Updated clinical data from phase I/II study of AFM13 complexed with preactivated and expanded cord blood-derived NK cells for patients with R/R CD30+ lymphoma

Data obtained from the ongoing AFM13 trial demonstrates that natural killer (NK) cells derived from donated umbilical cord blood, combined with a novel bispecific antibody known as AFM13 that targets CD16A and CD30, achieved effective responses in patients with pretreated and refractory CD30⁺ lymphoma. Below, we summarize the data as presented at the AACR Annual Meeting 2022.¹

AFM13 is a bispecific antibody designed to bind to CD30 on lymphoma cells and CD16A on NK cells, this allows NK cells to effectively target and remove cancer cells. This technology utilizes a combination approach; NK cells are isolated from donated umbilical cord blood, activated using cytokines, and expanded alongside artificial antigen-presenting cells. These are subsequently complexed with AFM13 prior to infusion (AFM13-NK).

A total of 22 patients were enrolled in the trial, 19 of whom were evaluable for response. Patients enrolled were multi-refractory with a median of seven prior lines of treatment.All had active progressive disease at enrollment, and none received bridging therapy. Patients were enrolled at 3 dose levels: 10⁶ NK/Kg, 10⁷ NK/Kg and 10⁸ NK/Kg. Treatment cycles began with lymphodepleting chemotherapy, followed 2 days later by a single infusion of AFM13-NK. Three weekly infusions of AFM13 monotherapy were subsequently administered.

Key findings

• 89% overall response rate
• 81% overall survival rate
• 51% progression-free survival
• Expansion of NK cells initiated upon infusion and continued for 2 weeks
• Dose Level 3 (108 NK/Kg) was established as the recommend phase II dose

The treatment was well tolerated and demonstrated an acceptable safety profile, with no instances of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease. There were no cases of infusion-related reaction in 40 infusions of AFM13-NK. The recommended phase II dose was established at 10⁸ NK/Kg – all 13 patients treated at this dose had a response by LYRIC criteria.

This trial represents the first of its kind to use off-the-shelf cord blood-derived cytokine-induced memory-like ex vivo expanded NK cells precomplexed with the AMF13 construct to treat patients with CD30⁺ relapsed/refractory lymphomas. It is hoped that AMF13-NK could offer a new therapeutic option for this patient population with an established unmet need.