Study Tests Elimination Of Chemotherapy And
Expands Upon Previous Combination Study Of NK Cell Therapy With
N-803 Showing Promising Clinically Meaningful Responses In Merkel
Cell Carcinoma Patients
NantKwest Inc. (Nasdaq:NK), a leading, clinical-stage, natural
killer cell based therapeutics company, today announced the launch
of a novel triple combination, phase II clinical trial in Merkel
cell carcinoma (MCC).
NantKwest’s phase II immunotherapy trial builds upon the
company’s earlier phase II single-combination study using its
proprietary, off-the-shelf aNKTM natural killer cell therapy and
IL-15/Fc superagonist (N-803), which produced an objective
responses in 3 of 7 patients.
In this new clinical trial, patients will be dosed with: (i) the
novel chemotherapy-free combination of our haNK cell therapy, which
are aNK cells that are genetically engineered to express the
high-affinity variant of the CD16 receptor (V158 FcγRIIIa), (ii)
avelumab, a PD-L1 targeting checkpoint inhibitor, and (iii) N-803,
a superagonist IL-15/Fc cytokine therapy, in a regimen designed to
synergistically optimize the therapeutic potential of each
agent.
Commenting on the initiation of this novel triple combination
trial in MCC, Patrick Soon-Shiong, MD, Chairman and CEO of
NantKwest said, “Even in a heavily pretreated patient population,
including patients who have failed checkpoint inhibitor therapy, we
were encouraged to see our combination of aNK cell and N-803
therapy exhibit preliminary clinically meaningful antitumor
activity, including objective response in this resistant
setting.”
Dr. Soon-Shiong continued, “Building upon this human clinical
trial data, we are pleased to announce the transition of this
earlier study to include haNK cell therapy in combination with the
IL-15 superagonist N-803 and the PD-L1 checkpoint inhibitor
avelumab, which we believe, when used together, will offer
synergies and the potential to improve response rates for patients
with MCC that may also potentially translate to a number of
additional solid tumor indications.”
In preclinical and human clinical studies conducted by
NantKwest, the combination of haNK cells with a number of different
therapeutic antibodies, including avelumab, led to enhanced tumor
cell killing when compared to the use of the antibody alone. The
IL-15/Fc superagonist N-803, developed by NantCell, Inc., an
affiliate company, has been shown to synergistically activate NK
and T cells and enhance cancer cell killing in both single agent
and combination therapy. The PD-L1 checkpoint inhibitor avelumab, a
monoclonal antibody developed by Merck KGaA and approved in 2017 by
the FDA, targets the programmed death-ligand 1 protein (PD-L1),
commonly expressed on a wide range of cancer cells. Avelumab works
by blocking PD-L1 from binding PD-1 receptors on T-cells, resulting
in an increase in CD8+ T-cell immune responses. This effect is
amplified with the addition of N-803 and haNK cells.
With encouraging preclinical and clinical responses already
demonstrated for aNK as a single agent therapy or in combination,
we believe this existing dataset provides validation for our novel,
triple combination clinical trial design.
MCC is a rare and aggressive skin cancer that arises from
uncontrolled growth of cells in the skin. Increasing in incidence,
approximately 2,500 new cases are reported in the U.S. each year.
Patients with metastatic or locally advanced MCC have an extremely
poor prognosis, with less than 20% of patients surviving longer
than five years. Typically these patients are treated with a range
of drugs, including chemotherapy, which can result in significant
side effects. Although new immune therapies have the potential to
improve survival, MCC is still fatal for a majority patients who
have progressed on or after treatment with a checkpoint inhibitor
and represents an unmet medical need.
Study Design
The Phase II clinical study will evaluate a combination therapy
with our off-the-shelf CD16-targeted natural killer cells (haNK),
the IL-15 superagonist (N-803), and avelumab, without the use of
cytotoxic chemotherapy, in subjects with MCC that have progressed
on or after treatment with a checkpoint inhibitor. The combination
of these agents have been safely studied in our previous clinical
trials for other solid cancer indications. The goal of combining
these therapies is to synergistically maximize the killing of
cancer cells while attempting to spare patients from chemotherapy
and its associated adverse side effects.
haNK Cell Therapy Platform
NantKwest’s haNK cell therapy platform is a natural killer cell
therapy that was developed to optimize the key role of natural
killer cells in mediating innate immunity, enhancing adaptive
immune responses, and, specifically in the case of haNK, improve
anti-tumor responses via antibody-dependent cell-mediated
cytotoxicity (ADCC). ADCC is an important component of the human
immune system associated with the synergistic interaction of
natural killer cells with antibodies to directly kill a target cell
that has been identified by an antigen-specific antibody. ADCC
represents one of the key mechanisms that antibodies utilize to
target and kill cancer cells. Engineered to express the
high-affinity variant of the CD16, high affinity Fc receptor (V158
FcγRIIIa), in preclinical studies, the combination of haNK cells
with a number of different therapeutic antibodies led to enhanced
tumor cell killing when compared to the use of the antibody as a
single therapeutic agent, providing strong support for this novel
combination immunotherapeutic approach.
