NKX101

P1, N=61, Active, not recruiting, Nkarta Inc. | Recruiting --> Active, not recruiting | N=90 --> 61

ConclusionsIn summary, we show that NKX101 potently targets and eliminates AML cells expressing NKG2D-Ls further validating NKG2D-Ls as therapeutic targets. Additionally, we show that the combination of Ara-C and NKX101 leads to increased anti-leukemic activity, supporting continued investigation of NKX101 CAR NK cell therapy after lymphodepletion incorporating Ara-C for the treatment of r/r AML.

Additionally, the ability of NKX101 to potently kill AML LSC blasts suggests that NKG2D-L targeting may be a viable mechanism for eliminating LSC in the blood and bone marrow of patients with r/r AML. Taken together, these data support NKG2D-Ls as promising therapeutic targets for AML and support further investigation of NKX101 CAR NK cell therapy for the treatment of r/r AML.

Because Ara-C is known to upregulate NKG2D ligand expression, use of Flu/Ara-C as an alternative to standard Flu/cyclophosphamide (Flu/Cy) for lymphodepletion (LD) was tested for NKX101...Patients had received a median of two prior lines of therapy, with all patients having previous venetoclax exposure (Table 1)...Despite being an allogeneic, non-HLA-matched cell product, NKX101 persisted for up to three weeks in PK testing. Directly comparing the data from patients treated with Flu/Cy with NKX101 versus Flu/Ara-C with NKX101 suggests that Flu/Ara-C can replace the Flu/Cy regimen common to CAR T cell therapy as LD without compromising overall NKX101 exposure.

P1, N=90, Recruiting, Nkarta Inc. | Trial completion date: Jul 2038 --> Jul 2039 | Trial primary completion date: Jul 2023 --> Jul 2024

We demonstrate that cetuximab increases the anti-tumor effect of NKX101 in a dose-dependent manner. Assessment of the interaction between NKX101 and cetuximab in vitro revealed that the two agents can combine to kill cancer cells in a synergistic manner. Blocking CD16 on NKX101 cells with a neutralizing antibody significantly decreased potency of the combination, suggesting that the improvement in potency observed is a direct result of CD16-mediated ADCC activity.

P1, N=90, Recruiting, Nkarta Inc. | N=64 --> 90

The starting dose of NKX101 is 1×108 CAR NK cells where NKX101 will be administered on Days 0, 7, and 14 of a 28‑day cycle following standard fludarabine/cyclophosphamide lymphodepletion. Results The trial is in progress. Conclusion NKX101 is a novel fourth generation allogeneic CAR NK being evaluated in a Phase 1 trial with R/R AML or higher risk MDS patients at multiple centers (NCT04623944).

CAR NKG2D NK cells demonstrate enhanced in vitro and in vivo cytotoxicity against CRC and HCC cell lines . Significant tumor control using regional delivery in initial studies support continued clinical development . NKX101 is an investigational agent comprised of CAR NKG2D NK cells being evaluated in a phase 1 clinical study for treatment of relapsed/refractory acute myeloid leukemia or higher risk myelodysplastic syndrome .

The starting dose of NKX101 is 1 × 108 viable CAR NK cells where NKX101 will be administered on Days 0, 7, and 14 of a 28‑day cycle following standard fludarabine/cyclophosphamide lymphodepletion...Exploratory endpoints are correlation of various degrees of HLA and KIR ligand match/mismatch between donor and recipient with primary and secondary safety, PK, and efficacy measures. Enrollment across multiple US sites is expected to start in late 2020.

NKX101 demonstrated improvements in in vitro cytotoxicity and pro-inflammatory cytokine release. RD techniques in vivo revealed increased cell delivery and improved tumor control. Further studies are underway to confirm our initial findings and understand NKX101 cellular kinetics and susceptibility to immunosuppression in the liver, along with planned clinical evaluation in Phase 1 trials.