BMS compounds to be featured in more than 80 presentations
spanning 20 types of cancer, with focus on research of precision
therapies aimed at improving standards of care
First efficacy data for investigational anti-LAG-3 in
combination with Opdivo in anti-PD-1/PD-L1 relapsed or refractory
patients and for Opdivo in combination with epacadostat showcases
next wave of cancer research approaches
Opdivo plus Yervoy data to be featured in 18 presentations
across multiple tumor types, including advanced small cell lung
cancer, melanoma and colorectal cancer
Bristol-Myers Squibb Company (NYSE:BMY) today announced that
more than 80 presentations, including 16 oral presentations and
seven poster discussions, highlighting data from Company-sponsored
studies, collaborations and investigator-sponsored research
evaluating its oncology compounds across 20 types of cancer, will
be featured at the American Society of Clinical Oncology (ASCO)
Annual Meeting 2017 in Chicago from June 2-6. Results to be
presented represent the breadth of the Company’s Oncology research
portfolio, including monotherapy and combination studies of Opdivo
(nivolumab) and Yervoy (ipilimumab), as well as studies of
Empliciti (elotuzumab) and Sprycel (dasatinib). The Company will
also present updates from its robust investigational pipeline,
including proof-of-concept efficacy data for its anti-lymphocyte
activation gene-3 (LAG-3) monoclonal antibody in combination with
Opdivo and pharmacokinetic, pharmacodynamic and safety data on its
investigational glucocorticoid-induced tumor necrosis factor
receptor-related gene (GITR) agonist alone and for the first time,
in combination with Opdivo in advanced solid tumors.
Several presentations will report data from clinical
collaborations supportive of the Company’s efforts to advance
understanding of the potential role for Opdivo in combination with
novel mechanisms of action for several tumor types, including the
first presentation of data evaluating the safety and efficacy of
Opdivo in combination with epacadostat, Incyte’s selective IDO1
enzyme inhibitor. Presentations featuring translational medicine
research underscore Bristol-Myers Squibb’s scientific leadership in
driving understanding of how a patient’s tumor biology can
potentially guide treatment decisions.
Data from research on the Company’s medicines to be presented
during the meeting include:
Gastrointestinal
Malignancies
- Combination of nivolumab +
ipilimumab in the treatment of patients with deficient DNA mismatch
repair/high microsatellite instability metastatic colorectal
cancer: CheckMate 142 studyAuthor: Thierry AndreAbstract
#3531Poster Session: Gastrointestinal (Colorectal) CancerSaturday,
June 3, 8:00–11:30 AM, Hall A
- Concordance of DNA mismatch repair
deficient/microsatellite instability assessment by local and
central testing in patients with metastatic CRC receiving nivolumab
in CheckMate 142Author: Scott KopetzAbstract #3548Poster
Session: Gastrointestinal (Colorectal) CancerSaturday, June 3,
8:00–11:30 AM, Hall A
- Nivolumab in sorafenib-naive and
-experienced patients with advanced hepatocellular carcinoma: The
CheckMate 040 studyAuthor: Todd S. CrocenziAbstract #4013Poster
Discussion Session: Gastrointestinal (Noncolorectal)
CancerSaturday, June 3, 8:00–11:30 AM, Hall ADiscussed at the
Poster Discussion Session on Saturday, June 3, 2017, 4:45–6:00 PM,
Hall D2
- CheckMate 577: A randomized,
double-blind, phase 3 study of adjuvant nivolumab or placebo in
patients with resected esophageal or gastroesophageal junction
cancerAuthor: Ronan Joseph KellyAbstract #TPS4131Poster
Session: Gastrointestinal (Noncolorectal) CancerSaturday, June 3,
8:00–11:30 AM, Hall A
- CheckMate 649: A randomized,
multicenter, open-label, phase 3 study of nivolumab + ipilimumab or
nivo + chemotherapy vs CTX alone in patients with previously
untreated advanced gastric or gastroesophageal junction
cancerAuthor: Markus H. MoehlerAbstract #TPS4132Poster Session:
Gastrointestinal (Noncolorectal) CancerSaturday, June 3, 8:00–11:30
AM, Hall A
- Nivolumab ± ipilimumab in patients
with advanced/metastatic chemotherapy-refractory gastric,
esophageal or gastroesophageal junction cancer: CheckMate 032
studyAuthor: Yelena Yuriy JanjigianAbstract #4014Oral Abstract
Session: Gastrointestinal (Noncolorectal) CancerSunday, June 4,
9:24–9:36 AM, Hall D2
Genitourinary Cancer
- Health-related quality of life as a
marker of treatment benefit with nivolumab in platinum-refractory
patients with metastatic or unresectable urothelial carcinoma from
CheckMate 275Author: Andrea NecchiAbstract #4526Poster Session:
Genitourinary (Nonprostate) CancerSunday, June 4, 8:00–11:30 AM,
Hall A
Glioblastoma
- Histopathologic review of suspected
