SAN FRANCISCO, Nov. 11, 2020 /PRNewswire/ -- Nektar Therapeutics
(Nasdaq: NKTR) today announced four data presentations for its I-O
pipeline from three separate clinical-stage investigational agents
at the 2020 Society for Immunotherapy of Cancer (SITC) Annual
Meeting.
New clinical results were presented for bempegaldesleukin
(BEMPEG; NKTR-214), NKTR-262 and NKTR-255. Data for BEMPEG and
NKTR-262 were featured in two oral presentation sessions presented
by Adi Diab, MD, Associate Professor, Department of
Melanoma Medical Oncology, Division of Cancer
Medicine, The University of Texas
MD Anderson Cancer Center during, respectively, the Concurrent
Rapid Oral Abstract Presentation Session and the Combinatorial
Therapies Session on Wednesday, November 11th.
Clinical data for NKTR-255 and preclinical data for NKTR-262 were
also featured in poster presentations by Dr. Nina Shah, Associate Professor, Department of
Medicine, at the University of California San
Francisco and Dr. Annah
Rolig, Earle A. Chiles Research Institute, Providence Cancer
Institute on Monday, November
9th.
Adi Diab, MD, lead investigator
of the PIVOT-02 study noted: "These updated PIVOT-02 clinical data
further validate our prior results that BEMPEG plus nivolumab
provides both deep and durable responses in first-line metastatic
Stage IV melanoma patients. We observed a total overall response
rate of 53%, with 34% achieving a complete response, and now we
have also observed a median depth of response of 78.5%, as well as
a median progression free survival for the entire cohort of 30.9
months."
"The data presented at this year's SITC Meeting highlight
that, by targeting key immunological processes, we have the
opportunity to more effectively harness the body's immune system to
fight cancer," said Jonathan Zalevsky, Ph.D., Head of Research
and Development at Nektar Therapeutics. "In the PIVOT-02 study
of BEMPEG plus nivolumab, we observed that 90% or 18 of the 20
metastatic melanoma patients who responded went on to achieve a
100% reduction in their RECIST target lesions, and, importantly for
the first time, we reported a two year survival rate of 77% from
this study, and median OS has not yet been reached."
"For our TLR agonist candidate, we presented data demonstrating
that the combination of NKTR-262 and bempegaldesleukin alters the
tumor micro-environment through activation of both the innate and
adaptive arms of the immune system," continued Zalevsky. "Data
presented for NKTR-255 demonstrated this novel IL-15 agonist was
biologically active in patients. We observed durable and sustained
increases in Natural Killer and CD8+ T cells as well as disease
stabilization in the first patients who were treated in the lowest
dose cohorts, which included patients with highly-refractory and
heavily pre-treated multiple myeloma and Non-Hodgkin's
lymphoma."
Clinical presentations at 2020 SITC are available for
download at
https://www.nektar.com/science/scientific-posters-and-presentations.
Highlights from the presentations are as follows:
Abstract 420: "Progression-free survival and biomarker
correlates of response with BEMPEG plus NIVO in previously
untreated patients with metastatic melanoma: results from the
PIVOT-02 study", Diab, A., et al. (Concurrent
Rapid Oral Abstract Presentation Session: Clinical):
- Confirmed best overall response rate (ORR) was 53% (20/38) in
efficacy-evaluable patients, with a 34% (13/38) complete response
(CR) rate. 47% (18/38) of patients achieved 100% reduction in
RECIST target lesions. 80% (16/20) of patients had ongoing
responses and median duration of response was not reached at a
29-month follow-up. (Response was measured per RECIST 1.1 by
blinded independent central radiology review for
efficacy-evaluable patients treated. Data cut as of
September 1, 2020).
- Median progression-free survival (PFS) observed was 30.9
months. Median overall survival (OS) was not reached. Based upon a
Kaplan-Meier Estimate of OS, the OS rates at 12 months, 24 months
and 36 months are 82%, 77%, and 71%, respectively.
- New biomarker translational data presented show non-invasive,
on-treatment biomarkers (CD8+ PSD* and eosinophils) predicted
response to the combination.
- BEMPEG plus NIVO was well tolerated; treatment-related AEs are
predictable and consistent with previous reports.
- In July of 2019, this novel combination was awarded US FDA
Breakthrough Therapy Designation for the treatment of patients with
previously untreated unresectable or metastatic melanoma.
- In melanoma, registrational Phase 3 trials evaluating BEMPEG
plus NIVO are enrolling patients in the first-line metastatic
setting (PIVOT IO 001; NCT03635983) and in the adjuvant setting
(PIVOT-12; NCT04410445).
