Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing
engineered natural killer (NK) cell therapies, today announced
positive updated data from its Phase 1 study of NKX101 to treat
patients with relapsed or refractory (r/r) acute myeloid leukemia
(AML). 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 (67% CR/CRi rate) 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 (Flu) and Ara-C (cytarabine) 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.
“Patients with relapsed or refractory AML have few treatment
options, and novel approaches are urgently needed. Traditional
chemotherapy is often unable to drive deep remissions in this
setting, and many patients cannot tolerate it,” said Carlos
Bachier, M.D., Medical Director of Research and Cellular Therapy,
Sarah Cannon Transplant & Cellular Therapy Program at Methodist
Hospital in San Antonio, Texas. “NKX101 following lymphodepletion
with fludarabine and Ara-C had encouraging anti-tumor activity in a
small number of patients with difficult to treat
relapsed/refractory AML. This activity, together with its tolerable
safety profile, merits further study of NKX101.”
“NK cell therapy has long held promise for patients with AML,
and these latest results highlight our continued progress towards
delivering on that promise with NKX101,” said David R. Shook, M.D.,
Nkarta’s Chief Medical Officer. “While these data are early and in
a small number of patients, the response rate exceeds the rate
observed with even the latest approved agents and highlights the
potential advantages of lymphodepletion using Flu/Ara-C.”
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.
Evaluating NKX101 in r/r acute myeloid
leukemiaNKX101 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 (Flu/Cy),
through dose finding and a separate dose expansion cohort. The
majority (17/30, 57%) of patients had poor risk disease. The
patients in these cohorts were heavily pre-treated, with 2 median
lines of therapy (range 1-12) and 27/30 (90%) 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 (83%)
patients with poor risk disease and other additional high-risk
clinical features such as early relapse after allogeneic
hematopoietic cell transplant (HCT) and chemo-refractory disease.
The patients in this cohort were also heavily pre-treated, with 2
median lines of therapy (range 1-3) and all having been previously
treated with venetoclax-containing regimens. Today’s announcement
is the first time that results from the Flu/Ara-C cohort are being
presented.
Safety in NKX101 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 (Table 1), limited CAR T-like toxicities were observed,
including 5 (12%) ≤grade 2 infusion reactions, 5 (12%) cases of
≤grade 2 cytokine release syndrome (CRS), 1 case of grade 2 immune
effector cell-associated neurotoxicity syndrome (ICANS), and no
graft-versus-host disease (GvHD). 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.
Safety Table 1 – Patients treated with fludarabine /
cyclophosphamide lymphodepletion
Grade 3+ AEs in ≥10% of patients |
Total (n=30) |
Hematologic Events |
|
Thrombocytopenia |
18 (60%) |
Anemia |
16 (53%) |
Neutropenia |
13 (43%) |
Febrile neutropenia |
8 (27%) |
White blood cell count decreased |
5 (17%) |
Leukocytosis |
4 (13%) |
Infections |
|
Pneumonia |
3 (10%) |
Other |
|
Hypoxia^ |
4 (13%) |
Fatigue |
3 (10%) |
Hypotension |
3 (10%) |
|
|
Treatment emergent adverse events regardless of relationship based
on interim data from open clinical database as of 10 June
2023 |
^ In the setting of febrile neutropenia/pneumonia |
In patients with r/r AML in the expansion cohort using Flu/Ara-C
lymphodepletion (Table 2), 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
>grade 3 infections, and no treatment-associated fatalities.
Safety Table 2 – Patients treated with fludarabine /
Ara-C lymphodepletion
Grade 3+ AEs in >1 patient |
Total (n=6) |
Hematologic Events |
|
Anemia |
3 (50%) |
Febrile neutropenia |
3 (50%) |
Neutropenia |
3 (50%) |
Thrombocytopenia |
2 (33%) |
Lymphocyte count decreased |
2 (33%) |
WBC decreased |
2 (33%) |
Infections |
|
Sepsis |
3 (50%) |
Clinical Activity in NKX101 In patients with
r/r AML that received Flu/Ara-C lymphodepletion, 4 of 6 achieved
CR/CRi (67% CR/CRi rate) and 3 of 6 achieved a complete response
with hematologic recovery (50% CR rate). Two of the 4 reported
complete responses were MRD (measurable residual disease) 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 (e.g. FLAG-Ida) 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 (3 weekly doses at 1 billion or 1.5
billion cells per dose), 4 of 18 achieved CR/CRi (22% CR/CRi
rate) and 3 of 18 achieved a complete response with
hematologic recovery CR (17% CR rate). There were no CRs at the
lower doses of NKX101.
Conference Call InformationNkarta management
will discuss the NKX101 results on Tuesday, June 27, at 8:00 a.m.
