1072P - Recruit-Tandab AFM13 - Overcoming Limitations of Monoclonal Antibodies in Hodgkin Lymphoma

Abstract

ABSTRACT AFM13 is a RECRUIT-TandAb (CD30xCD16A) for treating Hodgkin Lymphoma by recruiting NK-cells and macrophages to the specific CD30 surface antigen on Reed-Sternberg cells. This redirected immune response leads to potent tumor cell killing. RECRUIT TandAbs are tetravalent and bispecific, and address key deficiencies of monoclonal antibodies such as (i) differential binding to V/F allotypes of CD16A receptor and (ii) non-selective binding to activating CD16A and non-signalling CD16B receptors. Furthermore, RECRUIT-TandAbs have significant advantages over other antibody fragment technologies such as (i) bivalent binding to the targets and, (ii) longer half-life. AFM13 binds with high affinity to both CD30 and CD16A and is able to rapidly induce lysis of CD30+ cells at picomolar concentrations in the presence of PBMCs. Intensive in vitro characterization demonstrated that AFM13 is specific for the CD16A receptor, which becomes activated only in the presence of tumor cells: there is no systemic activation of NK-cells in the absence of target cells. A robust GMP production process in mammalian cells and a lyophilized formulation with excellent stability have been established. Toxicology testing in Cynomolgus monkeys did not reveal any toxicity. Currently, AFM13 is being investigated in a single arm phase I dose escalation trial for patients with relapsed and/or refractory Hodgkin Lymphoma (HL). Patients receive a single cycle of 4 weekly doses, which are escalated in cohorts of 3 patients at the dose levels of 0.01, 0.04, 0.15, 0.5, 1.5, 4.5 and 7.0 mg/kg. Study objectives are the assessment of safety and tolerability, PK, immunogenicity, antitumor activity, as well as the determination of the maximum tolerated dose (MTD) or the optimal biological dose (OBD). The safety of the MTD or OBD will be confirmed in further patients receiving 2 cycles of AFM13. AM13 was shown to be safe and well tolerated by highly pre-treated Hodgkin Lymphoma patients in weekly doses of up to 7.0 mg/kg. Adverse events were generally mild, with the most frequent drug-related event being fever. An objective response was achieved on the dose level 1.5mg/kg. Nine cases of stable disease/minor response were also observed. In ex vivo assays AFM13 restored impaired cytotoxic activity of NK cells from HL patients. Preclinical and interim clinical data will be presented, showing that AFM13 may become a safe and effective targeted therapy for CD30 positive malignancies. Disclosures E. Zhukovsky: The author is the employee of Affimed Therapeutics and the member of the Management Board, M. Ravic: A consultant to Affimed Therapeutics and a Chief Medical Officer, M. Topp: Consultant to Affimed, S. Knackmuss: The coauthor is an employee of the company. U. Reusch: The coauthor is an employee of the company. E. Rajkovic: The coauthor is an employee of the company. C. Hucke: The co-author is a former employee of Affimed Therapeutics and currently is a clinical development consultant M. Little: The co-author is a consultant to Affimed Therapeutics and owns the warrants of the company.