Abstract 368: "REVEAL: Phase 1 dose-escalation
study of NKTR-262, a novel TLR7/8 agonist, plus bempegaldesleukin:
local innate immune activation and systemic adaptive immune
expansion for treating solid tumors", Diab, A., et al.
(Combinatorial Therapies):
- Safety, pharmacokinetics (PK), pharmacodynamics (PD) and
biomarker data supported selection of NKTR-262 3.84 mg
Intra-Tumoral (IT) plus BEMPEG 0.006 mg IV q3w as the RP2D. A
maximum-tolerated dose was not reached.
- Robust TLR 7/8 engagement was observed upon administration of
NKTR-262 IT.
- NKTR-262 plus BEMPEG induced systemic activation of T cells and
Natural Killer (NK) cells demonstrating engagement of the entire
immune activation cascade required for systemic tumor
clearance.
- Induction of TLR7/8-responsive genes significantly correlated
with CD11c+ baseline density. CD11c+ target cells
are significantly more abundant in baseline melanoma biopsies
vs other tumor types.
- NKTR-262 IT, as monotherapy or in combination with BEMPEG,
showed early signs of clinical activity and an acceptable safety
profile in a highly relapsed/refractory, heavily pre-treated
melanoma patient population.
Abstract 355: "First-in-human phase I
study of NKTR-255 in patients with relapsed/refractory hematologic
malignancies," Shah, N., et al.
- NKTR-255 was biologically active and demonstrated consistent
expansion of lymphocytes, with durable and sustained increases in
NK and CD8+ T cells in this highly refractory population of
patients with multiple myeloma (MM) and non-Hodgkin lymphoma
(NHL).
- NKTR-255 was well tolerated with low-grade, cytokine-related
AEs that were transient and easily managed.
- NKTR-255 exhibited a long half-life with no evidence of
accumulation.
- These data support continued dose escalation of NKTR-255 and
subsequent evaluation in combination with other anticancer
agents.
Abstract 451: "Combining Bempegaldesleukin
(CD122-preferential IL-2 pathway agonist) and NKTR-262 (TLR7/8
agonist) pairs local innate activation with systemic CD8+ T cell
expansion to enhance anti-tumor immunity", Rolig, A., et
al.
- BEMPEG/NKTR-262 treatment produces a higher fraction of
activated tumor antigen-specific cytotoxic CD8 T cells
systemically, correlating with superior anti-tumor efficacy
relative to BEMPEG combined with radiotherapy (RT).
- BEMPEG/NKTR-262 combination therapy depends on CD8 T cells and
NK cells.
- BEMPEG/NKTR-262 combination therapy induces intra-tumoral CD8+
T cells that have increased activity as demonstrated by increased
granzyme expression and increased tumor killing, and reduced
conversion to an exhausted phenotype (PD-1, Tim3, Lag3).
- Loss of NK cells reduces CD8+T cell percentages and function in
the peripheral blood and in the tumor, suggesting a connection
between early NK cell function and anti-tumor adaptive immune
responses.
Analyst Call with Panel of Oncology Experts:
Nektar will webcast an analyst and investor conference call that
will include SITC authors and presenters, Dr. Adi Diab, Associate Professor, Melanoma Medical
Oncology at The University of Texas MD
Anderson Cancer Center; Dr. Brendan
Curti, Director of the Melanoma Program, Cytokine and
Adoptive Immunotherapy and Genitourinary Oncology Research at
Providence Cancer Institute; Dr. Nina
Shah, Associate Professor, Department of Medicine, at the
University of California San Francisco;
and Dr. Alan Tan, Assistant
Professor, Department of Internal Medicine, Division of Hematology,
Oncology and Cell Therapy at Rush Medical College.
Date and Time: Wednesday, November 11, 2020, at
4:15 p.m. EST
Dial-in: 877-881-2183 (toll-free) or 970-315-0453
(enter access code 2090614)
Investors and analysts can also view slides and listen to the
live audio webcast of the presentation at
https://edge.media-server.com/mmc/p/25u4g5o7. The event will also
be available for replay for two weeks on the company's website,
www.nektar.com.
