated dose or the optimal biological dose will be confirmed in 12 additional patients.

Results:
So far, 15 patients with Hodgkin Lymphoma were enrolled and treated with doses of up to 0.5 mg/kg body weight. The median age was 37 years (range 20 to 57). 14/15 patients had received prior high dose chemotherapy and autologous stem cell transplantation with a median of 6 prior therapies (range 4 to 10). 8/15 patients were refractory to their most recent therapy. The study drug was well tolerated. Adverse events were generally mild, with the most frequent drug-related event being grade 1/2 fever occurring in 5/15 patients. One patient with known metastatic liver involvement developed a possibly drug-related dose-limiting grade 4 hemolytic anemia and a fatal, not drug-related suspected Aspergillus pneumonia. Of 10 evaluable patients who completed at least one cycle of therapy, 5 patients achieved stable disease, one of which showed a clear decrease in tumor volume. Biomarker analysis results show that the expression of the early activation marker CD69 on patient NK cells is significantly increased after treatment with AFM13. Moreover, in vitro cytotoxicity assays using patient NK cells demonstrate an effective killing of Hodgkin Lymphoma cells.

Conclusion:
This is the first clinical data on the bispecific, NK cell recruiting antibody construct AFM13 for the treatment of Hodgkin Lymphoma. AFM13 seems to be a new feasible and effective targeted therapy for heavily pre-treated patients with Hodgkin Lymphoma. Results of the ongoing phase I study will be presented.

Disclosures:
Younes: Genentech: Research Funding; Novartis: Honoraria, Research Funding; SBIO: Research Funding; Seattle Genetics: Honoraria, Research Funding; Syndax: Research Funding; Sanofi-Aventis: Honoraria, Research Funding. Topp:Micromet AG: Consultancy. Ravic:Affimed Therapeutics AG: Consultancy. Engert:Affimed Therapeutics AG: Honoraria, Research Funding.