disease progression in patients with recurrent glioblastoma
receiving nivolumab ± ipilimumab: CheckMate 143Author: Solmaz
SahebjamAbstract #2001Oral Abstract Session: Central Nervous System
TumorsSunday, June 4, 8:12–8:24 AM, S100a
- Overall survival by line of therapy
in Medicare-enrolled glioblastoma multiforme patientsAuthor:
Abdalla AlyAbstract #2039Poster Session: Central Nervous System
TumorsMonday, June 5, 1:15–4:45 PM, Hall A
Gynecologic Cancers
- An open-label, multicohort, phase
1/2 study of nivolumab in patients with virus-associated tumors
(CheckMate 358): Efficacy and safety in recurrent or metastatic
cervical, vaginal and vulvar cancersAuthor: Antoine
HollebecqueAbstract #5504Oral Abstract Session: Gynecologic
CancerFriday, June 2, 4:12–4:24 PM, S406
Head and Neck Cancer
- Nivolumab vs investigator’s choice
for platinum-refractory recurrent or metastatic squamous cell
carcinoma of the head and neck (Checkmate 141): Outcomes in
first-line R/M patients and updated safety and efficacyAuthor:
Maura L. GillisonAbstract #6019Poster Discussion Session: Head and
Neck CancerMonday, June 5, 1:15–4:45 PM, Hall ADiscussed at the
Poster Discussion Session on Monday, June 5, 2017, 4:45–6:00 PM,
S406
- Nivolumab vs investigator’s choice
in patients with recurrent or metastatic squamous cell carcinoma of
the head and neck: Efficacy and safety in CheckMate 141 by prior
cetuximab useAuthor: Robert L. FerrisAbstract #6020Poster
Discussion Session: Head and Neck CancerMonday, June 5, 1:15–4:45
PM, Hall ADiscussed at the Poster Discussion Session on Monday,
June 5, 2017, 4:45–6:00 PM, S406
- An open-label, multicohort, phase
1/2 study to evaluate nivolumab in patients with virus-associated
tumors (CheckMate 358): Efficacy and safety in recurrent or
metastatic nasopharyngeal carcinomaAuthor: Jean-Pierre
DelordAbstract #6025Poster Session: Head and Neck CancerMonday,
June 5, 1:15–4:45 PM, Hall A
- Characterization of potential
predictive biomarkers of response to nivolumab in CheckMate 141 in
patients with squamous cell carcinoma of the head and
neckAuthor: Fernando Concha-BenaventeAbstract #6050Poster
Session: Head and Neck CancerMonday, June 5, 1:15–4:45 PM, Hall
A
Hematologic Malignancies
- Phase 2 trial of dasatinib in
pediatric patients with chronic myeloid leukemia in chronic
phaseAuthor: Lia GoreAbstract #10511Oral Abstract Session:
Pediatric Oncology IIMonday, June 5, 8:24–8:36 AM, S504
- Impact of dose reductions on 5-year
efficacy in newly diagnosed patients with chronic myeloid leukemia
in chronic phase from DASISIONAuthor: Jorge E. CortesAbstract
#7051Poster Session: Hematologic Malignancies—Leukemia,
Myelodysplastic Syndromes, and AllotransplantMonday, June 5,
8:00–11:30 AM, Hall A
- Phase 3 ELOQUENT-2 study: Extended
four-year follow-up of elotuzumab plus lenalidomide/dexamethasone
vs Ld in relapsed/refractory multiple myelomaAuthor: Sagar
LonialAbstract #8028Poster Session: Hematologic Malignancies—Plasma
Cell DyscrasiaMonday, June 5, 8:00–11:30 AM, Hall A
- Nivolumab in combination with
daratumumab, with or without pomalidomide and dexamethasone, for
relapsed/refractory multiple myeloma: 2 cohorts of the phase 1
CheckMate 039 safety studyAuthor: Alexander M. LesokhinAbstract
#TPS3102Poster Session: Developmental
Therapeutics—ImmunotherapyMonday, June 5, 8:00–11:30 AM, Hall
A
- CheckMate 436: A phase 1/2 study to
evaluate safety and efficacy of nivolumab plus brentuximab vedotin
in patients with CD30-expressing relapsed/refractory non-Hodgkin
lymphomasAuthor: Paul M. BarrAbstract #TPS7577Poster Session:
Hematologic Malignancies—Lymphoma and Chronic Lymphocytic
LeukemiaMonday, June 5, 8:00–11:30 AM, Hall A
- CheckMate 602: An open-label,
randomized, phase 3 trial of combinations of nivolumab, elotuzumab,
pomalidomide and dexamethasone in relapsed/refractory multiple
myelomaAuthor: Sagar LonialAbstract #TPS8052Poster Session:
Hematologic Malignancies—Plasma Cell DyscrasiaMonday, June 5,
8:00–11:30 AM, Hall A
Melanoma
- Overall survival analysis from an
expanded access program of nivolumab in combination with ipilimumab
in patients with advanced melanoma (CheckMate 218)Author: David
HoggAbstract #9522Poster Session: Melanoma/Skin CancersSaturday,
June 3, 1:15–4:45 PM, Hall A
- Association of distinct baseline
tissue biomarkers with response to nivolumab and ipilimumab in
melanoma: CheckMate 064Author: Scott RodigAbstract #9515Poster
Discussion Session: Melanoma/Skin CancersSaturday, June 3,
1:15–4:45 PM, Hall ADiscussed at the Poster Discussion Session on
Saturday, June 3, 2017, 4:45–6:00 PM, E354b
- Management of gastrointestinal
toxicity associated with nivolumab plus ipilimumab (IPI) or IPI
alone in phase 2 and 3 trials in advanced melanomaAuthor:
