ASH 2022 | A Phase I/II study of AFM13 in combination with cord blood-derived NK cells in patients with R/R HL

So this trial was based on our hypothesis that pre-complexing allogeneic cord blood-derived NK cells with AFM13, which is an antibody construct with bispecificity for CD30 on the lymphoma cells and CD16A on the NK cells would engage the NK cells in an immunological synapse and increase cytotoxicity on the target cell via cytotoxic granules. So this hypothesis we had studied in the lab and we saw that preactivating and expanding with cytokines, the cord blood NK cells led to, and then incubating them with AFM13, which is this tetravalent bispecific antibody construct, led to much greater tumor shrinkage and better results in mice bearing CD30 positive lymphomas compared to the same preactivated and expanded NK cells without the AFM13 or mice treated with AFM13 alone. So that led to a clinical trial where we basically enrolled patients with CD30 positive lymphomas who had failed brentuximab vedotin.

And over the course of two weeks, we preactivated and expanded the NK cells from a cord blood unit and then incubated them with AFM13. And during that time, patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide. They received the AFM13 pre-complexed NK cells, and we saw that, number one, the treatment was extremely well tolerated with no instances of cytokine release syndrome, ICANS, neurotoxicity or GvHD. And we saw a very high level of activity with 94% responses and 71% complete responses in a very heavily pretreated population exposed to a median three prior lines of therapy, I’m sorry, seven previous lines of therapy with almost 80% having failed an autologous or an allogeneic stem cell transplant. So we think this is a very safe and very active regimen in this population with heavily pretreated CD30 positive lymphomas.