Nkarta cell therapy spurs responses in blood cancer, but specific preconditioning needed

Nkarta Therapeutics’ off-the-shelf natural killer cell therapy appears to be most effective against blood cancer when used with a specific lymphodepletion regimen. But that’s not what most patients have received so far.  

NKX101 was found to spur a complete response in four out of six patients with relapsed or refractory acute myeloid leukemia that received the treatment in addition to cytarabine and fludarabine, according to a release posted Tuesday. Three out of six patients had a complete response with hematologic recovery. The durability of the treatment remains an open question as none of the six patients have been in the study for six months yet. 

The findings in this dose expansion cohort are encouraging, but mean the company is having to pivot slightly to recruit more patients for this regimen. Nkarta hopes to recruit 12 to 20 more patients to receive the cell therapy and specific lymphodepletion combo and expects more data in the first half of 2024. 

The vast majority of patients to date, however, have received fludarabine and cyclophosphamide to wipe out T cells. And that combination, in addition to NKX101, has yet to prove its mettle. Nkarta reported that 22% of patients receiving this regimen at the highest NKX101 dose level had a complete response and no complete responses were recorded at the lowest level of the cell therapy. 

The safety profile of the more encouraging lymphodepletion regimen so far has a slight edge, as well. There have been no reports of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome and graft versus host disease among the six patients treated so far. Five cases of grade 2 or lower cytokine release syndrome were reported among patients given fludarabine and cyclophosphamide, plus one case of immune effector cell-associated neurotoxicity syndrome. 

The latest clinical update has evidently not impressed investors, with Nkarta’s shares down 27% shortly after the market opened, from $4.53 to $3.30. In the last year, the biotech’s share price has fallen more than 70%. 

Nkarta is in a competitive race to develop the first allogeneic cell therapy to treat cancer, battling the likes of Caribou Biosciences, Precision Biosciences and Allogene who are working on off-the-shelf CAR-Ts. The potential benefit to natural killer cells over T-cells is that they are equipped with more tumor-killing spontaneity and could be more effective in antigen down regulation environments. In addition to NKX101, Nkarta has a CD19-targeting cell therapy in the clinic for patients with B-cell malignancies and is anticipating a clinical update in the second half of the year.