ET. To access the live webcast, please register online on the
Investors section of Nkarta’s website:
https://ir.nkartatx.com/events-and-presentations. An archived
webcast and accompanying slides will be available on the Company’s
website approximately two hours after the event.
About NKX101NKX101 is an allogeneic,
cryopreserved, off-the-shelf cancer immunotherapy candidate that
uses natural killer (NK) cells derived from the peripheral blood of
healthy donors. It is engineered with a chimeric antigen receptor
(CAR) targeting NKG2D ligands on tumor cells. NKG2D, a key
activating receptor found on naturally occurring NK cells, induces
a cell-killing immune response through the detection of stress
ligands that are widely expressed on cancer cells. NKX101 is also
engineered with a membrane-bound form of interleukin-15 (IL15) for
greater persistence and activity without exogenous cytokine
support. To learn more about the NKX101 clinical trial in adults
with AML, please visit ClinicalTrials.gov.
About the NKX101 TrialThis Phase 1 clinical
trial evaluates the safety and anti-tumor activity of NKX101 as a
multi-dose, multi-cycle cellular therapy following lymphodepletion
in patients with r/r AML. Patients must have received at least one
prior therapy, and patients diagnosed with a disease mutation must
have received a targeted therapy, where approved.
Patients in the NKX101 Phase 1 trial received either fludarabine
/ cyclophosphamide lymphodepletion or fludarabine /Ara-C
lymphodepletion followed by NKX101. Patients received doses of 100
million, 300 million, 1 billion or 1.5 billion NK cells three times
in the 3-dose regimen, or doses of 150 million or 1.5 billion NK
cells two times in the 2-dose regimen. Based on tumor response and
tolerability assessment, patients were eligible to receive
additional treatment cycles. Disease assessment was performed by
investigator review according to the ELN response criteria.
About NkartaNkarta is a clinical-stage
biotechnology company advancing the development of allogeneic,
off-the-shelf natural killer (NK) cell therapies. By combining its
cell expansion and cryopreservation platform with proprietary cell
engineering technologies and CRISPR-based genome engineering
capabilities, Nkarta is building a pipeline of future cell
therapies engineered for deep anti-tumor activity and intended for
broad access in the outpatient treatment setting. For more
information, please visit the company’s website at
www.nkartatx.com.
Forward-looking statementsForward-looking
statements include, among others, statements of Nkarta’s future
expectations, plans and prospects. These may include statements
concerning Nkarta’s expectations regarding any or all of the
following: the therapeutic potential, tolerability and safety
profile of NKX101; plans and timelines for the availability and
presentation of NKX101 clinical data; plans and timelines for the
continued and future clinical development and commercial potential
of NKX101; and the potential advantages of using
fludarabine/cytarabine (Ara-C) as lymphodepletion for NKX101. These
forward-looking statements are based on current information,
assumptions and expectations that are subject to change and involve
a number of risks and uncertainties that may cause actual results
to differ materially from those contained in the forward-looking
statements.
Interim data from clinical trials are subject to the risk that
one or more of the clinical outcomes may materially change as
patient enrollment continues and more data on existing patients
become available. The clinical trial program is ongoing, and the
final results may be materially different from those reflected in
any interim data we report. Further, others, including regulatory
agencies, may not accept or agree with Nkarta’s assumptions,
estimates, calculations, conclusions or analyses or may interpret
or weigh the importance of data differently, which could impact the
value of the particular program, the approvability or
commercialization of the particular product candidate or product
and the value of the company in general. In addition, the
information Nkarta chooses to publicly disclose regarding a
particular study or clinical trial is typically a summary of
extensive information, and you or others may not agree with what
Nkarta determines is the material or otherwise appropriate
information to include in Nkarta’s disclosure, and any information
Nkarta determines not to disclose may ultimately be deemed
significant with respect to future decisions, conclusions, views,
activities or otherwise regarding a particular product, product
candidate or business.
These and other risks and uncertainties are described more fully
in Nkarta’s filings with the Securities and Exchange Commission
(“SEC”), including the “Risk Factors” section of Nkarta’s Quarterly
Report on Form 10-Q for the quarter ended March 30, 2023, filed
with the SEC on May 11, 2023, and Nkarta’s other documents
subsequently filed with or furnished to the SEC. All
forward-looking statements contained in this press release speak
only as of the date on which they were made. Except to the extent
required by law, Nkarta undertakes no obligation to update such
statements to reflect events that occur or circumstances that exist
after the date on which they were made.
Nkarta Media/Investor Contact:Greg MannNkarta,
Inc.gmann@nkartatx.com
Nkarta (NASDAQ:NKTX)
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