– Relapse-free/progression-free survival for
NKTR-255 plus CD19-22 CAR-T cell therapy at 12 months was
double that of historical controls (67% vs 38%) –
– Eight of nine patients achieved complete
remission, all without detectable MRD –
SAN
FRANCISCO, Oct. 17, 2024 /PRNewswire/ -- Nektar
Therapeutics (Nasdaq: NKTR) today announced the publication of the
first clinical data from a Phase 1 study evaluating NKTR-255 in
combination with an autologous bispecific chimeric antigen receptor
(CAR)-T cell therapy targeting CD19 and CD22 in patients with
relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL)
in Blood, the peer-reviewed medical journal of the American
Society of Hematology.
NKTR-255 is a novel IL-15 receptor agonist currently being
studied in clinical trials in combination with cellular therapies
and immune checkpoint inhibitors. NKTR-255 has shown in previous
clinical studies that it can proliferate a range of immune cells
and augment lymphocyte trafficking.1,2
The data published in Blood showed favorable efficacy
with eight out of nine patients (89%) whom successfully received
CAR19-22 followed by NKTR-255 achieving measurable residual disease
(MRD) negative remission. The study further demonstrated that, at
12 months, relapse-free/progression-free survival for NKTR-255 in
combination with the CD19-22 CAR-T cell therapy was double that of
historical controls (67% vs 38%).
"We are encouraged by these first clinical data that clearly
demonstrate the ability of NKTR-255 to potentiate CAR-T cell
therapy," said Mary Tagliaferri, MD,
Senior Vice President and Chief Medical Officer at Nektar. "Data
showed NKTR-255 in combination with CD19-22 CAR-T cell therapy
resulted in a 67% 12-month relapse-free survival rate in relapsed
or refractory B-ALL and investigators observed significant
increases in proinflammatory cytokines and chemokines which suggest
lymphocyte trafficking to tissues."
The Phase 1 single-center, single-arm dose-escalation study was
conducted by Stanford Medicine and evaluated NKTR-255 in
combination with CD19-22 CAR-T cell therapy in patients with
relapsed or refractory B-ALL (NCT03233854).
"While CAR-T cell therapies have transformed the treatment
landscape for B-cell malignancies, there remains a significant
unmet need to drive durable treatment outcomes as relapse occurs in
the majority of patients," said David
Miklos, MD, Chief of BMT and Cell Therapy Program at
Stanford Medicine, Division of Blood and Marrow Transplantation and
Cellular Therapy.
The primary outcomes of this study were feasibility and
safety. Secondary endpoints were assessed for patients who
received NKTR-255 (n=9) and included pharmacokinetics of NKTR-255
as measured by IL-15 levels in blood and efficacy as measured by
remission free survival (RFS). Exploratory endpoints included
cytokine profiling, CAR19-22 expansion in blood, bone marrow, and
cerebrospinal fluid (CSF), and long-term CAR-T persistence.
Key findings are summarized below:
- No dose-limiting toxicities related to NKTR-255 were
observed. The most common adverse events in patients receiving
NKTR-255 in combination with the CD19-22 CAR-T cell therapy were
fevers, chills, and myelosuppression, which were either
self-limiting or manageable with supportive care. The toxicities
observed with the combination treatment were similar to those seen
after CD19-22 CAR-T cell therapy alone.
- Cytokine and chemokine profiling showed significant increases
in IL-15 levels. Increase in CXCL9 and CXCL10 were associated with
decreases in absolute lymphocyte counts and CD8+ CAR T-cells
in blood, and ten-fold increases CAR-T cells in CSF, suggesting
lymphocyte trafficking to tissue.
- Favorable efficacy was observed in patients with relapsed or
refractory B-ALL treated with NKTR-255 in combination with
CD19-22 CAR-T. Eight out of nine patients achieved complete
remission with or without hematologic recovery, all without
detectable MRD.
- Compared to Stanford's control
group previously treated with the CD19-22 CAR-T cell therapy,
NKTR-255 when added to the cell therapy increased the 12-month
relapse free survival from 38% to 67%. The median RFS for the CAR T
cell only cohort was 3.9 months. For the cohort treated with
NKTR-255 and the CD 19-22 CAR-T cell therapy, the median
RFS has not been reached with over 14 months of follow up.
