Nkarta announces updated data from Phase 1 study of NKX101

Nkarta announced updated data from its Phase 1 study of NKX101 to treat patients with relapsed or refractory acute myeloid leukemia. NKX101 is an allogeneic, off-the-shelf cell therapy candidate comprising NK cells derived from healthy donors and engineered to target NKG2D ligands on cancer cells. Four of six patients in one dose expansion cohort achieved a best composite complete response after receiving at least one cycle of NKX101. In this cohort, a cycle consisted of three weekly doses of NKX101 at 1.5 billion cells per dose after treatment with fludarabine and Ara-C for lymphodepletion. Ara-C is an established and important drug in the treatment of AML across treatment lines, including first line therapy. Exposure to Ara-C is also known to upregulate NKG2D ligands, potentially increasing sensitivity of cancerous cells to NK-cell mediated killing. Data from the NKX101 study suggest Ara-C has the potential to be an effective agent for lymphodepletion. Nkarta expects to enroll 12 to 20 additional patients in the expansion cohort using Flu/Ara-C lymphodepletion of the Phase 1 clinical trial and provide a clinical update in the first half of 2024. Nkarta also plans to introduce protocol changes intended to standardize criteria for retreatment and consolidation and simplify study logistics for enrolled patients. NKX101 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses donor-derived NK cells engineered to target NKG2D ligands on cancer cells. NKX101 is being evaluated in a dose-escalation Phase 1 study as a multi-dose, multi-cycle cellular therapy in patients with r/r AML. As of June 10, 2023, a total of 36 patients with r/r AML were enrolled, compared to 17 at the previous update of April 21, 2022. Thirty patients with r/r AML were treated with NKX101 after lymphodepletion with fludarabine and cyclophosphamide, through dose finding and a separate dose expansion cohort. The majority of patients had poor risk disease. The patients in these cohorts were heavily pre-treated, with 2 median lines of therapy and 27/30 having been treated with venetoclax. A separate, expansion cohort enrolled 6 patients who received lymphodepletion with Flu/Ara-C followed by 3 weekly doses of NKX101 at 1.5 billion cells per dose. This cohort included 5/6 patients with poor risk disease and other additional high-risk clinical features such as early relapse after allogeneic hematopoietic cell transplant and chemo-refractory disease. The patients in this cohort were also heavily pre-treated, with 2 median lines of therapy and all having been previously treated with venetoclax-containing regimens. NKX101 was well tolerated. No dose-limiting toxicities were observed across all cohorts. The safety profile of NKX101 was consistent across both lymphodepletion regimens. The emerging safety profile of NKX101 is positively differentiated from those of many cell therapies. In patients with r/r AML that received lymphodepletion with Flu/Cy, limited CAR T-like toxicities were observed, including 5 less than or equal tograde 2 infusion reactions, 5 cases of less than or equal tograde 2 cytokine release syndrome, 1 case of grade 2 immune effector cell-associated neurotoxicity syndrome, and no graft-versus-host disease. The most common higher-grade adverse events were myelosuppression – a condition resulting in fewer red blood cells, white blood cells and platelets, as well as infection, which are common in this patient population post lymphodepletion. In patients with r/r AML in the expansion cohort using Flu/Ara-C lymphodepletion, there were no observations of CRS, ICANS or GvHD of any grade. Myelosuppression and infection remained the most common higher-grade adverse events. However, there were no greater thangrade 3 infections, and no treatment-associated fatalities. In patients with r/r AML that received Flu/Ara-C lymphodepletion, 4 of 6 achieved CR/CRi and 3 of 6 achieved a complete response with hematologic recovery. Two of the 4 reported complete responses were MRD negative. MRD negativity is broadly viewed as an important quantitative measure of disease burden in AML and is associated with increased disease-free survival and decreased risk of recurrence. One patient with MRD positive CR underwent allogeneic HCT and remains in CR at 4 months. Another patient with CR has no detectable disease by flow cytometry and additional MRD testing is pending. Flu and Ara-C are often combined with other chemotherapies, such as idarubicin and mitoxantrone in r/r AML, and such combinations have been used as a part of comparator arms in multiple registrational studies, with CR rates between 10-12%. In patients with r/r AML that received Flu/Cy lymphodepletion, and the highest doses of NKX101, 4 of 18 achieved CR/CRiand 3 of 18 achieved a complete response with hematologic recovery CR. There were no CRs at the lower doses of NKX101.