On December 5, 2022 Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer cell therapies to treat cancer, reported positive updated data from its Phase 1 dose escalation study of NKX019 as monotherapy to treat patients with relapsed or refractory (r/r) non-Hodgkin lymphoma (NHL) (Press release, Nkarta, DEC 5, 2022, View Source [SID1234624771]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Seven of ten patients treated at the higher dose levels in a three-dose regimen showed a complete response (70% CR), including two patients with aggressive large B cell lymphoma (LBCL), one patient with mantle cell lymphoma (MCL), and one patient with marginal zone lymphoma (MZL). No dose limiting toxicity, neurotoxicity / ICANS, graft versus host disease (GvHD), or >Gr3 cytokine release syndrome (CRS) were observed in the study.
"NKX019 continues to demonstrate impressive single-agent activity, preliminary durability and an encouraging safety profile as an off-the-shelf, on-demand cell therapy for heavily pre-treated patients with NHL," said Paul J. Hastings, President and CEO of Nkarta. "Based on this initial success, we recently opened dose expansion cohorts to explore combination and single-agent regimens in patients with LBCL, an especially aggressive form of lymphoma, and to address the large unmet need in patients who have received prior autologous CAR T therapy. We remain committed to improved access for patients through the integration of cell therapy into the broader outpatient setting."
Nkarta plans to provide updates from the NKX019 program, including data from the dose expansion cohorts, in 2023.
Evaluating NKX019 in r/r B cell malignancies
NKX019 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses NK cells engineered to target the B-cell antigen CD19, a clinically validated target for B-cell cancer therapies. The NKX019 Phase 1 study is evaluating the safety and anti-tumor activity of NKX019 as a multi-dose, multi-cycle therapy in patients with r/r B cell malignancies.
As of November 28, 2022, 19 patients were enrolled and dosed. Fourteen patients entered the study with a diagnosis of non-Hodgkin lymphoma (NHL), 7 of which were aggressive large B cell lymphoma (LBCL). Patients had received a median of 4 prior lines of therapy (range of 2 to 10). To date, enrollment has included patients with aggressive disease characteristics and extensive lesions throughout the body. Patients were enrolled at clinical trial sites in Australia (13) and the United States (6).
"Autologous CAR T cell therapy has undeniably changed the NHL treatment landscape, but the possibility of severe toxicity and the limited access of these therapies leave many potentially eligible patients without a cellular therapy option," said Michael Dickinson, M.D., Lead, Aggressive Lymphoma disease group, Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, and investigator in the NKX019 trial. "In the data so far, NKX019 has shown encouraging anti-tumor activity, including in patients with aggressive histologies, who are the patients who are most in need."
Safety in NKX019
NKX019 was well tolerated. No ICANS, GvHD, or >Gr3 CRS were observed in the study. No dose-limiting toxicities were observed. Five patients developed fever within 8 hours of NKX019 infusion, and each resolved within 24 hours. 2 of the 5 patients were assessed to have infusion-related reactions, 2 patients were assessed to have CRS, despite the rapid onset and rapid resolution not common in CRS, and one patient had both entities described in two separate cycles. The most common higher-grade adverse events were myelosuppression – a condition resulting in fewer red blood cells, white blood cells and platelets, which is common in this patient population post lymphodepletion. (See table 1.) The emerging safety profile of NKX019 is positively differentiated from those of many cell therapies.
NXK019 Safety (Table 1)
Grade 3/4 AEs in > 1 subject Total (N=19)
Subjects with any ≥ Grade 3 AEs 16 (84%)
Neutrophil count decreased 12 (63%)
Platelet count decreased 8 (42%)
Febrile neutropenia 5 (26%)
Anemia 4 (21%)
WBC count decreased 3 (16%)
Lymphocyte count decreased 2 (11%)
Treatment emergent adverse events regardless of relationship based on interim data from open clinical database as of 28 November 2022
Clinical Activity in NXK019
Nineteen patients who received NKX019 were assessed (See table 2). In the two highest dose cohorts (1 B cells x 3 and 1.5 B cells x 3), 8 out of 10 patients with NHL achieved an objective response (80% ORR) and 7 out of 10 achieved a complete response (70% CR). 5 of 6 patients with NHL in the cohort receiving 3 doses of 1 billion cells achieved a response (83% ORR), and 4 of 6 achieved a complete response (67% CR rate). 3 of 4 patients with NHL in the cohort receiving 3 doses of 1.5 billion cells achieved a response (75% ORR) and a complete response (75% CR). For all cohorts in the dose finding portion (300 M cells x 3, 1 B cells x 3, and 1.5 B cells x 3), 10 of 14 patients with NHL achieved an objective response (71% ORR) and 8 of 14 achieved a complete response (57% CR). 3 patients with ALL and 2 patients with CLL were treated, with no response observed.
