SAN FRANCISCO, Nov. 9, 2016 /PRNewswire/ -- Nektar
Therapeutics (Nasdaq: NKTR) today announced that new Phase 1
clinical data for Nektar's lead immuno-oncology agent, NKTR-214,
were presented at the SITC 2016 Annual Meeting. NKTR-214 is
an investigational immuno-stimulatory therapy designed to expand
specific cancer-fighting T cells and Natural Killer (NK) cell
abundance directly in the tumor micro-environment and increase
expression of PD-1 on these immune cells. The results were
presented by Adi Diab, MD, Assistant
Professor, Department of Melanoma Medical Oncology, Division of
Cancer Medicine, The University of
Texas MD Anderson Cancer Center in an oral presentation
during today's session entitled "New Cancer Immunotherapy Agents in
Development."
Interim results presented were from the ongoing Phase 1
dose-escalation, first-in-human, trial of single-agent NKTR-214 in
patients with locally advanced or metastatic solid tumors,
including melanoma, renal cell carcinoma (RCC), bladder, colorectal
and other solid tumor cancers. A total of 20 patients were
treated in four separate every three-week (q3w) dose cohorts
(ranging from 0.003 mg/kg q3w to 0.012 mg/kg q3w) with 18 of these
patients evaluable for anti-tumor activity. Based upon
encouraging anti-tumor activity and tolerability of NKTR-214
observed at the 0.006 mg/kg q3w dose, an every two week (q2w)
cohort of the 0.006 mg/kg dose began enrolling in September 2016 with an additional 5 patients
enrolled to this cohort, all of which are continuing on
therapy.
"NKTR-214 resulted in robust activation of the immune system and
encouraging anti-tumor activity, including a partial response
observed in a patient who continues to be treated with NKTR-214,"
said Dr. Ivan Gergel, Senior Vice
President, Drug Development & Chief Medical Officer of
Nektar. "NKTR-214 was also well tolerated in patients when
administered as an every two-week or every three-week outpatient
therapy. We are very encouraged by the clinical profile emerging
for NKTR-214 and the totality of the data from this ongoing
single-agent trial of NKTR-214."
Preliminary encouraging evidence of anti-tumor activity has been
observed to date in the ongoing study:
- 12/18 (72%) evaluable patients had stable disease at the
initial 8 week scan
- 7/18 (39%) evaluable patients had radiographic reductions in
tumor size per RECIST 1.1 on NKTR-214
- One patient with metastatic melanoma (prior treatment with
ipilimumab and a BRAF inhibitor) has received 13 cycles of
treatment (0.003 mg/kg q3w) with stable disease and continues on
therapy with NKTR-214
- In the 18 evaluable patients, a total of 5 patients with
metastatic RCC who had progressed on 1 prior tyrosine kinase
inhibitor (TKI) were treated with NKTR-214 at the 0.006 mg/kg q3w
dose level:
- 1/5 (20%) of these RCC patients had a uPR per RECIST 1.1 (at 16
week scan) and treatment with NKTR-214 is ongoing
- 2/5 of these RCC patients had additional tumor reductions of 6%
and 10% per RECIST 1.1 while on NKTR-214
NKTR-214 also demonstrated a favorable safety and tolerability
profile with convenient, outpatient q2w or q3w administration in 25
patients evaluable for safety to-date:
- No immune-related AEs were observed (e.g. colitis, dermatitis,
hepatitis pneumonitis, adrenal insufficiency)
- No deaths or grade 4 AEs related to NKTR-214
- No capillary leak syndrome was observed at any dose
- One patient experienced a dose-limiting toxicity (DLT) of
hypotension/syncope at 0.012 mg/kg q3w and continued on treatment
at 0.006 mg/kg q3w
- 3/25 patients experienced grade 3 hypotension, which was
rapidly reversed with fluid administration and all patients
continued on treatment with NKTR-214
- Most common grade 1-2 adverse events were fatigue, pruritis,
cough, decreased appetite, pyrexia, and hypotension
Immune pheno-typing was conducted and biomarkers of immune
activation were measured in patients with evaluable tumor biopsies
and blood samples. Treatment with NKTR-214 produced a robust
elevation in immune cell frequency and activation, including:
- Increase in total and newly proliferating (Ki67+) CD4+ T cells,
CD8+ T cells, and Natural Killer (NK) cells in 9/9 patients with
blood samples evaluated in the trial to-date, with increases of up
to 30-fold observed
- Increase in frequency of PD-1+ T cell subsets of up to 9-fold
in the blood
- Increase in CD8+ T cells and Natural Killer (NK) cells of up to
10-fold in the tumor micro-environment in patients with evaluable
tumor biopsies (pre-dose and post-dose at week 3), with minimal
intratumoral changes to T regulatory cells
- Increase in expression of cell-surface PD-1 on T cell subsets
of up to 2-fold in the tumor micro-environment
- Induction of an activation gene signature in the tumor
micro-environment, including increases of 5-fold or greater in
expression of interferon γ, perforin and granzyme B genes
- Changes in T cell repertoire (TCR), which is a measure of T
cell clonality, in the tumor micro-environment
"We are extremely pleased with the single-agent activity of
NKTR-214 and the potential of NKTR-214 to transform the
immuno-oncology landscape," said Howard W.