Jeffrey S. WeberAbstract #9523Poster Session: Melanoma/Skin
CancersSaturday, June 3, 1:15–4:45 PM, Hall A
- Efficacy and safety of nivolumab in
patients with advanced melanoma and poor prognostic factors who
progressed on or after ipilimumab: Results from a phase 2 study
(CheckMate 172)Author: Dirk SchadendorfAbstract #9524Poster
Session: Melanoma/Skin CancersSaturday, June 3, 1:15–4:45 PM, Hall
A
- Efficacy and safety of nivolumab
plus ipilimumab in patients with melanoma metastatic to the brain:
Results of the phase 2 study CheckMate 204Author: Hussein
Abdul-Hassan TawbiAbstract #9507Oral Abstract Session:
Melanoma/Skin CancersSunday, June 4, 10:12–10:24 AM, Arie Crown
Theater
Thoracic Malignancies
- Nivolumab plus ipilimumab as
first-line treatment for advanced NSCLC: 2-year OS and long-term
outcomes from CheckMate 012Author: Jonathan Wade
GoldmanAbstract #9093Poster Session: Lung Cancer—Non-Small Cell
MetastaticSaturday, June 3, 8:00–11:30 AM, Hall A
- Checkmate 816: A phase 3,
randomized, open-label trial of nivolumab plus ipilimumab vs
platinum-doublet chemotherapy as neoadjuvant treatment for
early-stage NSCLCAuthor: Patrick M. FordeAbstract
#TPS8577Poster Session: Lung Cancer—Non-Small Cell
Local-Regional/Small Cell/Other Thoracic CancersSaturday, June 3,
8:00–11:30 AM, Hall A
- Checkmate 743: A phase 3,
randomized, open-label trial of nivolumab plus ipilimumab vs
pemetrexed plus cisplatin or carboplatin as first-line therapy in
unresectable pleural mesotheliomaAuthor: Gerard ZalcmanAbstract
#TPS8581Poster Session: Lung Cancer—Non-Small Cell
Local-Regional/Small Cell/Other Thoracic CancersSaturday, June 3,
8:00–11:30 AM, Hall A
- Nivolumab ± ipilimumab in advanced
small cell lung cancer: first report of a randomized expansion
cohort from CheckMate 032Author: Matthew David HellmannAbstract
#8503Oral Abstract Session: Lung Cancer—Non-Small Cell
Local-Regional/Small Cell/Other Thoracic CancersMonday, June 5,
9:00–9:12 AM, Hall B1
Pipeline
- FRACTION (Fast Real-time Assessment
of Combination Therapies in Immuno-ONcology)-gastric cancer (GC): A
randomized, open-label, adaptive phase 2 study of nivolumab in
combination with other immuno-oncology agents in patients with
advanced GCAuthor: Praveen AanurAbstract #TPS4137Poster
Session: Gastrointestinal (Noncolorectal) CancerSaturday, June 3,
8:00–11:30 AM, Hall A
- Initial efficacy of anti-lymphocyte
activation gene-3 (anti–LAG-3; BMS-986016) in combination with
nivolumab in patients with melanoma previously treated with
anti–PD-1/PD-L1 therapyAuthor: Paolo Antonio AsciertoAbstract
#9520Poster Discussion Session: Melanoma/Skin CancersSaturday, June
3, 1:15–4:45 PM, Hall ADiscussed at the Poster Discussion Session
on Saturday, June 3, 2017, 4:45–6:00 PM, E354b
- Preliminary results of a phase 1/2a
study of BMS-986156 (glucocorticoid-induced tumor necrosis factor
receptor–related gene [GITR] agonist), alone and in combination
with nivolumab in patients with advanced solid tumorsAuthor:
Lillian L. SiuAbstract #104Clinical Science Symposium: "Check" This
Out: The Step Beyond PD-1 BlockadeSunday, June 4, 10:12–10:24 AM,
Hall D1
Clinical Collaborations
- Nivolumab + nab-paclitaxel +
carboplatin in patients with non-small cell lung cancer: Interim
results from a multicenter phase 1 studyAuthor: David Michael
WaterhouseAbstract #9095Poster Session: Lung Cancer—Non-Small Cell
MetastaticSaturday, June 3, 8:00–11:30 AM, Hall A
-
Ceritinib plus nivolumab in patients with
anaplastic lymphoma kinase positive (ALK+) advanced non-small cell
lung cancer Author: Enriqueta FelipAbstract #2502Oral Abstract
Session: Developmental Therapeutics—Clinical Pharmacology and
Experimental TherapeuticsSaturday, June 3, 1:39–1:51 PM,
E450ab
- Effect of a novel IL-2 cytokine
immune agonist (NKTR-214) on proliferating CD8+T cells and PD-1
expression on immune cells in the tumor microenvironment in
patients with prior checkpoint therapyAuthor: Chantale
BernatchezAbstract #2545Poster Session: Developmental
Therapeutics—Clinical Pharmacology and Experimental
TherapeuticsMonday, June 5, 8:00–11:30 AM, Hall A
- A phase I study
of enadenotucirev (EnAd), an oncolytic Ad11/Ad3 chimeric group
B adenovirus, in combination with nivolumab in tumors of epithelial
originAuthor: Wael A. HarbAbstract #TPS3115Poster Session:
Developmental Therapeutics—ImmunotherapyMonday, June 5, 8:00–11:30
AM, Hall A
- Epacadostat plus nivolumab
in patients with advanced solid tumors: Preliminary phase 1/2
results of ECHO-204Author: Raymond P. PerezAbstract #3003Oral
Abstract Session: Developmental Therapeutics—ImmunotherapyMonday,
June 5, 2:15–2:27 PM, Hall D1
- Clinical results with combination of
anti-CD27 agonist antibody, varlilumab, with anti-PD1 antibody
nivolumab in advanced cancer patientsAuthor: Rachel E.