NKX019 Clinical Activity (Table 2)
300 M cells x 3 1 B cells x 3 1.5 B cells x 3
ORR (CR, PR) CR ORR (CR, PR) CR ORR (CR, PR) CR
All NHL 2/4 (50%) 1/4 (25%) 5/6 (83%) 4/6 (67%) 3/4 (75%) 3/4 (75%)
LBCL# 1/3 0/3 1/2 1/2 1/2 1/2
MCL - - 1/1 1/1 - -
FL 1/1 1/1 2/2 1/2 2/2 2/2
MZL - - 1/1 1/1 - -
Leukemia
ALL 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/2 (0%) - -
CLL - - - - 0/2 [1/2 SD] 0/2
#LBCL includes DLBCL and FL3b
ALL: acute lymphoblastic leukemia; CLL: chronic lymphocytic leukemia; CR: complete response; FL: follicular lymphoma; LBCL: large B-cell lymphoma; MCL: mantle cell lymphoma; MZL: marginal zone lymphoma; NHL: non-Hodgkin lymphoma; ORR: overall response rate; PR: partial response
About the NKX019 Clinical Trial
NKX019 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses natural killer (NK) cells engineered to target the B-cell antigen CD19, a clinically validated target for B-cell cancer therapies. The dose-finding portion of the NKX019 Phase 1 study evaluates the safety and anti-tumor activity of NKX019 as a multi-dose, multi-cycle monotherapy following lymphodepletion in patients with r/r B-cell malignancies. Patients must have received at least two prior therapies. Patients that received prior autologous CAR-T therapy were not eligible.
Patients in the NKX019 trial received a cycle of treatment consisting of lymphodepletion with 3 days of fludarabine and cyclophosphamide followed by NKX019 cells in a three-dose regimen where cells were given on Days 0, 7, and 14. Patients received doses of 300 million, 1 billion, or 1.5 billion cells three times in a cycle. Based on tumor response and tolerability assessment, patients are eligible to receive additional treatment cycles, including patients with progressive disease to observe whether NKX019 can reverse progression. Disease assessment was performed by investigator review according to the 2014 Lugano response criteria for patients with NHL and NCCN response criteria for patients with ALL.
The dose-expansion portion of the Phase 1 clinical trial of NKX019 will investigate NKX019 as combination therapy with rituximab, an anti-CD20 monoclonal antibody, in patients with r/r non-Hodgkin lymphoma, as well as NKX019 as monotherapy in patients with large B-cell lymphoma (LBCL) who previously received autologous CD19 CAR T-cell therapy. The dose expansion will also further investigate NKX019 as monotherapy in patients with LBCL who have not previously received autologous CD19 CAR T-cell therapy.
Conference Call Information
Nkarta management will discuss the NKX019 results on Monday, December 5, 2022, at 8:00 a.m. ET. To access the live webcast, please register online on the Investors section of Nkarta’s website: View Source An archived webcast and accompanying slides will be available on the Company’s website approximately two hours after the event.
About NKX019
NKX019 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy adult donors. It is engineered with a humanized CD19-directed CAR for enhanced tumor cell targeting and a proprietary, membrane-bound form of interleukin-15 (IL-15) for greater persistence and activity without exogenous cytokine support. CD19 is a biomarker for normal and malignant B cells, and it is a validated target for B cell cancer therapies. To learn more about the NKX019 clinical trial in adults with advanced B cell malignancies, please visit ClinicalTrials.gov.