Robin, President & CEO of Nektar Therapeutics. "As
the first I-O agent to demonstrate that it can increase
tumor-infiltrating lymphocytes (TILs) and increase PD-1 expression
on immune cells in humans, NKTR-214 complements not only existing
checkpoint inhibitors, such as nivolumab, but also other I-O
mechanisms in development."
In September 2016, Nektar entered
into a clinical collaboration with Bristol-Myers Squibb to evaluate
NKTR-214 as a potential combination treatment regimen with
Bristol-Myers Squibb's Opdivo (nivolumab) in five
tumor types and seven potential indications. The Phase 1/2 clinical
trials will enroll up to 260 patients and will evaluate the
potential for the combination of Opdivo (nivolumab) and
NKTR-214 to show improved and sustained efficacy and tolerability
above the current standard of care in melanoma, kidney,
triple-negative breast cancer, bladder and non-small cell lung
cancer patients. The initial dose-escalation trial is
underway with Opdivo (nivolumab) and NKTR-214.
NKTR-214 is an experimental therapy designed to stimulate
cancer-killing immune cells in the body by targeting CD122 specific
receptors found on the surface of these immune cells, known as CD8+
effector T cells and Natural Killer (NK) cells. In preclinical
studies, treatment with NKTR-214 resulted in a rapid expansion of
these cells and mobilization into the tumor
micro-environment.1 NKTR-214 has an antibody-like
dosing regimen similar to the existing checkpoint inhibitor class
of approved medicines. A Phase 1/2 clinical study is ongoing to
evaluate single-agent NKTR-214 in cancer patients.
About Nektar
Nektar Therapeutics has a robust R&D pipeline and
portfolio of approved partnered medicines in oncology, pain,
immunology and other therapeutic areas. In the area of
oncology, Nektar is developing NKTR-214, an
immuno-stimulatory CD122-biased agonist, that is in Phase 1/2
clinical development for patients with solid tumors. ONZEALD™
(etirinotecan pegol), a long-acting topoisomerase I inhibitor, is
being developed for patients with advanced breast cancer and brain
metastases and is partnered with Daiichi Sankyo in Europe. In
the area of pain, Nektar has an exclusive worldwide
license agreement with AstraZeneca for MOVANTIK™ (naloxegol), the
first FDA-approved once-daily oral peripherally-acting
mu-opioid receptor antagonist (PAMORA) medication for the treatment
of opioid-induced constipation (OIC), in adult patients with
chronic, non-cancer pain. The product is also approved in
the European Union as MOVENTIG® (naloxegol) and is
indicated for adult patients with OIC who have had an inadequate
response to laxatives. The AstraZeneca agreement also includes
NKTR-119, an earlier stage development program that is a
co-formulation of MOVANTIK and an opioid. NKTR-181, a wholly owned
mu-opioid analgesic molecule for chronic pain conditions, is in
Phase 3 development. In hemophilia, Nektar has a
collaboration agreement with Baxalta for ADYNOVATE™ [Antihemophilic
Factor (Recombinant)], a longer-acting PEGylated Factor VIII
therapeutic approved in the U.S. and Japan for
patients over 12 with hemophilia A. In anti-infectives, the company
has two collaborations with Bayer Healthcare, Cipro Inhale in
Phase 3 for non-cystic fibrosis bronchiectasis and Amikacin Inhale
in Phase 3 for patients with Gram-negative pneumonia.