SanbornAbstract #3007Oral Abstract Session: Developmental
Therapeutics—ImmunotherapyMonday, June 5, 3:27–3:39 PM, Hall
D1
International Immuno-Oncology Network
(II-ON)
- Function and expression of
checkpoint inhibitors and immune agonists on immune cells in
monoclonal gammopathy of undetermined significance,
smoldering multiple myeloma and MM and tumor-specific T
lymphocytesAuthor: Jooeun BaeAbstract #11577Poster
Session: Tumor BiologySaturday, June 3, 1:15–4:45 PM, Hall A
- Loss-of-function of PBRM1 to predict
response to anti-PD-1/PD-L1 therapy in metastatic renal cell
carcinomaAuthor: Diana MiaoAbstract #3016Poster Session:
Developmental Therapeutics—ImmunotherapyMonday, June 5, 8:00–11:30
AM, Hall ADiscussed at the Poster Discussion Session on Monday,
June 5, 2017, 4:45–6:00 PM, Hall D1
- Metabolomic correlates of
response in nivolumab-treated renal cell carcinoma and melanoma
patientsAuthor: Marios GiannakisAbstract #3036Poster Session:
Developmental Therapeutics—ImmunotherapyMonday, June 5, 8:00–11:30
AM, Hall A
Bristol-Myers Squibb &
Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, patients are at the center of
everything we do. Our vision for the future of cancer care is
focused on researching and developing transformational
Immuno-Oncology (I-O) medicines for hard-to-treat cancers that
could potentially improve outcomes for these patients.
We are leading the scientific understanding of I-O through our
extensive portfolio of investigational compounds and approved
agents. Our differentiated clinical development program is studying
broad patient populations across more than 35 types of cancers with
14 clinical-stage molecules designed to target different immune
system pathways. Our deep expertise and innovative clinical trial
designs position us to advance I-O/I-O, I-O/chemotherapy,
I-O/targeted therapies and I-O/radiation therapies across multiple
tumors and potentially deliver the next wave of therapies with a
sense of urgency. We also continue to pioneer research that will
help facilitate a deeper understanding of the role of immune
biomarkers and how patients’ individual tumor biology can be used
as a guide for treatment decisions throughout their journey.
We understand making the promise of I-O a reality for the many
patients who may benefit from these therapies requires not only
innovation on our part but also close collaboration with leading
experts in the field. Our partnerships with academia, government,
advocacy and biotech companies support our collective goal of
providing new treatment options to advance the standards of
clinical practice.
About the International Immuno-Oncology
Network (II-ON)
The II-ON, formed in 2012, is a global peer-to-peer
collaboration between Bristol-Myers Squibb and academia advancing
the science of Immuno-Oncology (I-O) through a series of
preclinical, translational and biology-focused research objectives.
The research in the collaboration is focused on three fundamental
scientific pillars: understanding the mechanisms of resistance to
immunotherapy; identifying patient populations likely to benefit
from immunotherapy; and exploring novel combination therapies that
may enhance anti-tumor response through complementary mechanisms of
action. The II-ON facilitates the translation of scientific
research findings into drug discovery and development, with the
goal of introducing new treatment options into clinical
practice.
In addition to Bristol-Myers Squibb, the II-ON currently
comprises 15 leading cancer research institutions, including:
Clinica Universidad Navarra, Columbia University Medical Center,
Dana-Farber Cancer Institute, The Earle A. Chiles Research
Institute (Providence Health & Services), Institut Gustave
Roussy, Istituto Nazionale per lo Studio e la Cura dei
Tumori “Fondazione G. Pascale”, Bloomberg-Kimmel Institute for
Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center,
Memorial Sloan Kettering Cancer Center, National Cancer Center
Japan, The Netherlands Cancer Institute, Peter MacCallum
Cancer Centre, The Royal Marsden NHS Foundation
Trust and The Institute of Cancer Research, University
College London, The University of Chicago and West German
Cancer Center/University Hospital Essen.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint
inhibitor that is designed to uniquely harness the body’s own
immune system to help restore anti-tumor immune response. By
harnessing the body’s own immune system to fight cancer, Opdivo has
become an important treatment option across multiple cancers.
Opdivo’s leading global development program is based on
Bristol-Myers Squibb’s scientific expertise in the field of
Immuno-Oncology and includes a broad range of clinical trials
across all phases, including Phase 3, in a variety of tumor types.
To date, the Opdivo clinical development program has enrolled more
than 25,000 patients. The Opdivo trials have contributed to gaining
a deeper understanding of the potential role of biomarkers in
patient care, particularly regarding how patients may benefit from
Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint
inhibitor to receive regulatory approval anywhere in the world.
Opdivo is currently approved in more than 60 countries, including
the United States, the European Union and Japan. In October 2015,
the company’s Opdivo and Yervoy combination regimen was the first
Immuno-Oncology combination to receive regulatory approval for the
treatment of metastatic melanoma and is currently approved in more
than 50 countries, including the United States and the European
Union.
U.S. FDA-APPROVED INDICATIONS FOR
OPDIVO®
OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 mutation-positive unresectable
or metastatic melanoma. This indication is approved under
accelerated approval based on progression-free survival. Continued
approval for this indication may be contingent upon verification
and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 wild-type unresectable or
metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab),
is indicated for the treatment of patients with unresectable or
metastatic melanoma. This indication is approved under accelerated
approval based on progression-free survival. Continued approval for
this indication may be contingent upon verification and description
of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with metastatic non-small cell lung cancer (NSCLC) with progression
on or after platinum-based chemotherapy. Patients with EGFR or ALK
genomic tumor aberrations should have disease progression on
FDA-approved therapy for these aberrations prior to receiving
OPDIVO.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with advanced renal cell carcinoma (RCC) who have received prior
anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with classical Hodgkin lymphoma (cHL) that has relapsed or
progressed after autologous hematopoietic stem cell transplantation
(HSCT) and post-transplantation brentuximab vedotin. This
indication is approved under accelerated approval based on overall
response rate. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in
confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with recurrent or metastatic squamous cell carcinoma of the head
and neck (SCCHN) with disease progression on or after
platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with locally advanced or metastatic urothelial carcinoma who have
disease progression during or following platinum-containing
chemotherapy or have disease progression within 12 months of
neoadjuvant or adjuvant treatment with platinum-containing
chemotherapy. This indication is approved under accelerated
approval based on tumor response rate and duration of response.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory
trials.
