—Updated JCAR017 (liso-cel) data in core group
at dose level 2 showed 74% (14/19) ORR and 68% (13/19) CR rate at 3
months, with 50% (7/14) CR at 6 months—
—JCAR017 data continue to support better
responses at dose level 2 without increased toxicity observed for
CRS and NT compared to dose level 1 in core group—
Juno Therapeutics, Inc. (NASDAQ: JUNO), a biopharmaceutical
company developing innovative cellular immunotherapies for the
treatment of cancer, today highlighted presentations and data
from the 59th American Society of Hematology (ASH) Annual Meeting
and Exposition in Atlanta, Georgia, December 9-12, 2017.
“Juno presented a wide range of data and new insights at ASH,
including updated data in the TRANSCEND trial,” said Hans Bishop,
Juno’s President and CEO. “Using a defined composition of cells at
a precise dose, we have been able to gain critical insights into
important potential associations that may contribute to JCAR017’s
efficacy and tolerability profile that we believe has the potential
to be best in class. We are confident that the investments we’ve
made in our defined composition, scientific, and translational
capabilities will allow us to better characterize and improve
current and future CAR T products and product candidates for
patients.”
During ASH, Juno also announced that JCAR017 had received the
United States Adopted Name (USAN) lisocabtagene maraleucel
(liso-cel).
Updated Data from TRANSCEND Trial of JCAR017
Data from the TRANSCEND study of JCAR017 (liso-cel) in patients
with relapsed or refractory (r/r) aggressive B-cell non-Hodgkin
lymphoma (NHL) were presented in an oral session by Dr. Jeremy
Abramson, M.D. of Massachusetts General Hospital on Monday,
December 11. JCAR017 is a defined composition CD19-directed CAR T
cell product candidate using a 4-1BB costimulatory domain.
Data were based on a cutoff date of October 9, 2017 and add to
those disclosed on November 1, 2017 in Abstract #581. The core
group includes patients with Diffuse Large B-Cell Lymphoma (DLBCL;
NOS and transformed from follicular lymphoma) who are ECOG
Performance Status 0-1. The full analysis group represents all r/r
patients in the DLBCL cohort, which includes patients with
poor performance status (ECOG Performance Status 2) or with niche
subtypes of aggressive NHL.
Enrollment of the pivotal cohort is ongoing with the core group
at dose level 2, one of multiple previously evaluated doses.
Key results:
- In the core group at dose level 2
(DL2=100 million cells), the data showed a 3 month overall response
rate (ORR) of 74% (14/19) and a 3 month complete response (CR) rate
of 68% (13/19). Of patients that have reached 6 months of
follow-up, 50% (7/14) were in CR. Across doses, 80% (16/20) of
patients in core group with CR at 3 months stayed in CR at 6
months, and 92% (11/12) of patients in response at 6 months
remained in response as of the data cutoff date.
- In the core group, 1% (1/67)
experienced severe cytokine release syndrome and 15% (10/67)
experienced severe neurotoxicity. 58% (39/67) had no CRS or NT of
any grade.
- In the full group, 1% (1/91)
experienced severe CRS and 12% (11/91) experienced severe NT. 60%
(55/91) had no CRS or NT of any grade.
- The most common treatment-emergent
adverse events (TEAEs) other than CRS and NT that occurred at ≥25%
in the full group included neutropenia (49%), anemia (38%), fatigue
(37%), thrombocytopenia (29%), nausea (27%), and diarrhea (25%).
The most common TEAEs were similar between core and full
groups.
Juno believes JCAR017’s safety profile could enable outpatient
administration. A biologics license application filing is expected
to be completed in the second half of 2018, with approval as early
as the end of 2018.
Oral Presentations on JCAR017 Translational Insights
Two additional oral presentations reported new clinical
correlates, and safety and efficacy insights associated with
JCAR017.
On Saturday, December 9, Tanya Siddiqui, M.D., of City of Hope
National Medical Center, presented exploratory analyses from
Abstract #193 suggesting that patient factors independent of
JCAR017 may impact safety and efficacy for DLBCL patients. These
factors included:
- Baseline patient characteristics,
including high tumor burden and markers of inflammation, were
associated with high CAR T cell expansion and increased rates of
CRS and NT.
