Excellent results for AFM13-complexed NK cells in CD30-positive lymphoma

Cord blood-derived, pre-activated, expanded natural killer (NK) cells, pre-complexed with AFM13, was a well-tolerated therapy in patients with double refractory CD30-positive lymphoma, and displayed promising anti-tumour activity at the recommended phase 2 dosing.

“AFM13 is a bispecific antibody targeting CD30 at lymphoma cells and CD16A at NK cells,” said Dr Yago Nieto (University of Texas, TX, USA). “Since autologous NK cells of patients with lymphoma are dysfunctional, the current phase 1 study (NCT04074746) pre-complexed allogeneic NK cells with AFM13 to increase the cytotoxic capacity [1].” Cord blood-derived NK cells were pre-activated with IL-12/IL-15/IL-18, expanded with universal antigen-presenting cells, K562 feeder cells, and IL-2, and pre-complexed with AFM13 (100 μg/mL). Hereafter, patients with relapsed or refractory CD30-positive lymphoma (n=41) received weekly infusions of the AFM13-complexed NK cells at 3 dose levels: 10⁶ NK/kg, 10⁷ NK/kg, 10⁸ NK/kg. The primary objectives of this study were to evaluate the safety of this approach and to establish the recommended phase 2 dose. Of note, the included patients had received a median number of 7 prior lines of therapy.

The investigational agent was well tolerated, with no cases of cytokine release syndrome, neurotoxicity, or graft-versus-host disease. Grade 3 (30%) or 4 (29%) neutropenia, and grade 3 (15%) or 4 (30%) thrombocytopenia after cycles 3 and 4 were the expected haematological toxicities. However, no bleeding events were reported. According to Dr Nieto, the phase 2 dose level was established at 10⁸ NK/kg. To continue, the 35 patients who were treated at the phase 2 dose achieved an overall response rate of 94.2%. In addition, the complete response rate was 71.4% (see Figure). Furthermore, the 6-month overall survival probability was 85% in the total population and 96% in those who received 4 cycles of the phase 2 dose (n=22).

Figure: Clinical response after first AFM13-complexed NK infusion [1]



RP2D, recommended phase 2 dose.

In conclusion, AFM13-complexed NK cells were well tolerated and resulted in high anti-tumour activity in a heavily pre-treated population of patients with CD30-positive lymphoma, supporting further investigation of this approach.

1. Nieto Y, et al. Innate Cell Engager AFM13 Combined with Preactivated and Expanded Cord Blood-Derived NK Cells for Patients with Double Refractory CD30+ Lymphoma. Abstract 168, ASH 64^th Annual Meeting, 10–13 December 2022, New Orleans, LA, USA.

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Posted on 20 February 202331 January 2024