IMPORTANT SAFETY
INFORMATION
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS
YERVOY can result in severe and fatal immune-mediated adverse
reactions. These immune-mediated reactions may involve any organ
system; however, the most common severe immune-mediated adverse
reactions are enterocolitis, hepatitis, dermatitis (including toxic
epidermal necrolysis), neuropathy, and endocrinopathy. The majority
of these immune-mediated reactions initially manifested during
treatment; however, a minority occurred weeks to months after
discontinuation of YERVOY.
Assess patients for signs and symptoms of enterocolitis,
dermatitis, neuropathy, and endocrinopathy and evaluate clinical
chemistries including liver function tests (LFTs),
adrenocorticotropic hormone (ACTH) level, and thyroid function
tests at baseline and before each dose.
Permanently discontinue YERVOY and initiate systemic
high-dose corticosteroid therapy for severe immune-mediated
reactions.
Immune-Mediated Pneumonitis
OPDIVO can cause immune-mediated pneumonitis. Fatal cases have
been reported. Monitor patients for signs with radiographic imaging
and for symptoms of pneumonitis. Administer corticosteroids for
Grade 2 or more severe pneumonitis. Permanently discontinue for
Grade 3 or 4 and withhold until resolution for Grade 2. In patients
receiving OPDIVO monotherapy, fatal cases of immune-mediated
pneumonitis have occurred. Immune-mediated pneumonitis occurred in
3.1% (61/1994) of patients. In patients receiving OPDIVO with
YERVOY, immune-mediated pneumonitis occurred in 6% (25/407) of
patients.
In Checkmate 205 and 039, pneumonitis, including interstitial
lung disease, occurred in 4.9% (13/263) of patients receiving
OPDIVO. Immune-mediated pneumonitis occurred in 3.4% (9/263) of
patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=8).
Immune-Mediated Colitis
OPDIVO can cause immune-mediated colitis. Monitor patients for
signs and symptoms of colitis. Administer corticosteroids for Grade
2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO
monotherapy for Grade 2 or 3 and permanently discontinue for Grade
4 or recurrent colitis upon re-initiation of OPDIVO. When
administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2
and permanently discontinue for Grade 3 or 4 or recurrent colitis.
In patients receiving OPDIVO monotherapy, immune-mediated colitis
occurred in 2.9% (58/1994) of patients. In patients receiving
OPDIVO with YERVOY, immune-mediated colitis occurred in 26%
(107/407) of patients including three fatal cases.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe,
life-threatening, or fatal (diarrhea of ≥7 stools above baseline,
fever, ileus, peritoneal signs; Grade 3-5) immune-mediated
enterocolitis occurred in 34 (7%) patients. Across all
YERVOY-treated patients in that study (n=511), 5 (1%) developed
intestinal perforation, 4 (0.8%) died as a result of complications,
and 26 (5%) were hospitalized for severe enterocolitis.
Immune-Mediated Hepatitis
OPDIVO can cause immune-mediated hepatitis. Monitor patients for
abnormal liver tests prior to and periodically during treatment.
Administer corticosteroids for Grade 2 or greater transaminase
elevations. Withhold for Grade 2 and permanently discontinue for
Grade 3 or 4 immune-mediated hepatitis. In patients receiving
OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8%
(35/1994) of patients. In patients receiving OPDIVO with YERVOY,
immune-mediated hepatitis occurred in 13% (51/407) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe,
life-threatening, or fatal hepatotoxicity (AST or ALT elevations
>5x the ULN or total bilirubin elevations >3x the ULN; Grade
3-5) occurred in 8 (2%) patients, with fatal hepatic failure in
0.2% and hospitalization in 0.4%.
Immune-Mediated Neuropathies
In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal
Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral
motor neuropathy were reported.
Immune-Mediated Endocrinopathies
OPDIVO can cause immune-mediated hypophysitis, immune-mediated
adrenal insufficiency, autoimmune thyroid disorders, and Type 1
diabetes mellitus. Monitor patients for signs and symptoms of
hypophysitis, signs and symptoms of adrenal insufficiency, thyroid
function prior to and periodically during treatment, and
hyperglycemia. Administer hormone replacement as clinically
indicated and corticosteroids for Grade 2 or greater hypophysitis.
Withhold for Grade 2 or 3 and permanently discontinue for Grade 4
hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal
insufficiency. Withhold for Grade 2 and permanently discontinue for
Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement
therapy for hypothyroidism. Initiate medical management for control
of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently
discontinue for Grade 4 hyperglycemia.
In patients receiving OPDIVO monotherapy, hypophysitis occurred
in 0.6% (12/1994) of patients. In patients receiving OPDIVO with
YERVOY, hypophysitis occurred in 9% (36/407) of patients. In
patients receiving OPDIVO monotherapy, adrenal insufficiency
occurred in 1% (20/1994) of patients. In patients receiving OPDIVO
with YERVOY, adrenal insufficiency occurred in 5% (21/407) of
patients. In patients receiving OPDIVO monotherapy, hypothyroidism
or thyroiditis resulting in hypothyroidism occurred in 9%
(171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994)
of patients receiving OPDIVO monotherapy. In patients receiving
OPDIVO with YERVOY, hypothyroidism or thyroiditis resulting in
hypothyroidism occurred in 22% (89/407) of patients.
