Juno Therapeutics, Inc. (NASDAQ: JUNO), a biopharmaceutical company
developing innovative cellular immunotherapies for the treatment of
cancer, today presented data from the TRANSCEND trial of JCAR017 in
relapsed and refractory (r/r) aggressive B cell non-Hodgkin lymphoma
(NHL) at the 2017 International Conference on Malignant Lymphoma in
JCAR017 is Juno’s investigative chimeric antigen receptor (CAR) T cell
product candidate that targets CD19, a protein expressed on the surface
of almost all B cell malignancies, and uses a defined composition of CD4
to CD8 T cells and a 4-1BB costimulatory domain, which differentiates it
from other current CD19-directed CAR T product candidates. JCAR017 has
been granted Breakthrough Therapy designation by the FDA for treatment
of r/r aggressive large B cell NHL and PRIME designation by the European
Medicines Agency for treatment of r/r diffuse large B cell lymphoma
(DLBCL), a type of NHL.
“We are pleased to again present TRANSCEND data, which show compelling
results in the treatment of aggressive relapsed or refractory NHL,”
said Sunil Agarwal, M.D., Juno’s President of Research and Development.
“High rates of durable responses and the early survival data are
especially exciting, as is the emerging safety profile. The majority of
TRANSCEND patients experienced no cytokine release syndrome or
neurotoxicity at all. While still early, these data suggest that JCAR017
could be administered on an outpatient basis.”
Data were presented by Jeremy Abramson, M.D., of Massachusetts General
Hospital Cancer Center, from the multicenter TRANSCEND trial (ABSTRACT
#128), a Phase 1 study that has treated a total of 67 patients with r/r
aggressive B cell NHL, including those with DLBCL or follicular lymphoma
grade 3B, as of a data cutoff date of May 4, 2017.
TRANSCEND NHL 001 is a dose-finding study of JCAR017, which is
administered following fludarabine/cyclophosphamide lymphodepletion.
Patients received one of two dose levels (50 or 100 million cells). They
were then evaluated for pharmacokinetics, disease response, and safety
outcomes, including common CAR T side effects such as cytokine release
syndrome (CRS) and neurotoxicity (NT).
Notably, the TRANSCEND NHL 001 protocol includes patients with forms of
B cell NHL that would exclude them from trials of other CAR T product
candidates, including those with ECOG 2 performance status, central
nervous system (CNS) involvement of their lymphoma, and those relapsed
after allogeneic bone marrow transplant.
Data for the DLBCL cohort were presented in two groups: core and full.
The core analysis group (N=44) includes patients that represent the
population that Juno plans to move forward into a pivotal trial in the
second half of 2017. The core group includes patients with DLBCL (de
novo and transformed from follicular lymphoma) that are ECOG Performance
Status 0-1. The full analysis group includes all r/r patients in the
DLBCL cohort (N=55), including 11 patients with poor performance status
or niche subtypes of aggressive NHL. Both the core and full groups
received conforming product, with at least one month follow-up, and with
a data cutoff date of May 4, 2017, for this presentation.
“CAR T cell therapy represents an important step forward in providing
options for these highly chemotherapy refractory patients and addresses
a significant unmet medical need,” said Dr. Abramson. “I am particularly
excited about the emerging efficacy and safety profile with JCAR017,
which could ultimately prove to be optimal therapy for patients with
relapsed and refractory DLBCL.”
Key data and findings:
Core Group (N=44)
Combining data across dose levels:
Overall response rate (ORR) is 86% (38/44) and the complete
response (CR) is 59% (26/44).
Three-month ORR is 66% (21/32) and CR is 50% (16/32). Of patients
in response at three months, 90% (9/10) continue in response at
- Overall response rate (ORR) is 86% (38/44) and the complete
Early data suggest a dose response relationship at three months:
Dose level 1 (50 million cells) ORR is 58% (11/19) and CR is 42%
Dose level 2 (100 million cells) ORR is 78% (7/9) and CR is 56%
- Dose level 1 (50 million cells) ORR is 58% (11/19) and CR is 42%
97% (37/38) of responding patients are alive and in follow-up as
of May 4, 2017.
- 2% (1/44) experienced severe CRS and 18% (8/44) experienced severe NT.
66% (29/44) did not experience any CRS or NT. No deaths were reported
from CRS or NT.
There was one Grade 5 adverse event of diffuse alveolar damage, which
the investigator assessed as possibly related to fludarabine,
cyclophosphamide, and JCAR017 treatment, occurring on day 23 in an
82-year-old subject who refused mechanical ventilation for progressive
respiratory failure while neutropenic on growth factors and broad
spectrum antibiotics and antifungals. This patient had no CRS and
Grade 3 neurotoxicity resolution before the Grade 5 event.
Full Dataset (N=55)
Combining data across dose levels:
- Best ORR is 76% (41/54) and CR is 52% (28/54).
- Three-month ORR is 51% (21/41) and CR is 39% (16/41).
2% (1/55) experienced severe CRS and 16% (9/55) experienced severe NT.
60% (33/55) did not experience any CRS or NT. No deaths reported from
CRS or NT.
Early data do not suggest a dose toxicity relationship at the doses
Severe CRS rate is 3% (1/30) at dose level 1 and 0% (0/19) at dose
Severe NT rate is 20% (6/30) at dose level 1 and 11% (2/19) at
dose level 2.
- Severe CRS rate is 3% (1/30) at dose level 1 and 0% (0/19) at dose
- 11% (6/55) received tocilizumab and 24% (13/55) received dexamethasone.
The most frequently reported treatment-emergent adverse events were
neutropenia (35%), CRS (35%), and fatigue (31%).
Product was available for 98% (86/88) of patients apheresed. TRANSCEND
patients receive product made at JuMP, Juno’s manufacturing facility in
Bothell, Washington. Juno expects commercial production will be
accomplished in less than 21 days, and Juno is investing in
manufacturing infrastructure to enable a smooth prescribing experience
with a reliable delivery time at market entry.
About Juno’s Chimeric Antigen Receptor (CAR) and T Cell Receptor
Juno’s CAR and TCR technologies genetically engineer T cells to
recognize and kill cancer cells. Juno’s CAR T cell technology inserts a
gene for a particular CAR into the T cell, enabling it to recognize
cancer cells based on the expression of a specific protein located on
the cell surface. Juno’s 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. When either type of engineered T
cell engages the target protein on the cancer cell, it initiates a
cell-killing response against the cancer cell. JCAR014 and JCAR017 are
investigational product candidates and their safety and efficacy have
not been established.
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 solid tumors. 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 was
developed in collaboration with SCRI and others.
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.
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,
clinical trial results and the implications thereof, the potential for
outpatient administration of JCAR017, clinical trial plans, future
benefits to patients, projected commercial production time, Juno’s
ability to enable a smooth prescribing experience with a reliable
delivery time at market entry, 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;
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 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 Biotechnology (Shanghai) Co., Ltd., over which Juno
does not exercise complete control, for the development and
commercialization of product candidates in China; and 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 May 4,
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