A phase 1b study of AFM13 in combination with pembrolizumab in patients with relapsed or refractory Hodgkin lymphoma. Blood 2020 Nov 19;136(21):2401-2409
Date
07/31/2020Pubmed ID
32730586Pubmed Central ID
PMC7685206DOI
10.1182/blood.2019004701Scopus ID
2-s2.0-85094889706 (requires institutional sign-in at Scopus site) 91 CitationsAbstract
In relapsed/refractory Hodgkin lymphoma (R/R HL), immunotherapies such as the anti-programmed death-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 natural killer 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 maximum tolerated dose; the secondary objectives were to assess safety, tolerability, antitumor efficacy, pharmacokinetics, and pharmacodynamics. In this heavily pretreated patient population, treatment with the combination of AFM13 and pembrolizumab was generally well tolerated, with similar safety profiles compared to the known profiles of each agent alone. The combination of AFM13 with pembrolizumab demonstrated an objective response rate of 88% at the highest treatment dose, with an 83% overall response rate for the overall population. Pharmacokinetic assessment of AFM13 in the combination setting 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.
Author List
Bartlett NL, Herrera AF, Domingo-Domenech E, Mehta A, Forero-Torres A, Garcia-Sanz R, Armand P, Devata S, Izquierdo AR, Lossos IS, Reeder C, Sher T, Chen R, Schwarz SE, Alland L, Strassz A, Prier K, Choe-Juliak C, Ansell SMAuthor
Sumana Devata MD Associate Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Antibodies, Bispecific
Antibodies, Monoclonal, Humanized
Antigens, Neoplasm
Antineoplastic Combined Chemotherapy Protocols
Combined Modality Therapy
Dose-Response Relationship, Immunologic
Female
Half-Life
Hematopoietic Stem Cell Transplantation
Hodgkin Disease
Humans
Immunity, Innate
Immunotherapy
Ki-1 Antigen
Male
Maximum Tolerated Dose
Middle Aged
Proof of Concept Study
Receptors, IgG
Recurrence
Transplantation, Autologous
Young Adult
