Heavily pre-treated patients with chronic
lymphocytic leukemia receiving liso-cel achieved durable complete
responses, including undetectable minimal residual disease
Preliminary data from the PILOT study showed
promising efficacy and safety as second-line therapy in patients
with aggressive relapsed or refractory large B-cell non-Hodgkin
lymphoma who were transplant ineligible
Separate analysis of patients treated in the
outpatient setting across three studies also presented
Bristol-Myers Squibb Company (NYSE: BMY) today
announced data from multiple studies evaluating lisocabtagene
maraleucel (liso-cel), an investigational CD19-directed CAR T-cell
therapy with a defined composition of purified CD8+ and CD4+ CAR T
cells, were presented during the 2019 ASH Annual Meeting in
Orlando, Fla. These studies included an evaluation of liso-cel in
patients with relapsed or refractory chronic lymphocytic leukemia
or small lymphocytic lymphoma (CLL/SLL) (TRANSCEND CLL 004); a
study in second-line patients with relapsed or refractory large
B-cell non-Hodgkin’s lymphoma (NHL) patients who were ineligible
for high-dose chemotherapy and hematopoietic stem cell transplant
(HSCT) (PILOT); and a separate analysis of patients with
relapsed/refractory large B-cell non-Hodgkin lymphoma who received
liso-cel in the outpatient setting across three studies.
“As we continue to evaluate liso-cel in important new disease
settings and areas of unmet medical need, we are encouraged to see
the early results from these studies,” said Stanley Frankel, M.D.,
Senior Vice President, Cellular Therapy Development for
Bristol-Myers Squibb. “The results in relapsed or refractory CLL
and SLL demonstrated a high rate of durable complete responses
achieved in heavily pre-treated patients, including patients who
have failed ibrutinib and venetoclax. We are encouraged by the
potential of liso-cel to treat second-line relapsed or refractory
large B-cell NHL patients who are not able to undergo a stem cell
transplant. Finally, the analysis evaluating liso-cel administered
in the outpatient setting demonstrates that not all patients
require hospitalization and that the safety and efficacy profile
across a variety of types of clinical sites is consistent.”
TRANSCEND CLL 004
In the phase 1/2 TRANSCEND CLL 004 study, at the data cutoff, 23
patients with CLL/SLL who had received at least three
(standard-risk disease) or two (high-risk disease) prior treatments
were evaluable for safety, with 22 patients evaluable for efficacy.
Patients had a median of 5 prior lines of therapy (range 2-11). All
patients (23/23) had received prior ibrutinib and most (21/23) were
refractory to or had relapsed on the BTK inhibitor. There were nine
patients (39%) that had failed both a BTK inhibitor (progressed on
treatment) and venetoclax (did not achieve a response after at
least 3 months). Most patients (83%) had high-risk features
including deletion 17p (35%, 8/23) and TP53 mutation (61%, 14/23).
Patients received liso-cel target doses of either 50 × 106 (n=9) or
100 × 106 (n=14) CAR+ T cells following lymphodepletion.
Treatment-emergent adverse events (TEAE) of any grade occurred
in 100% (23/23) of patients with 96% (22/23) of patients
experiencing a grade 3 or higher TEAE. The most common grade 3 or
higher TEAEs occurring in at least 25% of patients were anemia
(78%, 18/23), thrombocytopenia (70%, 16/23), neutropenia (56.5%,
13/23), leukopenia (43.5%, 10/23), febrile neutropenia (26%, 6/23),
lymphopenia (26%, 6/23) and cytokine release syndrome (9%,
2/23).
Seventy-four percent (17/23) of patients had cytokine release
syndrome (CRS) of any grade with 9% of patients (2/23) experiencing
grade 3 CRS. Thirty-nine percent (9/23) of patients had
neurological events (NE) of any grade, while 22% (5/23) of patients
had grade 3 or higher NE. Median time to onset of CRS was 4 days
(range 1-10 days) and of NE was 4 days (range 2-21). Incidence and
severity of CRS and NEs were similar for patients who failed a BTK
inhibitor and venetoclax. Seventy-four percent (17/23) of patients
received tocilizumab and/or corticosteroids. There were no grade 5
events.
