Abstract
Abstract Introduction: 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) V/F polymorphism and (ii) non-selective binding to immune effector cells vs. granulocytes via CD16B receptor. Furthermore, RECRUIT-TandAbs have significant advantages over other antibody fragment technologies such as (i) bivalent binding to the targets and, (ii) longer half-life. Methods: AFM13 binds with high affinity to both CD30 and CD16A and is able to rapidly induce the 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. Results and Conclusion: So far, AM13 was shown to be safe and well tolerated by highly pre-treated Hodgkin Lymphoma patients in weekly doses of up to 1.5mg/kg. Adverse events were generally mild, with the most frequent drug-related event being fever. A first objective response was achieved on the dose level 1.5mg/kg. Five cases of stable disease / minor response were observed on lower dose levels. Further patients are being treated in the ongoing dose escalation study. Preclinical and interim clinical data will be presented, showing that AFM13 may become a safe and effective targeted therapy for CD30 positive malignancies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3521. doi:1538-7445.AM2012-3521
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