- Data showed an approximately 8-fold
increased risk for CRS and NT in patients with high baseline tumor
burden.
- Baseline markers of inflammation were
associated with more durable responses; with respect to tumor
burden the association was less pronounced.
On the same day, Howard Stern, M.D., Ph.D., of Juno presented
data from ASH Abstract #194, examining JCAR017 infiltration into
tumor tissue and exploring potential mechanisms of resistance and
relapse. Findings included:
- JCAR017 cells infiltrated tumors, and
more infiltration trended with better response. At disease
progression, tumors tended to express CD19 and lack CAR T
cells.
- In patients whose disease progressed,
no single resistance pathway appeared to be upregulated in the
tumor at the time of progression, but well-known pathways such as
PD-L1 and IDO were upregulated in different patients, suggesting
that combinations with other immunotherapies may be
beneficial.
Potential for Outpatient Administration of JCAR017
On Saturday, December 9, David Maloney, M.D., Ph.D. of Fred
Hutchinson Cancer Research Center presented Poster #1552,
highlighting preliminary data on the potential for outpatient
administration of JCAR017 in patients with r/r DLBCL. The safety
profile of JCAR017, including low rates of all grade and severe CRS
and NT, supports evaluation of outpatient administration.
8 patients had received JCAR017 as an outpatient at multiple
trial sites and were evaluable with 28 or more days post-infusion.
Compared to inpatient administration, outpatient administration
showed an approximate 40% reduction in hospital days. 88% (7/8) of
patients remained outpatient for at least 3 days post CAR T
administration.
The goal of JCAR017 outpatient administration is to increase
access and reduce hospitalization days without impacting safety.
Juno anticipates generating additional data to evaluate this
potential both as part of the TRANSCEND trial and in additional
studies.
Pharmacodynamics of JCAR017
In a presentation on Sunday, December 10, Mark Heipel presented
Poster #2835, highlighting pharmacodynamics and blood analytes with
clinical response to JACR017 in patients with r/r DLBCL. The
presentation showed that JCAR017 CAR T cells expanded in the blood
and bone marrow of all patients, but at different rates between
patients and different NHL histologies.
Furthermore, an increase in CD8+ cell expansion was observed at
dose level two compared to dose level one. Preliminary modeling
suggests a potential therapeutic window for CAR T expansion may
exist that limits toxicity and optimizes for durable response.
Findings suggested that patient factors and tumor characteristics,
apart from JCAR017 itself, are important to expansion and thus
potentially response.
Manufacturing of JCAR017
In a poster presentation on Monday, December 11, Christopher G.
Ramsborg, Ph.D., highlighted the product and process controls in
manufacturing that enable the defined composition of JCAR017,
including the delivery of precise doses of CD4+ and CD8+ CAR T
cells. Three aspects of JCAR017 manufacturing and process control
strategy contribute to low between-drug product lot
variability:
- A precise, consistent flat dose of
administered CD4+ and CD8+ CAR T cells within +/- 8% of target cell
count.
- Control and optimization of CD4+ and
CD8+ T cell culture conditions that result in low between-drug
product lot variability of phenotypes (e.g., CCR7) and in vitro
function (e.g., IL-2, TNF-α and IFN-γ production after antigen
stimulation).
- Constant formulation and volume of drug
product that contributes to consistent cell health.
Controls result in a commercial manufacturing process expected
to be successful >95% with a consistent turnaround time <21
days.
Multiple Myeloma Presentations
Poster presentations showing preclinical data highlighted early,
encouraging insights into the design of BCMA-directed CAR T cells.
Juno plans to present additional data on its BCMA program and
strategy next year. The presentations at ASH highlighted Juno’s
fully human binder, and showed that the inhibition of TGFβ
signaling and combination strategies with Lenalidomide may
contribute to a potential best-in-class product for multiple
myeloma.