Hyperthyroidism occurred in 8% (34/407) of patients receiving
OPDIVO with YERVOY. In patients receiving OPDIVO monotherapy,
diabetes occurred in 0.9% (17/1994) of patients. In patients
receiving OPDIVO with YERVOY, diabetes occurred in 1.5% (6/407) of
patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe to
life-threatening immune-mediated endocrinopathies (requiring
hospitalization, urgent medical intervention, or interfering with
activities of daily living; Grade 3-4) occurred in 9 (1.8%)
patients. All 9 patients had hypopituitarism, and some had
additional concomitant endocrinopathies such as adrenal
insufficiency, hypogonadism, and hypothyroidism. 6 of the 9
patients were hospitalized for severe endocrinopathies.
Immune-Mediated Nephritis and Renal Dysfunction
OPDIVO can cause immune-mediated nephritis. Monitor patients for
elevated serum creatinine prior to and periodically during
treatment. Administer corticosteroids for Grades 2-4 increased
serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently
discontinue for Grade 4 increased serum creatinine. In patients
receiving OPDIVO monotherapy, immune-mediated nephritis and renal
dysfunction occurred in 1.2% (23/1994) of patients. In patients
receiving OPDIVO with YERVOY, immune-mediated nephritis and renal
dysfunction occurred in 2.2% (9/407) of patients.
Immune-Mediated Skin Adverse Reactions and Dermatitis
OPDIVO can cause immune-mediated rash, including Stevens-Johnson
syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases
with fatal outcome. Administer corticosteroids for Grade 3 or 4
rash. Withhold for Grade 3 and permanently discontinue for Grade 4
rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and
refer the patient for specialized care for assessment and
treatment; if confirmed, permanently discontinue. In patients
receiving OPDIVO monotherapy, immune-mediated rash occurred in 9%
(171/1994) of patients. In patients receiving OPDIVO with YERVOY,
immune-mediated rash occurred in 22.6% (92/407) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe,
life-threatening, or fatal immune-mediated dermatitis (eg,
Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash
complicated by full thickness dermal ulceration, or necrotic,
bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13
(2.5%) patients. 1 (0.2%) patient died as a result of toxic
epidermal necrolysis. 1 additional patient required hospitalization
for severe dermatitis.
Immune-Mediated Encephalitis
OPDIVO can cause immune-mediated encephalitis. Evaluation of
patients with neurologic symptoms may include, but not be limited
to, consultation with a neurologist, brain MRI, and lumbar
puncture. Withhold OPDIVO in patients with new-onset moderate to
severe neurologic signs or symptoms and evaluate to rule out other
causes. If other etiologies are ruled out, administer
corticosteroids and permanently discontinue OPDIVO for
immune-mediated encephalitis. In patients receiving OPDIVO
monotherapy, encephalitis occurred in 0.2% (3/1994) of patients.
Fatal limbic encephalitis occurred in one patient after 7.2 months
of exposure despite discontinuation of OPDIVO and administration of
corticosteroids. Encephalitis occurred in one patient receiving
OPDIVO with YERVOY (0.2%) after 1.7 months of exposure.
Other Immune-Mediated Adverse Reactions
Based on the severity of adverse reaction, permanently
discontinue or withhold treatment, administer high-dose
corticosteroids, and, if appropriate, initiate hormone-replacement
therapy. Across clinical trials of OPDIVO the following clinically
significant immune-mediated adverse reactions occurred in <1.0%
of patients receiving OPDIVO: uveitis, iritis, pancreatitis, facial
and abducens nerve paresis, demyelination, polymyalgia rheumatica,
autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism,
systemic inflammatory response syndrome, gastritis, duodenitis,
sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi
lymphadenitis), myositis, myocarditis, rhabdomyolysis, motor
dysfunction, vasculitis, and myasthenic syndrome.
Infusion Reactions
OPDIVO can cause severe infusion reactions, which have been
reported in <1.0% of patients in clinical trials. Discontinue
OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt
or slow the rate of infusion in patients with Grade 1 or 2. In
patients receiving OPDIVO monotherapy, infusion-related reactions
occurred in 6.4% (127/1994) of patients. In patients receiving
OPDIVO with YERVOY, infusion-related reactions occurred in 2.5%
(10/407) of patients.
Complications of Allogeneic HSCT after OPDIVO
Complications, including fatal events, occurred in patients who
received allogeneic HSCT after OPDIVO. Outcomes were evaluated in
17 patients from Checkmate 205 and 039, who underwent allogeneic
HSCT after discontinuing OPDIVO (15 with reduced-intensity
conditioning, 2 with myeloablative conditioning). Thirty-five
percent (6/17) of patients died from complications of allogeneic
HSCT after OPDIVO. Five deaths occurred in the setting of severe or
refractory GVHD. Grade 3 or higher acute GVHD was reported in 29%
(5/17) of patients. Hyperacute GVHD was reported in 20% (n=2) of
patients. A steroid-requiring febrile syndrome, without an
identified infectious cause, was reported in 35% (n=6) of patients.
Two cases of encephalitis were reported: Grade 3 (n=1) lymphocytic
encephalitis without an identified infectious cause, and Grade 3
(n=1) suspected viral encephalitis. Hepatic veno-occlusive disease
(VOD) occurred in one patient, who received reduced-intensity
conditioned allogeneic HSCT and died of GVHD and multi-organ
failure. Other cases of hepatic VOD after reduced-intensity
conditioned allogeneic HSCT have also been reported in patients
with lymphoma who received a PD-1 receptor blocking antibody before
transplantation. Cases of fatal hyperacute GVHD have also been
reported. These complications may occur despite intervening therapy
between PD-1 blockade and allogeneic HSCT.
