NantKwest Announces Launch of Merkel Cell Carcinoma Phase II Trial Deploying Novel Triple Combination of off-the-Shelf Natural Killer haNKⓇ Cell Therapy with Superagonist IL-15 Cytokine Therapy and PD-L1 Checkpoint Inhibitor Therapy
( 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
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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