Nektar's technology has enabled nine approved products in
the U.S. or Europe through partnerships with
leading biopharmaceutical companies, including AstraZeneca's
MOVANTIK™, Baxalta's ADYNOVATE™, UCB's Cimzia® for Crohn's disease
and rheumatoid arthritis, and Amgen's Neulasta® for
neutropenia.
Nektar is headquartered in San
Francisco, California, with additional operations
in Huntsville, Alabama and Hyderabad, India.
Further information about the company and its drug development
programs and capabilities may be found online
at http://www.nektar.com.
MOVANTIK™ is a trademark and MOVENTIG® is a registered trademark
of the AstraZeneca group of companies. ADYNOVATE™ is a
trademark of Baxalta Inc.
ONZEALD™ is a trademark of Nektar Therapeutics.
Cimzia® is a trademark of UCB.
Opdivo is a registered trademark of Bristol-Myers
Squibb.
Cautionary Note Regarding Forward-Looking
Statements
This press release contains forward-looking statements which can
be identified by words such as: "anticipate," "intend," "plan,"
"expect," "believe," "should," "may," "will" and similar references
to future periods. Examples of forward-looking statements include,
among others, statements we make regarding the potential
therapeutic benefit of NKTR-214 for cancer patients, the future
clinical development plans for NKTR-214, the potential of NKTR-214
in combination with other immunotherapy agents including
Bristol-Myers Squibb's Opdivo (nivolumab), and certain other
statements regarding the prospects and potential of Nektar's
business, technology platform and drug candidate
pipeline. . Forward-looking statements are
neither historical facts nor assurances of future performance.
Instead, they are based only on our current beliefs, expectations
and assumptions regarding the future of our business, future plans
and strategies, anticipated events and trends, the economy and
other future conditions. Because forward-looking statements relate
to the future, they are subject to inherent uncertainties, risks
and changes in circumstances that are difficult to predict and many
of which are outside of our control. Our actual results may differ
materially from those indicated in the forward-looking statements.
Therefore, you should not rely on any of these forward-looking
statements. Important factors that could cause our actual results
to differ materially from those indicated in the forward-looking
statements include, among others: (i) NKTR-214 is in early
stage clinical development and the risk of failure remains high and
failure can unexpectedly occur at any stage for one or more of the
cancer indications being studied prior to regulatory approval due
to lack of sufficient efficacy, safety considerations or other
factors that impact drug development; (ii) data reported from the
Phase 1 Trial is interim data only and the final results will
change based on continuing observations from patients that
currently remain enrolled in the trial (e.g., whether unconfirmed
objective responses ultimately become confirmed responses) and
additional patients to be enrolled in the trial; (iii) the Phase 1
Trial results for NKTR-214 remain subject to final data gathering
and analysis review and confirmation procedures; (iv) the timing or
success of the start or end of clinical trials such as those
planned for NKTR-214 may be delayed or unsuccessful due to
regulatory delays, clinical trial design issues, slower than
anticipated patient enrollment, drug manufacturing challenges,
changing standards of care, and clinical outcomes; (v) scientific
discovery of new medical breakthroughs is an inherently uncertain
process and the future success of the application of Nektar's
technology platform to potential new drug candidates such as
NKTR-214 is therefore very uncertain and unpredictable and one or
more research and development programs could fail; (vi) Nektar's
patent applications for NKTR-214 may not issue in one or more
jurisdictions, patents that have issued may not be enforceable, or
additional intellectual property licenses from third parties may be
required in the future; (vii) the outcome of any existing or future
intellectual property or other litigation related to Nektar's
proprietary product candidates, including, without limitation,
NKTR-214, is unpredictable and could have a material adverse effect
on our business; and (viii) certain other important risks and
uncertainties set forth in Nektar's Quarterly Report on Form 10-Q
for the quarter ended September 30,
2016 filed with the Securities and Exchange Commission on
November 4, 2016. Any
forward-looking statement made by us in this press release is based
only on information currently available to us and speaks only as of
the date on which it is made. We undertake no obligation to update
any forward-looking statement, whether written or oral, that may be
made from time to time, whether as a result of new information,
future developments or otherwise.
Contact:
For Investors:
Jennifer Ruddock of Nektar
Therapeutics
415-482-5585
Jodi Sievers of Nektar
Therapeutics
415-482-5593
For Media:
Dan Budwick of Pure Communications,
Inc.
973-271-6085
dan@purecommunicationsinc.com
1. Charych, D., et al., Clin Cancer
Res.; 22 (3) 2016
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