Dr. Adi Diab
Adi Diab, M.D., serves as
Associate Professor of Melanoma Medical Oncology at The
University of Texas MD Anderson Cancer
Center. Dr. Diab is one of the lead investigators in PIVOT-02, the
Phase 1/2 study of BEMPEG plus nivolumab, and in REVEAL, the Phase
1/2 study of NKTR-262 and BEMPEG. He is also on the steering
committee for the BMS-sponsored Phase 3 registrational study, PIVOT
IO 001, which is ongoing, in patients with previously
untreated metastatic melanoma. His research is focused on
developing new immunotherapeutic strategies that will improve
clinical outcomes in patients. He has authored or co-authored over
thirty scientific publications and abstracts and serves as a
reviewer for Cancer Discovery, Journal of Clinical
Oncology, Nature Reviews Journal of Immunotherapy and
Journal of the American Society of Hematology.
Dr. Brendan D. Curti
Brendan D. Curti, M.D., is the
Robert W. Franz Chair for Clinic Research and Member in the Earle
A. Chiles Research Institute at Providence Cancer Institute. He
serves as the Director of Cytokine and Adoptive Immunotherapy,
Melanoma Program and Genitourinary Oncology Research. His clinical
research focuses on developing new immunotherapies for melanoma,
renal cell carcinoma, prostate cancer and bladder cancer. He
previously served as a Senior Investigator in the Biological
Response Modifiers Program at the National Cancer Institute and was
an Associate Professor at the Penn State
College of Medicine before joining the Earle A. Chiles
Research Institute at Providence Cancer Institute.
Dr. Nina Shah
Nina Shah, M.D., is an Associate
Professor in the Department of Medicine at the University of California San Francisco and a
specialist in blood diseases who focuses on treating multiple
myeloma, a type of cancer affecting certain cells in the bone
marrow. Her areas of professional interest include the intersection
of immunology and oncology as well as helping patients fight
multiple myeloma by boosting their immune systems. She is an
investigator in the NKTR-255 Phase 1/2 study in hematological
malignancies. She belongs to the American Society of Clinical
Oncology, American Society of Hematology and American Society for
Transplantation and Cellular Therapy.
Dr. Alan Tan
Alan Tan, MD, is an Assistant
Professor in the Division of Hematology, Oncology and Cell Therapy
at Rush Medical College. He specializes in kidney cancer, bladder
cancer, prostate cancer and melanoma. He also has an extensive
background in hematologic malignancies. Dr. Tan has clinical
research interest in designing and implementing clinical trials to
test novel immunotherapies and targeted therapies for renal cell
carcinoma and GU malignancies. He is an investigator in the
NKTR-255 Phase 1/2 study in hematological malignancies. He also has
interest in precision genomic cancer medicine, identifying
molecular alterations that will serve as targets for individualized
treatment strategies.
About Bempegaldesleukin (NKTR-214)
Bempegaldesleukin (BEMPEG: NKTR-214) is an investigational
CD122-preferential IL-2–pathway agonist that leverages the
clinically validated IL-2 pathway to stimulate an antitumor immune
response.1 BEMPEG was engineered to deliver a
controlled, sustained, and preferential IL-2 pathway signal, with
the goals of stimulating an antitumor immune response while
minimizing toxicity, thereby allowing for outpatient
administration.1,2 In a phase 1 trial of BEMPEG in
combination with the checkpoint inhibitor nivolumab (NIVO;
PIVOT-02), the combination was well tolerated and produced durable
responses that deepened over time in multiple advanced solid tumor
types.3
In July of 2019, Bristol-Myers
Squibb and Nektar Therapeutics announced that
the U.S. Food and Drug Administration granted
Breakthrough Therapy Designation for investigational agent
bempegaldesleukin in combination with nivolumab for the
treatment of patients with previously untreated unresectable or
metastatic melanoma.
The Nektar-Bristol-Myers Squibb joint clinical development
program for BEMPEG+NIVO includes registrational and other studies
of BEMPEG plus NIVO in select tumor types (melanoma, renal cell
carcinoma or RCC, and bladder cancer). This includes a Phase 3
trial in first-line advanced melanoma (NCT03635983), a Phase 3
trial in adjuvant melanoma (NCT04410445), a Phase 3 trial in
advanced RCC (NCT03729245), a Phase 3 trial in muscle-invasive
bladder cancer (NCT04209114), a Phase 2 trial in
cisplatin-ineligible urothelial carcinoma (NCT03785925) and a Phase
1/2 trial in combination with a tyrosine kinase inhibitor in
advanced RCC (NCT04540705).
BEMPEG is also being evaluated by Nektar in the PROPEL study in
combination with pembrolizumab in non-small cell lung cancer
(NCT03138889) and in collaboration with Vaccibody in the DIRECT-01
study in combination with VB10.NEO in squamous cell carcinoma of
the head and neck (NCT03548467).
