Safety profile consistent with known toxicities
of CAR T therapies
CAR T persistence observed in 8/10 evaluable
responders at Month 6 and 2/2 evaluable responders at Month 18
bluebird bio, Inc. (Nasdaq: BLUE) and
Bristol-Myers Squibb (NYSE: BMY) announced updated safety and
efficacy results from the ongoing Phase 1 study (CRB-402) of
bb21217, an investigational BCMA-targeted chimeric antigen receptor
(CAR) T cell therapy being studied in patients with
relapsed/refractory multiple myeloma (R/RMM). The data were
presented at the 61st American Society of Hematology (ASH) Annual
Meeting and Exposition in Orlando, Florida.
bb21217 is an investigational BCMA-targeted CAR T cell therapy
that uses the idecabtagene vicleucel (ide-cel; bb2121) CAR molecule
and is cultured with the PI3 kinase inhibitor (bb007) to enrich for
T cells displaying a memory-like phenotype with the intention to
increase the in vivo persistence of CAR T cells.
“Early data from the CRB-402 study in heavily pre-treated
patients (median of six prior lines) with relapsed/refractory
multiple myeloma demonstrate the potential for durable responses
following bb21217 CAR T cell treatment, with a median duration of
response of 11.1 months at the 150 x 106 CAR+ T cell dose level,”
said David Davidson, M.D., chief medical officer, bluebird bio.
“Consistent with the hypothesis underlying the bb21217 program that
memory-like phenotype T cells may survive longer in vivo, we have
observed durable CAR T cell persistence in evaluable patients
(n=2/2) with ongoing response at up to 18 months following
treatment. We are continuing to recruit additional patients in the
study and performing ongoing assessments of the functional
persistence of bb21217, as well as its potential correlation to
durability of response.”
CRB-402, the first in-human study of bb21217 in patients with
R/RMM, is designed to assess the primary endpoint of safety as well
as other pre-defined endpoints including efficacy and
pharmacokinetics measurements. CRB-402 is a two-part, open-label,
multi-site Phase 1 study of bb21217 in adults with R/RMM with a
projected final enrollment of 74 patients. The dose escalation part
of CRB-402 is complete, and the dose expansion part of the study is
ongoing.
“The data of CRB-402 provide additional support that targeting
BCMA with a CAR T therapy could be beneficial in treating
relapsed/refractory multiple myeloma, particularly for heavily
pre-treated patients,” said Kristen Hege, M.D., Senior Vice
President, Hematology/Oncology and Cell Therapy, Early Clinical
Development for Bristol-Myers Squibb. “We have observed durable
responses with bb21217 in this study and look forward to further
results.”
“One of the challenges in treating patients with
relapsed/refractory multiple myeloma is that they often become
resistant to currently available therapies and response durations
generally shorten with each subsequent therapy,” said presenting
author Jesus G. Berdeja, M.D., Sarah Cannon Center for Blood
Cancers, Nashville, Tennessee. “In this heavily-treated patient
population, we are encouraged by the results with bb21217 treatment
in this ongoing study.”
As of the September 4, 2019 cutoff date, data include results
for 38 treated patients. Twenty-four patients received bb21217 in
the dose escalation cohort at three dose levels (12 at 150 x 106
CAR+ T cells; six at 300 x 106 CAR+ T cells; and six at 450 x 106
CAR+ T cells). Fourteen additional patients received bb21217 in the
dose expansion cohort at two dose levels (8 at 300 x 106 CAR+ T
cells and 6 at 450 x 106 CAR+ T cells). The patients had a median
of six prior lines of therapy (min – max; 3 – 17 lines) and 82% had
at least one prior autologous stem cell transplant. High-risk
cytogenetics were reported in 34% of patients and 95% of patients
received prior treatment with an anti-CD38 antibody. All patients
treated in CRB-402 (n=38) had previously received at least three
prior lines of therapy, including an immunomodulatory agent and
proteasome inhibitor. The enrollment criteria for the dose
expansion cohort required all enrolled patients (n=14) to be
refractory to their last prior line of therapy and have previously
received an anti-CD38 antibody.