About Juno
Juno Therapeutics is building a fully integrated
biopharmaceutical company focused on developing innovative cellular
immunotherapies for the treatment of 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 multiple solid tumors and
multiple myeloma. Several product candidates have shown compelling
clinical responses in clinical trials in refractory leukemia and
lymphoma conducted to date. Juno’s long-term aim is to 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, Seattle
Children’s Research Institute (SCRI), the University
of California, San Francisco, and The National
Cancer Institute. Juno Therapeutics has an exclusive
license to the St. Jude Children’s Research Hospital patented
technology for CD19-directed product candidates that use 4-1BB,
which was developed by Dario Campana, Chihaya Imai, and
St. Jude Children’s Research Hospital. Juno’s product
candidate JCAR017 (lisocabtagene maraleucel; liso-cel) was
developed in collaboration with SCRI and others. JCAR017 is an
investigational CART T therapy and is not approved for use in any
country.
About The Juno-Celgene Collaboration
Celgene Corporation and Juno Therapeutics formed a collaboration
in June 2015 under which the two companies will leverage T cell
therapeutic strategies to develop treatments for patients with
cancer and autoimmune diseases with an initial focus on chimeric
antigen receptor (CAR) and T cell receptor (TCR) technologies. In
April 2016, Celgene exercised its option to develop and
commercialize the Juno CD19 program outside North America and
China.
Forward-Looking Statements
This press release contains “forward-looking statements” within
the meaning of the Private Securities Litigation Reform Act of
1995, Section 27A of the Securities Act of 1933, and Section 21E of
the Securities Exchange Act of 1934, including statements regarding
Juno’s mission, progress, and business plans; clinical or
translational data and the implications thereof; the timing of
regulatory submissions or approvals; clinical trial plans; the
potential best-in-class profile for JCAR017 (liso-cel); the
potential for outpatient administration of JCAR017; Juno’s ability
to harness its investments to better characterize and improve
current and future CAR T products and product candidates for
patients; the importance of controlling product composition;
expected success rates and turnaround time for manufacturing; the
potential of JCARH125 to be a best-in-class product; and the
potential of the Celgene collaboration. Forward-looking statements
are subject to risks and uncertainties that could cause actual
results to differ materially from such forward-looking statements,
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 Juno’s product development activities and clinical
trials; Juno’s ability to obtain regulatory approval for and to
commercialize its product candidates; with respect to the timing of
JCAR017 approval, the time it takes to complete enrollment of the
pivotal cohort, the timing of Juno’s FDA submission, and
the duration of FDA review; Juno’s ability to
establish a commercially-viable manufacturing process and
manufacturing infrastructure; regulatory requirements and
regulatory developments; success of Juno’s competitors with respect
to competing treatments and technologies; Juno’s dependence on
third-party collaborators and other contractors in Juno’s research
and development activities, including for the conduct of clinical
trials and the manufacture of Juno’s product candidates; Juno’s
ability to attract and retain key scientific, quality
control/assurance, manufacturing or management personnel; Juno’s
dependence on Celgene for the development and
commercialization outside of North
America and China of Juno’s CD19 product candidates
and any other product candidates for
which Celgene exercises an option; Juno’s dependence
on JW Therapeutics (Shanghai) Co., Ltd and its affiliates for
the development and commercialization of product candidates
in China; Juno’s ability to obtain, maintain, or protect
intellectual property rights related to its product candidates;
amongst others. For a further description of the risks and
uncertainties that could cause actual results to differ from those
expressed in these forward-looking statements, as well as risks
relating to Juno’s business in general, see Juno’s Quarterly Report
on Form 10-Q filed with the Securities and Exchange
Commission on November 1, 2017 and Juno’s other
periodic reports filed with the Securities and Exchange
Commission. These forward-looking statements speak only as of the
date hereof. Juno disclaims any obligation to update these
forward-looking statements.
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version on businesswire.com: http://www.businesswire.com/news/home/20171212006305/en/
Juno Therapeutics, Inc.Investor Relations:Nicole Keith,
206-566-5521nikki.keith@junotherapeutics.comorMedia:Christopher Williams,
206-566-5660chris.williams@junotherapeutics.com
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