Juno Therapeutics, Inc. announced today that clinical data from its most
advanced chimeric antigen receptor (CAR) product candidates, JCAR017,
JCAR015 and JCAR014, demonstrated encouraging evidence of clinical
responses in acute lymphoblastic leukemia (ALL) and non-Hodgkin’s
lymphoma (NHL). Clinical results were presented in oral and poster
presentations at the 56th American Society of Hematology
(ASH) Annual Meeting in San Francisco, California.
Highlights from the research include:
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High rates of tumor reduction in B-cell malignancies, including
complete remission rate of 89% in adult relapsed/refractory B-cell ALL
with JCAR015.
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Robust T cell expansion and persistence and clinical remissions with
JCAR017.
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Potential for prolonged T cell persistence with WT-1, a high-affinity
T cell receptor (TCR) candidate, in acute myeloid leukemia (AML).
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Association of cell expansion and persistence with clinical outcome.
“The tumor response rates and duration observed in these ongoing studies
remain encouraging as we advance our lead product candidates in
hematological malignancies,” said Juno CEO, Hans Bishop.
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In an oral presentation on the Phase I clinical trial results of
JCAR015 in adults with ALL, Jae H. Park, M.D. of the Leukemia
Service, Department of Medicine, Memorial Sloan Kettering Cancer
Center, in New York City, presented:
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• Complete remission occurred in 24/27 (89%) evaluable patients and
complete molecular remission occurred in 21/24 (88%) evaluable
patients with relapsed/refractory adult ALL.
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• In this ongoing trial, median overall survival was 8.5 months.
Durable responses were observed in patients with and without
subsequent allogeneic stem cell transplant.
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• Cytokine release syndrome (CRS) requiring vasopressors and/or
mechanical ventilation was required for 5/15 patients with
morphologic disease, or greater than 5% blasts in the bone marrow,
and 0/13 patients without morphologic disease. Grade 3/4
neurotoxicity occurred in 7/28 patients and was generally reversible.
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In an oral presentation on the Phase I clinical trials results of
JCAR015 in patients with B-cell NHL, Craig S. Sauter, M.D., of the
Department of Medicine, Memorial Sloan Kettering Cancer Center,
presented:
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• At a median follow-up of 9 months (range 1-17.5), 6/6 (100%)
patients with poor-risk, relapsed/refractory aggressive B cell NHL
remain alive and in remission after treatment with high dose
chemotherapy and autologous stem cell transplantation, followed by
CD19-directed CAR T cell therapy. Two patients remain alive more
than one year from treatment.
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• One patient treated with 1 x107 CAR T/kg experienced
severe CRS.
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3.
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In a poster presentation on the Phase I clinical trials results of
JCAR017 in pediatric patients with ALL, Rebecca A. Gardner, M.D.,
of Ben Towne Center for Childhood Cancer Research, Seattle
Children's Research Institute, in Seattle, presented:
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• Eleven of 13 (85%) patients with relapsed/refractory ALL following
allogeneic stem cell transplantation obtained or maintained an MRD
negative complete remission following CAR T cell therapy.
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• All 11 responding patients exhibited in vivo expansion of CAR T
cells (median peak CAR+ T cells of 478/uL [range 63-1288] occurring
7‐14 days post infusion), with 6/8 (75.0%) of evaluable patients
having CAR T cell persistence of more than 40 days.
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• Two patients received treatment with steroids and tocilizumab for
severe cytokine release syndrome. One of these patients experienced
grade 4 encephalopathy and there was an additional patient that
experienced grade 3 encephalopathy.
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In an oral presentation on the Phase I clinical trials results of
JCAR014 in patients with relapsed/refractory ALL, NHL and chronic
lymphocytic leukemia (CLL), Cameron J. Turtle, MBBS, Ph.D., of the
Clinical Research Division, Fred Hutchinson Cancer Research Center,
in Seattle, presented:
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• In patients receiving defined composition products, responses were
observed in 6/10 (60%) evaluable NHL patients, and 2/2 evaluable CLL
patients, complete remission occurred in 11/11 (100%) patients and
complete molecular remissions occurred in 9/11 (82%) patients with
ALL.