Safety Results As of the data cutoff, the adverse events
observed with bb21217 were consistent with known toxicities of CAR
T therapies, regardless of dose level.
Of the 38 treated patients, the most common Grade 3/4 toxicities
include neutropenia (82%), leukopenia (55%), thrombocytopenia
(55%), anemia (50%), lymphopenia (34%), hypophosphatemia (21%),
hyponatremia (13%) and febrile neutropenia (11%). Grade 3/4
infections were reported in seven patients (18%).
Twenty-five of 38 patients (66%) developed bb21217-related
cytokine release syndrome (CRS); 12 Grade 1, 11 Grade 2, one Grade
3 and one Grade 5 (death). The fatal CRS event occurred at the 450
x 106 CAR+ T cells dose level, after 15 days of follow-up. Nine of
38 (24%) patients developed neurotoxicity; three Grade 1, three
Grade 2, two Grade 3 (one with vertigo/dizziness and one with
encephalopathy) and one Grade 4 (encephalopathy, previously
reported). For the one patient previously reported with Grade 4
neurotoxicity, Grade 3 CRS was also reported, and both have
resolved.
Efficacy Results As of the data cutoff, 33 of the 38
patients were evaluable for clinical response as defined per the
International Myeloma Working Group Uniform Response Criteria for
multiple myeloma.
Twelve patients were evaluable in the 150 x 106 CAR+ T cells
cohort, with a median follow-up of 17.6 months (min – max; 12 – 23
months). Ten of 12 (83%) evaluable patients (defined as treated
patients with ≥ two months of response data or progressive
disease/death/lost to follow-up within <=2 months) in the 150 x
106 CAR+ T cells cohort demonstrated clinical response, including
four with a stringent complete response (sCR) or complete response
(CR), and six with a very good partial response (VGPR). Among the
ten confirmed responders, the median duration of response was 11.1
months (95% Confidence Interval (CI); 3.3 – not estimable).
As of the data cutoff, follow-up within the two higher dose
cohorts (300 x 106 and 450 x 106 CAR+ T cells) remains early and
none of the confirmed responders have experienced disease
progression. In the 300 x 106 CAR+ T cells cohort, 14 patients were
evaluable for response and six of the 14 (43%) evaluable patients
demonstrated clinical response, including four with a VGPR and two
with a partial response (PR), with a median follow-up of four
months (min – max; 2 – 10 months). In the 450 x 106 CAR+ T cells
cohort, seven patients were evaluable for response and four of the
seven (57%) evaluable patients demonstrated clinical response,
including one with a sCR, two with a VGPR and one with a PR, with a
median follow-up of 3.3 months (min – max; <1 – 6 months).
Evidence of myeloma in the bone marrow, known as minimal
residual disease (MRD), was undetectable by next-generation
sequencing at a sensitivity level of 10-5 in 94% (n=16/17) of all
confirmed responders who had evaluable bone marrow samples
(patients with > PR and
> 1 valid post-baseline MRD
assessment).
As of the data cutoff, CAR T cell persistence was observed in
eight of ten patients with ongoing response and evaluable at six
months, and two out of two patients with ongoing response and
evaluable at 18 months.
The dose expansion part of the CRB-402 study is ongoing to
further recruit patients and explore bb21217 at the 450 x 106 CAR+
T cells dose cohort, assess functional persistence of bb21217 and
durability of response.
About bb21217 for Multiple Myeloma bb21217 is an
investigational BCMA-targeted CAR T cell therapy that uses the
ide-cel CAR molecule and is cultured with the PI3 kinase inhibitor
(bb007) to enrich for T cells displaying a memory-like phenotype
with the intention to increase the in vivo persistence of CAR T
cells bb21217 is being developed in partnership between bluebird
bio and Bristol-Myers Squibb.
