Abstract CT341: AFM13: an antigen specific immunotherapy for the treatment of CD30+ malignancies: Results of first-in-man study in relapsed/refractory (R/R) Hodgkin lymphoma (HL)
Authors: Rothe Achim , Reiners Katrin S. , Topp Max S. , Younes Anas , Tresckow Bastian von , Hummel Horst Dieter , Kessler Joerg , Ravic Miroslav , Marschner Jens-Peter , Strandmann Elke Pogge von , Engert Andreas 
Published: May 2015

Abstract
Introduction: Standard treatment of HL results in high cure rates. However, 30-40% of the patients relapse and 2nd line therapies induce durable remission in only 50% of the patients. AFM13 is a novel, tetravalent bi-specific antibody belonging to Affimed's RECRUIT TandAb platform. AFM13 recruits NK-cells to kill CD30+ tumor cells by targeting CD30 and CD16A. Due to promising pre-clinical data a phase I study was conducted.
Method: Patients with R/R HL that underwent all standard therapy received stepwise escalated doses of i.v. AFM13 from 0.01 to 7.0 mg/kg weekly over 4 weeks (=1 cycle). A small cohort of patients received 4.5 mg/kg of AFM13 twice weekly over 4 weeks. The primary objectives were safety and tolerability, secondary objectives were pharmacokinetics (PK), pharmacodynamics (PD), and efficacy. PD was assessed in plasma and included activated NK cells measured by CD69 expression and soluble CD30 (sCD30). PK was measured after the first infusion for all regimens plus on day 25 (last infusion) for the twice weekly regimen. Tumor response was measured using Cheson criteria 4 weeks after end of treatment.
Results: 24 patients received AFM13 weekly, 5/24 patients received a 2nd cycle. 4 patients were treated twice weekly. AFM13 was well tolerated with mainly mild to moderate adverse events (AEs). The maximum tolerated dose was not reached. One dose limiting toxicity (DLT) was observed in the 0.5 mg/kg cohort: hemolytic anemia CTCAE Grade 4. No further DLTs were observed even at higher doses. The most common AEs were pyrexia (53.6%) and chills (39.3%). 8 patients (26.8%) experienced serious AEs. PK data revealed a dose proportional increase of systemic exposure. AFM13 was detectable in plasma up to 168 h (highest dose) with a half-life of 10-22 hours. AFM13 treatment resulted in an increase of CD69+ NK cells which was more pronounced at doses ≥1.5 mg/kg. The kinetics of NK cell activation correlated with PK. In 24/28 patients sCD30 levels decreased during treatment. All patients receiving ≥1.5 mg/kg of AFM13 had a marked decrease of sCD30. 26/28 patients were eligible for efficacy evaluation. 3 patients had a partial remission (PR), 13 had stable disease (SD) and 10 had disease progression. Overall, the clinical effect was more pronounced in cohorts receiving ≥1.5 mg/kg with an overall response rate of 23% (3/13). Importantly, 6/7 patients who were refractory to most recent brentuximab vedotin therapy achieved SD under AFM13 treatment.
Conclusion: AFM13 was well tolerated and demonstrated activity in terms of PD and tumor response. PK data indicate that the dose regimen has to be optimized and that the measured clinical effect is likely to underestimate the potency of AFM13 in HL. A phase II study with a modified dose regimen is in preparation.
Citation Format: Achim Rothe, Katrin S. Reiners, Max S. Topp, Anas Younes, Bastian von Tresckow, Horst Dieter Hummel, Joerg Kessler, Miroslav Ravic, Jens-Peter Marschner, Elke Pogge von Strandmann, Andreas Engert. AFM13: an antigen specific immunotherapy for the treatment of CD30+ malignancies: Results of first-in-man study in relapsed/refractory (R/R) Hodgkin lymphoma (HL). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT341. doi:10.1158/1538-7445.AM2014-CT341