title: A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma.
abstract: AFM13 is a bispecific, tetravalent chimeric antibody construct (TandAb) designed for the treatment of CD30-expressing malignancies. AFM13 recruits natural killer (NK) cells via binding to CD16A as immune effector cells. In this phase 1 dose-escalation study, 28 patients with heavily pretreated relapsed or refractory Hodgkin lymphoma received AFM13 at doses of 0.01 to 7 mg/kg body weight. Primary objectives were safety and tolerability. Secondary objectives included pharmacokinetics, antitumor activity, and pharmacodynamics. Adverse events were generally mild to moderate. The maximum tolerated dose was not reached. Pharmacokinetics assessment revealed a half-life of up to 19 hours. Three of 26 evaluable patients achieved partial remission (11.5%) and 13 patients achieved stable disease (50%), with an overall disease control rate of 61.5%. AFM13 was also active in brentuximab vedotin-refractory patients. In 13 patients who received doses of ≥1.5 mg/kg AFM13, the overall response rate was 23% and the disease control rate was 77%. AFM13 treatment resulted in a significant NK-cell activation and a decrease of soluble CD30 in peripheral blood. In conclusion, AFM13 represents a well-tolerated, safe, and active targeted immunotherapy of Hodgkin lymphoma. A phase 2 study is currently planned to optimize the dosing schedule in order to further improve the therapeutic efficacy. This phase 1 study was registered at www.clinicaltrials.gov as #NCT01221571.
authors.affiliation: Department I of Internal Medicine, and Innate Immunity Group, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany;
authors.forename: Achim
authors.initials: A
authors.lastname: Rothe
authors.affiliation: Department I of Internal Medicine, and.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Sasse
authors.affiliation: Department of Internal Medicine II, Division of Hematology and Medical Oncology, Wuerzburg University Medical Center, Wuerzburg, Germany;
authors.forename: Max S
authors.initials: MS
authors.lastname: Topp
authors.affiliation: Department I of Internal Medicine, and.
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Eichenauer
authors.affiliation: Department of Internal Medicine II, Division of Hematology and Medical Oncology, Wuerzburg University Medical Center, Wuerzburg, Germany;
authors.forename: Horst
authors.initials: H
authors.lastname: Hummel
authors.affiliation: Innate Immunity Group, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany;
authors.forename: Katrin S
authors.initials: KS
authors.lastname: Reiners
authors.affiliation: Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany; and.
authors.forename: Markus
authors.initials: M
authors.lastname: Dietlein
authors.affiliation: Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany; and.
authors.forename: Georg
authors.initials: G
authors.lastname: Kuhnert
authors.affiliation: Innate Immunity Group, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany;
authors.forename: Joerg
authors.initials: J
authors.lastname: Kessler
authors.affiliation: Department I of Internal Medicine, and.
authors.forename: Carolin
authors.initials: C
authors.lastname: Buerkle
authors.affiliation: Affimed, Heidelberg, Germany.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Ravic
authors.affiliation: Affimed, Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Knackmuss
authors.affiliation: Affimed, Heidelberg, Germany.
authors.forename: Jens-Peter
authors.initials: JP
authors.lastname: Marschner
authors.affiliation: Innate Immunity Group, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany;
authors.forename: Elke
authors.initials: E
authors.lastname: Pogge von Strandmann
authors.affiliation: Department I of Internal Medicine, and.
authors.forename: Peter
authors.initials: P
authors.lastname: Borchmann
authors.affiliation: Department I of Internal Medicine, and.
authors.forename: Andreas
authors.initials: A
authors.lastname: Engert
mesh_terms: D000328:Adult; D000368:Aged; D018033:Antibodies, Bispecific / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D017730:Ki-1 Antigen / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000276:immunology; D012008:Recurrence; D055815:Young Adult
chemical_list: D018033:Antibodies, Bispecific; C496124:FCGR3A protein, human; D017730:Ki-1 Antigen; D017452:Receptors, IgG