Follow patients closely for early evidence of transplant-related
complications such as hyperacute GVHD, severe (Grade 3 to 4) acute
GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other
immune-mediated adverse reactions, and intervene promptly.
Embryo-Fetal Toxicity
Based on their mechanisms of action, OPDIVO and YERVOY can cause
fetal harm when administered to a pregnant woman. Advise pregnant
women of the potential risk to a fetus. Advise females of
reproductive potential to use effective contraception during
treatment with an OPDIVO- or YERVOY- containing regimen and for at
least 5 months after the last dose of OPDIVO.
Lactation
It is not known whether OPDIVO or YERVOY is present in human
milk. Because many drugs, including antibodies, are excreted in
human milk and because of the potential for serious adverse
reactions in nursing infants from an OPDIVO-containing regimen,
advise women to discontinue breastfeeding during treatment. Advise
women to discontinue nursing during treatment with YERVOY and for 3
months following the final dose.
Serious Adverse Reactions
In Checkmate 037, serious adverse reactions occurred in 41% of
patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions
occurred in 42% of patients receiving OPDIVO. The most frequent
Grade 3 and 4 adverse drug reactions reported in 2% to <5% of
patients receiving OPDIVO were abdominal pain, hyponatremia,
increased aspartate aminotransferase, and increased lipase. In
Checkmate 066, serious adverse reactions occurred in 36% of
patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions
occurred in 41% of patients receiving OPDIVO. The most frequent
Grade 3 and 4 adverse reactions reported in ≥2% of patients
receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and
diarrhea (3.4%). In Checkmate 067, serious adverse reactions (73%
and 37%), adverse reactions leading to permanent discontinuation
(43% and 14%) or to dosing delays (55% and 28%), and Grade 3 or 4
adverse reactions (72% and 44%) all occurred more frequently in the
OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313).
The most frequent (≥10%) serious adverse reactions in the OPDIVO
plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea
(13% and 2.6%), colitis (10% and 1.6%), and pyrexia (10% and 0.6%).
In Checkmate 017 and 057, serious adverse reactions occurred in 46%
of patients receiving OPDIVO (n=418). The most frequent serious
adverse reactions reported in at least 2% of patients receiving
OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia,
pleural effusion, pneumonitis, and respiratory failure. In
Checkmate 025, serious adverse reactions occurred in 47% of
patients receiving OPDIVO (n=406). The most frequent serious
adverse reactions reported in ≥2% of patients were acute kidney
injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia.
In Checkmate 205 and 039, among all patients (safety population
[n=263]), adverse reactions leading to discontinuation (4.2%) or to
dosing delays (23%) occurred. The most frequent serious adverse
reactions reported in ≥1% of patients were infusion-related
reaction, pneumonia, pleural effusion, pyrexia, rash and
pneumonitis. Ten patients died from causes other than disease
progression, including 6 who died from complications of allogeneic
HSCT. Serious adverse reactions occurred in 21% of patients in the
safety population (n=263) and 27% of patients in the subset of
patients evaluated for efficacy (efficacy population [n=95]). In
Checkmate 141, serious adverse reactions occurred in 49% of
patients receiving OPDIVO. The most frequent serious adverse
reactions reported in at least 2% of patients receiving OPDIVO were
pneumonia, dyspnea, respiratory failure, respiratory tract
infections, and sepsis. In Checkmate 275, serious adverse reactions
occurred in 54% of patients receiving OPDIVO (n=270). The most
frequent serious adverse reactions reported in at least 2% of
patients receiving OPDIVO were urinary tract infection, sepsis,
diarrhea, small intestine obstruction, and general physical health
deterioration.
Common Adverse Reactions
In Checkmate 037, the most common adverse reaction (≥20%)
reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the
most common adverse reactions (≥20%) reported with OPDIVO (n=206)
vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal
pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In
Checkmate 067, the most common (≥20%) adverse reactions in the
OPDIVO plus YERVOY arm (n=313) were fatigue (59%), rash (53%),
diarrhea (52%), nausea (40%), pyrexia (37%), vomiting (28%), and
dyspnea (20%). The most common (≥20%) adverse reactions in the
OPDIVO (n=313) arm were fatigue (53%), rash (40%), diarrhea (31%),
and nausea (28%). In Checkmate 017 and 057, the most common adverse
reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue,
musculoskeletal pain, cough, dyspnea, and decreased appetite. In
Checkmate 025, the most common adverse reactions (≥20%) reported in
patients receiving OPDIVO (n=406) vs everolimus (n=397) were
asthenic conditions (56% vs 57%), cough (34% vs 38%), nausea (28%
vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs
32%), constipation (23% vs 18%), decreased appetite (23% vs 30%),
back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate
205 and 039, among all patients (safety population [n=263]) and the
subset of patients in the efficacy population (n=95), respectively,
the most common adverse reactions (≥20%) were fatigue (32% and
43%), upper respiratory tract infection (28% and 48%), pyrexia (24%
and 35%), diarrhea (23% and 30%), and cough (22% and 35%). In the
subset of patients in the efficacy population (n=95), the most
common adverse reactions also included rash (31%), musculoskeletal
pain (27%), pruritus (25%), nausea (23%), arthralgia (21%), and
peripheral neuropathy (21%). In Checkmate 141, the most common
adverse reactions (≥10%) in patients receiving OPDIVO were cough
and dyspnea at a higher incidence than investigator’s choice. In
Checkmate 275, the most common adverse reactions (≥ 20%) reported
in patients receiving OPDIVO (n=270) were fatigue (46%),
musculoskeletal pain (30%), nausea (22%), and decreased appetite
(22%).
