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

Abstract

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.

Conflict of interest statement

Conflict-of-interest disclosure: N.L.B. reports grant funding from Affimed, BMS, and Merck; A.F.H. reports grant funding from AstraZeneca, BMS, Gilead, Immune Design, KiTe Pharma, Merck, and Seattle Genetics, and personal fees from Adaptive Biotechnologies, BMS, Genentech, KiTe Pharma, Merck, and Seattle Genetics; E.D.-D. reports personal fees from BMS and Takeda and nonfinancial support from Roche and Takeda; S.M.A. reports grant funding from Affimed, AI Therapeutics, BMS, Regeneron, Seattle Genetics, and Trillium; A.M. reports grant funding from Affimed, ADC Therapeutics, ASTEX, BMS, Celgene, FortySeven Inc., Gilead, Incyte, KiTe Pharma, Juno, Merck, Oncotartis, Pharmacyclics, Rhizen, Roche-Genentech, Seattle Genetics, and Takeda, and personal fees from AstraZeneca, BMS, Celgene, Gilead, KiTe Pharma, Juno, Pharmacyclics, and Seattle Genetics; A.F.-T. reports grant funding by UAB and is a former employee of Seattle Genetics; R.G.-S. reports clinical grant funding from Takeda and University Hospital of Salamanca, CME fees from the Spanish Society of Hematology, personal fees from Beyond Spring, Janssen-Cilag, Roche, and Takeda, and grant funding from Gilead; P.A. reports consultancy services from Affimed, Adaptive, ADC Therapeutics, BMS, Celgene, Merck, Morphosys, and Pfizer, grant funding from Affimed, Adaptive, BMS, Genentech, IGM, Merck, Otsuka, Tensha, and Sigma τ, and personal fees from BMS and Merck; and S.E.S., L.A., A.S., K.P., and C.C.-J. are employees of Affimed. The remaining authors declare no competing financial interests.

© 2020 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Best response according to tumor volume. The dashed line (−30%) represents clinically meaningful responses (30% reduction from baseline). *All assessments are based on CT scan, CRs are based on PET scans (metabolic assessment) and appear opaque on CT scans. NE, not evaluable; PR, partial response; SD, stable disease.

Figure 2.

Duration and deepening of responses.