About NKTR-255
NKTR-255 is an IL-15 receptor agonist designed to activate the
IL-15 pathway, expand NK cells and promote the survival and
expansion of memory CD8+ T cells. Through optimal engagement of the
IL-15Rα/IL-2Rβγ receptor complex, NKTR-255 enhances formation of
long-term immunological memory, which may lead to sustained
anti-tumor immune response. NKTR-255 is uniquely designed to
overcome the challenges of recombinant IL-15, which is rapidly
cleared from the body and must be administered frequently and in
high doses, limiting its utility due to toxicity and convenience of
use.
About NKTR-262
NKTR-262 is a novel small molecule agonist designed to activate
toll-like receptors (TLRs). Intratumoral delivery of NKTR-262
promotes TLR activation to induce the development of
antigen-specific immunity by initiating the process by which the
immune system generates antigen-specific cytotoxic T cells to the
patient's specific tumor.4 NKTR-214 targets CD122
specific receptors found on the surface of these cancer-killing
immune cells, known as CD8+ effector T cells.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company
whose mission is to discover, develop and deliver innovative
medicines that help patients prevail over serious diseases. For
more information about Bristol-Myers Squibb, visit us
at BMS.com or follow the company on
LinkedIn, Twitter, YouTube, Facebook,
and Instagram.
About Nektar
Nektar Therapeutics is a biopharmaceutical company with a
robust, wholly owned R&D pipeline of investigational medicines
in oncology, immunology and virology as well as a portfolio of
approved partnered medicines. 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.
- Bentebibel S-E, et al. A First-in-Human Study and Biomarker
Analysis of NKTR-214, a Novel IL2Rβγ -Biased Cytokine, in
Patients with Advanced or Metastatic Solid Tumors. Cancer
Discovery 2019;9:711-21.
- Charych D, et al. Modeling the receptor pharmacology,
pharmacokinetics, and pharmacodynamics of NKTR-214, a kinetically
controlled interleukin-2 (IL2) receptor agonist for cancer
immunotherapy. PLoS ONE 2017;12.
- Diab A, et al. Bempegaldesleukin (NKTR-214) plus nivolumab in
patients with advanced solid tumors: Phase 1 dose-escalation study
of safety, efficacy and immune activation (PIVOT-02). Cancer
Discovery 2020
- Adams S. Toll-like receptor agonists in cancer therapy.
Immunotherapy. 2009;1(6):949-964. doi:10.2217/imt.09.70.
*Polynomial Strength Difference (PSD): difference in PSI between
C1D1 and C1D8; PSI, polyfunctional strength index, using IsoPlexis
technology
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements which can
be identified by words such as: "will," "develop," "may," "design"
and similar references to future periods. Examples of
forward-looking statements include, among others, statements we
make regarding the therapeutic potential of bempegaldesleukin in
combination with other agents, and the therapeutic potential of
each of NKTR-255 and NKTR-262, as well as the availability of
results and outcomes from clinical and preclinical studies of our
drug candidates. 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, 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) our statements regarding the therapeutic
potential of our drug candidates are based on preclinical and
clinical findings and the expected therapeutic potential for each
of our drug candidates is subject to change as research and
development continue; (ii) our drug candidates are in clinical
development and the risk of failure remains high and failure can
unexpectedly occur at any stage for one or more of the indications
being studied prior to regulatory approval due to lack of
sufficient efficacy, safety considerations or other factors that
impact drug development; (iii) data reported from ongoing
preclinical and clinical trials are necessarily interim data only
and the final results will change based on continuing observations;
(iv) scientific discovery of new medical breakthroughs is an
inherently uncertain process and the future success of potential
new drug candidates (such as bempegaldesleukin, NKTR-255 and
NKTR-262) is therefore very uncertain and unpredictable; (v) the
timing of the commencement or end of clinical studies and the
availability of clinical data may be delayed or unsuccessful due to
regulatory delays, slower than anticipated patient enrollment,
manufacturing challenges, changing standards of care, evolving
regulatory requirements, clinical trial design, clinical outcomes,
delays caused by our collaboration partners, and enrollment
competition; (vi) patents may not issue from our patent
applications for our drug candidates, patents that have issued may
not be enforceable, or additional intellectual property licenses
from third parties may be required; and (vii) certain other
important risks and uncertainties set forth in Nektar's Quarterly
Report on Form 10-Q filed with the Securities and Exchange
Commission on November 6, 2020. 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:
Jerry
Isaacson of Nektar Therapeutics
628-895-0634
Vivian Wu of Nektar Therapeutics
628-895-0661
For Media:
Dan Budwick of 1AB
dan@1abmedia.com
973-271-6085
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