Only three patients who received combination therapy (33%)
relapsed, suggesting administration of NKTR-255 to the
CD19-22 CAR-T cell therapy helps prevent early disease
recurrence.
The full citation of this article can be accessed here (Volume
144, Issue 16, Pages 1649-1753).
About NKTR-255
NKTR-255 is a biologic that targets the IL-15 pathway in order
to activate the body's innate and adaptive immunity. Through
optimal engagement of the IL-15 receptor complex, NKTR-255 is
designed to enhance functional NK cell populations and formation of
long-term immunological memory, which may lead to sustained and
durable anti-tumor immune response.
In addition to studies in combination with CAR T cell therapies,
NKTR-255 is being studied in a Phase 1 clinical trial sponsored by
AbelZeta Pharma, Inc., which is evaluating C-TIL051, a
tumor-infiltrating lymphocyte therapy, in anti-PD1 resistant
metastatic non-small cell lung cancer (NCT05676749). The JAVELIN
Bladder Medley study (NCT05327530), sponsored by Merck KGaA,
is also ongoing to evaluate NKTR-255 in combination with avelumab
as a maintenance treatment in patients with locally advanced or
metastatic urothelial carcinoma.(NCT05327530)
About Nektar Therapeutics
Nektar Therapeutics is a clinical-stage biotechnology
company focused on developing treatments that address the
underlying immunological dysfunction in autoimmune and chronic
inflammatory diseases. Nektar's lead product candidate,
rezpegaldesleukin (REZPEG, or NKTR-358), is a novel, first-in-class
regulatory T cell stimulator being evaluated in two Phase
2b clinical trials, one in atopic
dermatitis and one in alopecia areata. Our pipeline also includes a
preclinical candidate NKTR-0165, which is a bivalent tumor necrosis
factor receptor type II agonist antibody. Nektar, together with
various partners, is also evaluating NKTR-255, an investigational
IL-15 receptor agonist designed to boost the immune system's
natural ability to fight cancer, in several ongoing clinical
trials. Nektar is headquartered in San
Francisco, California. For further information,
visit www.nektar.com and follow us on LinkedIn.
Cautionary Note Regarding Forward-Looking
Statements
This press release contains forward-looking statements which can
be identified by words such as: "will," "expect," "develop,"
"potential," "advance," "anticipate," "can," and similar references
to future periods. Examples of forward-looking statements include,
among others, statements regarding the therapeutic potential of,
and future development plans for, NKTR-255. 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) our statements regarding the therapeutic potential of NKTR-255
are based on preclinical and clinical findings and observations and
are subject to change as research and development continue; (ii)
NKTR-255 is an investigational agent and continued research and
development for this drug candidate is subject to substantial
risks, including negative safety and efficacy findings in future
clinical studies (notwithstanding positive findings in earlier
preclinical and clinical studies); (iii) NKTR-255 is in clinical
development, and the risk of failure is high and can unexpectedly
occur at any stage prior to regulatory approval; (iv) the timing of
the commencement or end of clinical trials 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, competitive
factors, or delay or failure in ultimately obtaining regulatory
approval in one or more important markets; (v) 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 (vi)
certain other important risks and uncertainties set forth in our
Quarterly Report on Form 10-Q filed with the Securities and
Exchange Commission on August 9,
2024. 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:
Vivian Wu of Nektar
Therapeutics
628-895-0661
For Media:
David Rosen of Argot Partners
(212) 600-1902
david.rosen@argotpartners.com
- Hirayama A. et al. Pharmacodynamic Analysis of CAR-T Cell
Persistence in Patients with Hematologic Malignancies Treated with
NKTR-255, an IL-15 Receptor Agonist That Enhances
CD8 + T-Cells: Preliminary Results from a
Phase 1 Study. Poster presented at: 63rd ASH Annual
Meeting; Dec 11-13, 2021;
Atlanta, GA
- Altan M. et al. NKTR-255+cetuximab in patients with solid
tumors: interim safety and efficacy results from the phase
1b dose-escalation study. Poster
presented at: SITC 2021; Nov 10-14,
2021; Washington, D.C.
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