ASH 2023 | A Phase I trial investigating a novel oral FLT3 inhibitor, BMF-500, in FLT3-mutant AML

So at this ASH meeting, we are also presenting the results preliminarily of a Phase I study of CYNK-001. This is a placental NK-cell product which is designed for adoptive T-cell therapy. We know that in acute myeloid leukemia, unlike acute lymphocytic leukemia or myeloma or lymphoma, it’s been very challenging to develop CAR-T constructs or CAR-T products that have efficacy, and this may be because the T-cell axis in these malignancies is not quite as potent or active. And so can we look at other infusions of immune cells, NK-cells being one example, where they’re not HLA restricted and play a role in mediating tumor burden outside of traditional T-cell pathways.

So, in this study, the design is to give patients with relapsed or refractory AML or MRD-positive AML infusions of placental NK-cells after different conditioning regimens. Patients in the initial cohorts of the study received just a fludarabine/cyclophosphamide conditioning regimen, which was altered in later cohorts. And the study looked at multiple doses of NK-cell product, up to four doses. At the highest dose levels, patients were receiving 1.8 million cells times four infusions for treatment of their disease.

This study was planned for up to 30 participants. Out of 28 patients presented at this meeting, there was evidence that there was some efficacy at the highest dose level. Two of four patients achieved evidence of response, with one patient achieving a MRD negative CR from their relapsed/refractory AML that lasted over 210 days. There is also one patient in the MRD-positive cohort who cleared MRD disease after NK-cell infusion.

The study is now closed to accrual and the results are being written up for publication purposes. I think it validates that NK-cell infusions of this method after standard conditioning can be tolerably given. There was no evidence of significant cytokine release or neurological toxicities, and multiple doses of NK-cell infusions were able to be given. Correlative studies were looking at T-cells and the microenvironment of these patients. I think, future generations of this product will need to be explored to further enhance the potency, but I think this early study does establish that this can be a valid target with some signs, early signs, of clinical efficacy.