A phase 1b study of AFM13 in combination with pembrolizumab in patients with relapsed or refractory Hodgkin lymphoma.

In relapsed/refractory Hodgkin lymphoma (R/R HL), immunotherapies such as the PD-1 inhibitor pembrolizumab have demonstrated efficacy as monotherapy and are playing an increasingly prominent role in treatment. The CD30/CD16A bispecific antibody AFM13 is an innate immune cell engager, a first-in-class, tetravalent antibody, designed to create a bridge between CD30 on HL cells and the CD16A receptor on NK cells and macrophages, to induce tumor cell killing. Early studies of AFM13 have demonstrated signs of efficacy as monotherapy for patients with R/R HL and the combination of AFM13 with pembrolizumab represents a rational new treatment modality. Here, we describe a Phase 1b, dose-escalation study to assess the safety and preliminary efficacy of AFM13 in combination with pembrolizumab in patients with R/R HL. The primary objective was estimating the MTD; the secondary objectives were to assess safety, tolerability, anti-tumor efficacy, pharmacokinetics, and pharmacodynamics. In this heavily pre-treated patient population, the combination of AFM13 and pembrolizumab was generally well tolerated, with similar safety profiles compared to the known profiles of each agent alone. AFM13 plus pembrolizumab demonstrated objective response rates of 88% at the highest treatment dose, with an 83% ORR for the overall population. Pharmacokinetic assessment of AFM13 in the combination treatment revealed a half-life of up to 20.6 hours. This proof-of-concept study holds promise as a novel immunotherapy combination worthy of further investigation. This Phase 1b study was registered at www.clinicaltrials.gov as NCT02665650.