Data from the pivotal liso-cel TRANSCEND NHL
001 study demonstrate patients with relapsed/refractory large
B-cell lymphomas experienced high rate of durable responses
Generally manageable safety profile with low
incidence of CAR T-related severe cytokine release syndrome (CRS)
and neurologic events
Data presented at 2019 American Society of
Hematology (ASH) Annual Meeting
Bristol-Myers Squibb Company (NYSE: BMY) today announced the
pivotal study of lisocabtagene maraleucel (liso-cel) an
investigational CD19-directed CAR T-cell therapy with a defined
composition of purified CD8+ and CD4+ CAR T cells in
relapsed/refractory large B-cell lymphomas (TRANSCEND NHL 001) met
its primary and secondary endpoints while demonstrating durable
responses. The data were presented during an oral session at the
2019 ASH Annual Meeting in Orlando, Fla.
“Longer-term follow-up from the TRANSCEND study shows that
liso-cel resulted in a rapid, high rate of durable complete
responses with low incidence of severe cytokine release syndrome
and neurologic events in two and ten percent, respectively, among
patients with relapsed/refractory large B-cell lymphomas,” said
Jeremy Abramson, M.D., Associate Professor of Medicine at Harvard
Medical School and Director of the Lymphoma Center at Massachusetts
General Hospital. “Additionally, responses with liso-cel were seen
across patient groups including high-risk patients such as those
with refractory disease, older patients and those with high tumor
burden.”
In the study, 344 patients were leukapheresed and 269 patients
received liso-cel at one of three dose levels (50 x 106 n=51; 100 x
106 n=177; and 150 x 106 n=41). There were 25 patients that
received nonconforming product and there were two instances where
product could not be manufactured. Patients were heavily pretreated
and had aggressive disease with a median of three prior therapies
including 35% with prior autologous or allogeneic hematopoietic
stem cell transplant (HSCT) and 67% with chemotherapy-refractory
disease. Bridging therapy was administered to 59% of patients.
Among patients evaluable for efficacy (n=256), the overall
response rate (ORR) was 73% (187/256, 95% CI: 67 – 78) with 53% of
patients (136/256, 95% CI: 47 – 59) achieving a complete response
(CR). Responses were similar across all patient subgroups. The
median duration of response (DOR) for all patients was not reached
(95% CI: 8.6 months – NR) at a median follow-up of 12 months (95%
CI: 11.2 – 16.7). Median progression-free survival (PFS) was 6.8
months (95% CI: 3.3 – 14.1) and median overall survival (OS) was
21.1 months (95% CI: 13.3 – NR). The median PFS and OS for patients
who achieved a CR was not reached with 65.1% of patients
progression free and 85.5% of patients alive at 12 months,
respectively.
Among all patients, 79% (213/269) had grade 3 or higher
treatment-emergent adverse events (TEAE) including neutropenia
(60%, 161/269), anemia (38%, 101/269) and thrombocytopenia (27%,
72/269). Instances of any grade cytokine release syndrome (CRS)
occurred in 42% (113/269) of patients at a median onset of 5 days
and grade 3 or higher CRS occurring in 2% (6/269) of patients.
There were neurologic events (NEs) that occurred in 30% of patients
(80/269) with grade 3 or higher NEs occurring in 10% (27/269) of
patients at a median onset of 9 days. Nineteen and 21% of patients
received tocilizumab and corticosteroids, respectively. There were
four grade 5 TEAEs related to liso-cel in the study from diffuse
alveolar damage, pulmonary hemorrhage, multiple organ dysfunction
syndrome or cardiomyopathy. There were three grade 5 TEAEs
considered unrelated to liso-cel from fludarabine
leukoencephalopathy, septic shock and progressive multifocal
leukoencephalopathy. Eight patients had ongoing CRS/NE at the time
of death from other reasons. Prolonged grade 3 or higher cytopenias
were reported in 37% (100/269) of patients.
“These pivotal longer-term results from TRANSCEND NHL 001
continue to give us confidence in the clinical profile of liso-cel.
Importantly, these results were demonstrated in a study with more
than 250 patients in a broad population reflective of clinical
practice, including those with poor prognoses and a range of
histologies,” said Stanley Frankel, M.D., Senior Vice President,
Cellular Therapy Development for Bristol-Myers Squibb. “We look
forward to providing these data to support the regulatory approval
for this treatment option for these patients with large B-cell
lymphomas.”
Based on results from TRANSCEND NHL 001, Bristol-Myers Squibb
expects to complete the submission of a Biologics License
Application to the U.S. FDA by the end of the year.
Liso-cel is not approved for any use in any country.
About Diffuse Large B-cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL) is the most common and
aggressive NHL, accounting for three out of every five cases.
Approximately one-third of patients with DLBCL relapse after
receiving first-line treatment, and about 10% have refractory
disease. Historically, median life expectancy for patients who
relapse or are refractory to current standard of care treatments
following multiple lines of therapy is approximately six
months.
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.
About TRANSCEND NHL 001
TRANSCEND NHL 001 is an open-label, multicenter, pivotal phase 1
study to determine the safety, pharmacokinetics, and antitumor
activity of liso-cel in patients with relapsed/refractory B-cell
non-Hodgkin lymphoma, including diffuse large B-cell lymphoma,
high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma,
follicular lymphoma Grade 3B and mantle cell lymphoma. The primary
outcome measures were treatment-related adverse events,
dose-limiting toxicities and objective response rate. Secondary
outcome measures included complete response rate, duration of
response and progression-free survival.
About Lisocabtagene Maraleucel
(liso-cel)
Liso-cel is an investigational chimeric antigen receptor (CAR)
T-cell therapy designed to target CD19, which is a surface
glycoprotein expressed during normal B-cell development and
maintained following malignant transformation of B cells. Liso-cel
CAR T cells aim to target CD19 expressing cells through a CAR
construct that includes an anti-CD19 single-chain variable fragment
(scFv) targeting domain for antigen specificity, a transmembrane
domain, a 4-1BB costimulatory domain hypothesized to increase
T-cell proliferation and persistence, and a CD3-zeta T-cell
activation domain. The defined composition of CD4+ and CD8+ CAR T
cells in liso-cel may limit product variability; however, the
clinical significance of defined composition is unknown.
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.
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 liso-cel may not 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.
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