The clinical development program for bb21217 includes the
ongoing Phase 1 CRB-402 study. CRB-402 is the first-in-human study
of bb21217 in patients with R/RMM, designed to assess safety,
pharmacokinetics, efficacy and duration of effect. CRB-402 is a
two-part (completed dose escalation and ongoing dose expansion),
open-label, multi-site Phase 1 study of bb21217 in adults with
R/RMM with a projected final enrollment of 74 patients. For more
information visit: clinicaltrials.gov using identifier
NCT03274219.
bb21217 is not approved for any indication in any geography.
About Multiple Myeloma Multiple myeloma is a cancer of
certain cells in the blood, called plasma cells. The cause of
multiple myeloma is not known, and currently there is no cure.
However, there are a number of treatment options available that can
lead to response. For some people with multiple myeloma, response
can last many years. Patients who have already been treated with
some available therapies but continue to have progression of their
disease have “relapsed” and “refractory” multiple myeloma, meaning
their cancer has reoccurred after they have received initial
treatments. Patients with relapsed and refractory multiple myeloma
have fewer treatment options.
About bluebird bio, Inc. bluebird bio is pioneering gene
therapy with purpose. From our Cambridge, Mass., headquarters,
we’re developing gene therapies for severe genetic diseases and
cancer, with the goal that people facing potentially fatal
conditions with limited treatment options can live their lives
fully. Beyond our labs, we’re working to positively disrupt the
healthcare system to create access, transparency and education so
that gene therapy can become available to all those who can
benefit.
bluebird bio is a human company powered by human stories. We’re
putting our care and expertise to work across a spectrum of
disorders including cerebral adrenoleukodystrophy, sickle cell
disease, β-thalassemia and multiple myeloma, using three gene
therapy technologies: gene addition, cell therapy and
(megaTAL-enabled) gene editing.
bluebird bio has additional nests in Seattle, Wash.; Durham,
N.C.; and Zug, Switzerland. For more information, visit
bluebirdbio.com.
Follow bluebird bio on social media: @bluebirdbio,
LinkedIn, Instagram and YouTube.
bluebird bio is a trademark of bluebird bio, Inc.
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 us on LinkedIn, Twitter,
YouTube, Facebook and Instagram.
Bristol-Myers Squibb: Advancing Cancer Research At
Bristol-Myers Squibb, patients are at the center of everything we
do. The goal of our cancer research is to increase quality,
long-term survival and make cure a possibility. We harness our deep
scientific experience, cutting-edge technologies and discovery
platforms to discover, develop and deliver novel treatments for
patients.
Building upon our transformative work and legacy in hematology
and Immuno-Oncology that has changed survival expectations for many
cancers, our researchers are advancing a deep and diverse pipeline
across multiple modalities. In the field of immune cell therapy,
this includes registrational chimeric antigen receptor (CAR) T-cell
agents for numerous diseases, and a growing early-stage pipeline
that expands cell and gene therapy targets, and technologies. We
are developing cancer treatments directed at key biological
pathways using our protein homeostasis platform, a research
capability that has been the basis of our approved therapies for
multiple myeloma and several promising compounds in early to
mid-stage development. Our scientists are targeting different
immune system pathways to address interactions between tumors, the
microenvironment and the immune system to further expand upon the
progress we have made and help more patients respond to treatment.
Combining these approaches is key to delivering new options for the
treatment of cancer and addressing the growing issue of resistance
to immunotherapy. We source innovation internally, and in
collaboration with academia, government, advocacy groups and
biotechnology companies, to help make the promise of
transformational medicines a reality for patients.