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• A subset of NHL patients tested in whom CAR‐T cells became
undetectable developed a T cell immune response to sequences in the
murine CD19‐specific single-chain variable fragment (scFv) component
of the CAR transgene.
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• Severe CRS was observed in 3/13 (23%) ALL patients, including one
death, and in 0/14 evaluable NHL/CLL patients. Grade 3 delirium was
observed in one patient with CLL.
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5.
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In a poster presentation on the Phase I/II clinical trial results of
WT-1 in post-transplant patients with AML, Merav Bar, M.D., of the
Fred Hutchinson Cancer Research Center, presented:
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• Escalating doses of donor-derived virus specific CD8+ T cells
transduced to express a high-affinity TCR specific for the HLA
A*02:01-restricted WT1126-134 (RMFPNAPYL) epitope were administered
in high-risk AML patients after allogeneic hematopoietic stem cell
transplantation.
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• WT-1 specific T cell delivery was generally well tolerated.
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• 13/15 patients remain alive with follow-up for up to 18 months.
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• 12/15 have ongoing detectable WT-1 cells with follow up ranging
from 5 to 368 days from the last infusion.
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About Juno’s Chimeric Antigen Receptor and High-affinity T Cell
Receptor Platform
Juno is developing cell-based immunotherapies based on its chimeric
antigen receptor, or CAR, and high-affinity T cell receptor, or TCR,
platform to genetically engineer T cells to recognize and kill cancer
cells. T cells are a type of white blood cells that identify and kill
infected or abnormal cells, including cancer cells, in healthy
individuals. Juno leverages its CAR and TCR platform to activate a
patient’s own T cells so that they attack cancer cells. Through genetic
engineering, a gene is inserted for a particular CAR or TCR construct
into the T cell enabling it to better recognize cancer cells. The CAR
technology directs T cells to recognize cancer cells based on the
expression of specific proteins located on the cell surface, whereas the
TCR technology provides the T cells with a specific T cell receptor to
recognize protein fragments derived from either the surface or inside
the cell. CAR constructs typically use a single chain variable fragment,
or scFv, to recognize a protein of interest. The modified T cells can be
infused into the patient or frozen and stored for later infusion.
About Juno
Juno Therapeutics, Inc. is building a fully integrated biopharmaceutical
company focused on revolutionizing medicine by re-engaging the body’s
immune system to treat cancer. Founded on the vision that the use of
human cells as therapeutic entities will drive one of the next important
phases in medicine, Juno is developing cell-based cancer immunotherapies
based on chimeric antigen receptor and high-affinity T cell receptor
technologies to genetically engineer T cells to recognize and kill
cancer. Juno is developing multiple cell-based product candidates to
treat a variety of B-cell malignancies as well as solid tumors. Several
product candidates have shown compelling evidence of tumor shrinkage in
the clinical trials in refractory leukemia and lymphoma conducted to
date. The company’s long-term aim is to improve and leverage its
cell-based platform to develop new product candidates that address a
broader range of cancers and human diseases. Juno brings together
innovative technologies from some of the world’s leading research
institutions, including the Fred Hutchinson Cancer Research Center,
Memorial Sloan Kettering Cancer Center, and Seattle Children’s Research
Institute.
www.JunoTherapeutics.com
Forward Looking Statements
This press release contains forward-looking statements, including
statements regarding the clinical development of our product candidates,
the safety and efficacy of our product candidates as well as their
potential, and the encouraging nature of clinical data observed to date.
Forward-looking statements are subject to risks and uncertainties that
could cause actual results to differ materially and reported results
should not be considered as an indication of future performance. These
risks and uncertainties include, but are not limited to: risks
associated with the success, cost and timing of our product development
activities and clinical trials; the approval and commercialization of
our product candidates; and risks of increased regulatory requirements,
amongst others. These forward-looking statements speak only as of the
date hereof. Juno Therapeutics disclaims any obligation to update these
forward-looking statements.
Copyright Business Wire 2014