A Phase I Study Of An Anti-CD30 x Anti-CD16A Bispecific Tandab Antibody, AFM13, In Patients With Relapsed Or Refractory Hodgkin Lymphoma

• Published in: Blood 2013-11, Vol.122 (21), p.5116-5116
• Main Authors: Zhukovsky, Eugene, Rothe, Achim, von Tresckow, Bastian, Topp, Max, Younes, Anas, Eichenauer, Dennis A., Hummel, Horst, Reiners, Katrin S., Dietlein, Markus, Kessler, Joerg, Ravic, Miroslav, Hucke, Christian, Strandmann, Elke Poggevon, Engert, Andreas
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V122.21.5116.5116

AFM13 is a bispecific TandAb antibody for the treatment of Hodgkin lymphoma (HL) and other CD30+ malignancies. AFM13 specifically targets both CD30, which is the antigen identifying HL tumor cells, and CD16A, for the recruitment of NK cells. Our preclinical data demonstrate a specific and potent anti-tumor activity mediated by the engagement of NK immune effector cells. AFM13 was investigated in an open-label single-arm phase I dose escalation trial in patients with relapsed/refractory HL. The objective of this study was to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, anti-tumor activity, and maximum tolerated dose (MTD). Each patient received 4 weekly doses of AFM13. Seven dose levels, from 0.01 to 7.0 mg/kg, were escalated in cohorts of 3 patients. In addition, one cohort of 4 patients received AFM13 twice a week at 4.5 mg/kg for 4 weeks. Twenty-eight (28) HL patients were enrolled, and these heavily pre-treated patients had a median number of six (6) prior therapies. 14/28 patients were refractory to their most recent therapy. 9/28 patients had a prior therapy with brentuximab vedotin. AFM13 was safe and well-tolerated, and did not reach the MTD. One dose-limiting toxicity (DLT) was observed at 0.5 mg/kg, and this dose cohort was expanded to 6 patients. No further DLTs were observed. The most frequent adverse events were infusion-related reactions (headache, fever, fatigue and myalgia) that often occurred after the first administration. Nearly all adverse events were short-lived. According to the Cheson criteria, 2 patients achieved partial responses and 13 patients achieved stable disease. In addition, AFM13 was active in brentuximab vedotin relapsing/refractory patients, with 7 out of 9 patients achieving stable disease after AFM13 treatment. The responses of the 13 patients who received AFM13 at and above the 1.5 mg/kg dose level were further analyzed for pharmacodynamic/anti-tumor activity correlations. In this group the drug exhibited substantial anti-tumor activity, with 8 out of the 13 patients experiencing a reduction in both tumor volume (as assessed by CT scan) and tumor activity (as assessed by FDG-PET scan imaging). Furthermore, 3 out of the 13 patients (23%) exhibited a reduction in tumor volume of more than 50%. The on-mechanism activity of the drug was further substantiated by the NK cell activation and soluble CD30 clearance pharmacodynamic parameters. Statistically significant correlations between increasing anti