Bristol-Myers Squibb Cautionary
Statement Regarding Forward-Looking Statements This
press release contains “forward-looking statements” within the
meaning of the Private Securities Litigation Reform Act of 1995
regarding, among other things, the research, development and
commercialization of pharmaceutical products. All statements that
are not statements of historical facts are, or may be deemed to be,
forward-looking statements. Such forward-looking statements are
based on historical performance and current expectations and
projections about our future financial results, goals, plans and
objectives and involve inherent risks, assumptions and
uncertainties, including internal or external factors that could
delay, divert or change any of them in the next several years, that
are difficult to predict, may be beyond our control and could cause
our future financial results, goals, plans and objectives to differ
materially from those expressed in, or implied by, the statements.
These risks, assumptions, uncertainties and other factors include,
among others, that future study results will be consistent with the
results to date, that bb21217 may not achieve its primary study
endpoints or receive regulatory approval for the indication
described in this release in the currently anticipated timeline or
at all and, if approved, whether such product candidate for such
indication described in this release will be commercially
successful. No forward-looking statement can be guaranteed.
Forward-looking statements in this press release should be
evaluated together with the many risks and uncertainties that
affect Bristol-Myers Squibb’s business and market, particularly
those identified in the cautionary statement and risk factors
discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for
the year ended December 31, 2018, as updated by our subsequent
Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and
other filings with the Securities and Exchange Commission. The
forward-looking statements included in this document are made only
as of the date of this document and except as otherwise required by
applicable law, Bristol-Myers Squibb undertakes no obligation to
publicly update or revise any forward-looking statement, whether as
a result of new information, future events, changed circumstances
or otherwise.
Bluebird bio Cautionary Statement
Regarding Forward-Looking Statements This press release
contains “forward-looking statements” within the meaning of the
Private Securities Litigation Reform Act of 1995 regarding, among
other things, the research, development and commercialization of
pharmaceutical products. All statements that are not statements of
historical facts are, or may be deemed to be, forward-looking
statements. Such forward-looking statements are based on historical
performance and current expectations and projections about our
future financial results, goals, plans and objectives and involve
inherent risks, assumptions and uncertainties, including internal
or external factors that could delay, divert or change any of them
in the next several years, that are difficult to predict, may be
beyond our control and could cause our future financial results,
goals, plans and objectives to differ materially from those
expressed in, or implied by, the statements. These risks,
assumptions, uncertainties and other factors include, among others,
that future study results will be consistent with the results to
date, that bb21217 may not achieve its primary study endpoints or
receive regulatory approval for the indication described in this
release in the currently anticipated timeline or at all and, if
approved, whether such product candidate for such indication
described in this release will be commercially successful, and that
the collaboration with Bristol-Myers Squibb may not continue or be
successful. No forward-looking statement can be guaranteed.
Forward-looking statements in this press release should be
evaluated together with the many risks and uncertainties that
affect bluebird bio’s business, particularly those identified in
the risk factors discussion in bluebird bio’s Annual Report on Form
10-K for the year ended December 31, 2018, as updated by our
subsequent Quarterly Reports on Form 10-Q, Current Reports on Form
8-K and other filings with the Securities and Exchange Commission.
The forward-looking statements included in this document are made
only as of the date of this document and except as otherwise
required by applicable law, bluebird bio undertakes no obligation
to publicly update or revise any forward-looking statement, whether
as a result of new information, future events, changed
circumstances or otherwise.
Hyperlinks are provided as a convenience and for informational
purposes only. Neither Bristol-Myers Squibb nor bluebird bio bears
responsibility for the security or content of external websites or
websites outside of their respective control.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20191209005754/en/
For Bristol-Myers Squibb Investors: Tim Power, 609-252-7509
Timothy.Power@bms.com
or
Media: Rose Weldon, 609-252-3345 Rose.Weldon@bms.com
media@bms.com
For bluebird bio Investors: Elizabeth Pingpank, 617-914-8736
epingpank@bluebirdbio.com
or
Media: Victoria von Rinteln, 617-914-8774
vvonrinteln@bluebirdbio.com
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