At a median follow-up of 11 months, the overall response rate
(ORR) for patients receiving liso-cel was 81.5% (18/22, 95% CI:
59.7 – 94.8) with 45.5% (10/22) of patients achieving a complete
response (CR). In patients that had failed a BTK inhibitor and
venetoclax, the ORR was 89% (8/9, 95% CI: 51.8 – 99.7) with 67%
(6/9) achieving a CR. By day 30 following treatment, 68% (15/22) of
patients had achieved an early objective response with 10 of 12
responders at 6 months remaining progression-free after at least 9
months, and eight patients in response at 12 months or longer.
Among 20 patients evaluable for minimal residual disease (MRD), the
majority achieved undetectable MRD in the blood (75%) and bone
marrow (65%) by next-generation sequencing. All patients who
achieved undetectable MRD have maintained this status at last
follow-up.
PILOT
In the phase 2 PILOT study, patients had relapsed/refractory
large B-cell NHL, had received only 1 prior line of
immunochemotherapy and had been deemed ineligible for HSCT due to
patient factors including age, comorbidities or performance status.
Patients received liso-cel at a target dose of 100 × 106 CAR+ T
cells following lymphodepletion and could be treated in the
outpatient setting at the investigator’s discretion.
At the time of data cutoff, 19 patients had been leukapheresed,
with 13 patients receiving lymphodepletion followed by
liso-cel.
Of the 13 patients, eight (61.5%) had at least one grade 3 or
higher TEAE and these were primarily cytopenias. Four patients
(31%) had prolonged grade 3 or higher cytopenias at day 29. No
patients had grade 3 or higher CRS and no patients experienced NE
of any grade. Grade 1-2 CRS occurred in 3 (23%) patients. There
were no grade 5 TEAEs. Finally, of the 6 patients treated in the
outpatient setting, none were admitted to the hospital in the first
29 days following liso-cel infusion.
All 12 (100%) patients eligible for response evaluation achieved
a response with 6 (50%) patients achieving a CR. Seven of 12 (58%)
patients maintained response levels at 3 months following liso-cel
infusion.
Outpatient
Administration
A report of the safety and efficacy of liso-cel in patients with
relapsed/refractory large B-cell NHL treated in the outpatient
treatment setting was also presented. The analysis encompassed
three studies including OUTREACH (n=13), the only trial evaluating
CAR T-cell therapy in an outpatient setting at non-university
centers, including treatment sites not accredited by the Foundation
for the Accreditation of Cellular Therapy. The analysis also
included TRANSCEND NHL 001 (n=25) and PILOT (n=6).
Outpatient treatment required patient education regarding CAR
T-cell therapy, a caregiver and proximity to the treatment
location. Additionally, each site was required to have specific
readiness plans for patient care and monitoring for AEs, such as
CRS and NE, in the outpatient setting.
In the analysis, at data cutoff, 44 patients treated in the
outpatient setting from across the studies were evaluated and
received liso-cel on day 1. Seventeen (39%) patients had CRS of any
grade, while 13 (30%) patients had NE (n=13) of any grade. There
was 1 case of grade 3 or higher CRS and 2 cases of grade 3 or
higher NE and these were reversible. A total of 9 patients received
supportive tocilizumab and/or corticosteroids. Fifty-five percent
(24/44) of patients required hospitalization at some point and
these were all from TRANSCEND or OUTREACH. Of these patients, 9
(20%) were admitted on study day 4 or earlier. Two (5%) patients
required intensive care unit-level care lasting a median of 4 days.
No patients from PILOT were admitted to hospital in the first 29
days. Following treatment, the median time to hospitalization was 5
days (range 2-22) and the median length of stay was 6.5 days (range
1-23). TEAEs of any grade reported in at least 20% of patients
included fatigue, neutropenia, decreased appetite, CRS, anemia,
constipation, nausea, headache, cough, dizziness, hypotension,
thrombocytopenia, vomiting, back pain, diarrhea hypomagnesemia and
tremor.
Across the studies, the ORR was 80% (35/44) with 55% (24/44) of
patients achieving a complete response.
Liso-cel is not approved for any indication in any country.
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 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 achieve its primary study
endpoints or receive regulatory approval for the indications
described in this release in the currently anticipated timeline or
at all and, if approved, whether such product candidate for such
indications 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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