N-803 Superagonist IL-15 Cytokine Therapy
Interleukin-15 (IL-15) is a critical factor controlling the
development, proliferation and activation of effector natural
killer (NK) cells and CD8+ memory T cells. In preclinical and
clinical studies, this cytokine has exhibited potent antitumor
activities against well-established tumors. N-803, developed by
NantCell, an affiliate company, is a novel IL-15 superagonist
complex consisting of an IL-15 mutant (IL-15N72D) bound to an IL-15
receptor α/IgG1 Fc fusion protein. In preclinical and clinical
studies, N-803 has shown improved biological activity, longer
persistence in lymphoid tissues and enhanced anti-tumor activity by
simultaneously mobilizing both the innate and adaptive arms of the
immune system. This robust immunostimulatory capacity is believe to
elicit rapid and durable responses against cancer cells compared to
native, non-complexed IL-15 in vivo.
For additional information regarding this MCC clinical trial
please visit, www.clinicaltrials.gov and for additional information
on NantKwest, please visit www.nantkwest.com
About NantKwest
NantKwest is an innovative clinical-stage immunotherapy company
focused on harnessing the power of the innate immune system by
using the natural killer cell to treat cancer, infectious diseases
and inflammatory diseases.
NantKwest is uniquely positioned to implement precision cancer
medicine, with the potential to change the current paradigm of
cancer care. Natural Killer cells are ancient cells in the human
body designed to recognize and detect cells under stress or
infected. The NantKwest “off-the-shelf” activated Natural Killer
(NK) platform is designed to destroy cancer and virally infected
cells from the body. The safety of our NK cells as well as their
activity against a broad range of cancers have been tested in
multiple phase 1 clinical trials in the United States, Canada and
Europe. In addition to our NK cells capability to be administered
in the outpatient setting as an “off-the-shelf” living drug, it
serves as a universal cell-based therapy without need for
individualized patient matching. Moreover, our NK cell based
platform has been bioengineered to incorporate chimeric antigen
receptors (CARs) and antibody receptors to potentially further
optimize targeting and potency in the therapeutic disease.
With the capacity to grow active killer cells as a biological
cancer therapy, NantKwest’s NK cells have been designed to induce
cell death against cancers and virally infected cells by multiple
modes of action that include: Direct killing via innate recognition
in which NK cells release toxic granules directly into the target
(diseased) cell through cell-to-cell contact; Antibody-mediated
killing using haNKs, which are NK cells engineered to incorporate a
high binding affinity receptor that binds to an administered
antibody, enhancing the cancer cell killing effect of that
antibody; Chimeric Antigen Receptor directed killing using the
taNK® platform, which includes NK cells engineered to incorporate
chimeric antigen receptors (CARs) to target tumor-specific antigens
found on the surface of cancer cells. All three modes of killing
(innate, antibody-mediated, and Chimeric Antigen Receptor directed
killing) using the t-haNK™ platform, which is an innovative
combination of our haNK® and taNK® platforms in a single cell.
Our haNK®, taNK®, and t-haNK™ platforms have been designed to
address certain limitations of T-cell therapies including the
reduction of risk of serious “cytokine storms.” As an
“off-the-shelf” therapy, NantKwest’s NK cells do not rely on a
patient’s own often compromised immune system. In Phase 1 clinical
trials in patients with late stage cancer, Nantkwest’s NK cells
have been administered as an investigational outpatient infusion
therapy without any reported severe side effects to date, even at
doses of 10 billion cells.
By leveraging an integrated and extensive genomics and
transcriptomics discovery and development engine, together with a
pipeline of multiple, clinical-stage, immuno-oncology programs, we
believe NantKwest is uniquely positioned to be the premier
immunotherapy company and transform medicine by delivering living
drugs in a bag and bringing novel NK cell-based therapies to
routine clinical care.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. Forward-looking statements include statements concerning or
implying NantKwest will be successful in improving the treatment of
cancer. Risks and uncertainties related to this endeavor include,
but are not limited to, obtaining FDA approval of our NK cells as
well as other therapeutics as part of the NANT Cancer Vaccine
platform as a cancer treatment.
Forward-looking statements are based on management's current
expectations and are subject to various risks and uncertainties
that could cause actual results to differ materially and adversely
from those expressed or implied by such forward-looking statements.
Accordingly, these forward-looking statements do not constitute
guarantees of future performance, and you are cautioned not to
place undue reliance on these forward-looking statements.
These and other risks regarding our business are described in
detail in our Securities and Exchange Commission filings, including
in our Quarterly Report on Form 10-Q for the quarter ended
September 30, 2018. These forward-looking statements speak only as
of the date hereof, and we disclaim any obligation to update these
statements except as may be required by law.
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Jen Hodson562-397-3639Jen@nant.com
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