In a separate Phase 3 study of YERVOY 3 mg/kg, the most common
adverse reactions (≥5%) in patients who received YERVOY at
3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%),
rash (29%), and colitis (8%).
Checkmate Trials and Patient
Populations
Checkmate 067 - advanced melanoma alone or in combination
with YERVOY; Checkmate 037 and 066 - advanced melanoma;
Checkmate 017 - squamous non-small cell lung cancer (NSCLC);
Checkmate 057 - non-squamous NSCLC; Checkmate 025 -
renal cell carcinoma; Checkmate 205/039 - classical Hodgkin
lymphoma; Checkmate 141 - squamous cell carcinoma of the
head and neck; Checkmate 275 - urothelial carcinoma.
Please see U.S. Full Prescribing Information for OPDIVO and
YERVOY, including Boxed WARNING regarding immune-mediated
adverse reactions for YERVOY.
About the Bristol-Myers Squibb and Ono
Pharmaceutical Co., Ltd. Collaboration
In 2011, through a collaboration agreement with Ono
Pharmaceutical Co., Ltd (Ono), Bristol-Myers Squibb expanded its
territorial rights to develop and commercialize Opdivo globally
except in Japan, South Korea and Taiwan, where Ono had retained all
rights to the compound at the time. On July 23, 2014, Bristol-Myers
Squibb and Ono further expanded the companies’ strategic
collaboration agreement to jointly develop and commercialize
multiple immunotherapies – as single agents and combination
regimens – for patients with cancer in Japan, South Korea and
Taiwan.
About Empliciti
Empliciti is an immunostimulatory antibody that specifically
targets Signaling Lymphocyte Activation Molecule Family member 7
(SLAMF7), a cell-surface glycoprotein. SLAMF7 is expressed on
myeloma cells independent of cytogenetic abnormalities. SLAMF7 also
is expressed on Natural Killer cells, plasma cells and at lower
levels on specific immune cell subsets of differentiated cells
within the hematopoietic lineage.
Empliciti has a dual mechanism-of-action. It directly activates
the immune system through Natural Killer cells via the SLAMF7
pathway. Empliciti also targets SLAMF7 on myeloma cells, tagging
these malignant cells for Natural Killer cell-mediated destruction
via antibody-dependent cellular toxicity.
On November 30, 2015, the U.S. Food and Drug Administration
(FDA) approved Empliciti in combination with lenalidomide and
dexamethasone in patients with multiple myeloma who have received
one to three prior therapies. On May 11, 2016, the European
Commission approved Empliciti in combination with lenalidomide and
dexamethasone in patients with multiple myeloma who have received
at least one prior therapy. The safety and efficacy of Empliciti is
being evaluated by other health authorities.
Bristol-Myers Squibb and AbbVie are co-developing Empliciti,
with Bristol-Myers Squibb solely responsible for commercial
activities.
U.S. FDA-APPROVED INDICATION FOR
EMPLICITI™
EMPLICITI™ (elotuzumab) is indicated in combination with
lenalidomide and dexamethasone for the treatment of patients with
multiple myeloma who have received one to three prior
therapies.
IMPORTANT SAFETY
INFORMATION
Infusion Reactions
- EMPLICITI can cause infusion reactions.
Common symptoms include fever, chills, and hypertension.
Bradycardia and hypotension also developed during infusions. In the
trial, 5% of patients required interruption of the administration
of EMPLICITI for a median of 25 minutes due to infusion reactions,
and 1% of patients discontinued due to infusion reactions. Of the
patients who experienced an infusion reaction, 70% (23/33) had them
during the first dose. If a Grade 2 or higher infusion reaction
occurs, interrupt the EMPLICITI infusion and institute appropriate
medical and supportive measures. If the infusion reaction recurs,
stop the EMPLICITI infusion and do not restart it on that day.
Severe infusion reactions may require permanent discontinuation of
EMPLICITI therapy and emergency treatment.
- Premedicate with dexamethasone, H1
Blocker, H2 Blocker, and acetaminophen prior to infusing with
EMPLICITI.
Infections
- In a clinical trial of patients with
multiple myeloma (N=635), infections were reported in 81.4% of
patients in the EMPLICITI with lenalidomide/dexamethasone arm (ERd)
and 74.4% in the lenalidomide/dexamethasone arm (Rd). Grade 3-4
infections were 28% (ERd) and 24.3% (Rd). Opportunistic infections
were reported in 22% (ERd) and 12.9% (Rd). Fungal infections were
9.7% (ERd) and 5.4% (Rd). Herpes zoster was 13.5% (ERd) and 6.9%
(Rd). Discontinuations due to infections were 3.5% (ERd) and 4.1%
(Rd). Fatal infections were 2.5% (ERd) and 2.2% (Rd). Monitor
patients for development of infections and treat promptly.
Second Primary Malignancies
- In a clinical trial of patients with
multiple myeloma (N=635), invasive second primary malignancies
(SPM) were 9.1% (ERd) and 5.7% (Rd). The rate of hematologic
malignancies were the same between ERd and Rd treatment arms
(1.6%). Solid tumors were reported in 3.5% (ERd) and 2.2% (Rd).
Skin cancer was reported in 4.4% (ERd) and 2.8% (Rd). Monitor
patients for the development of SPMs.
Hepatotoxicity
- Elevations in liver enzymes (AST/ALT
greater than 3 times the upper limit, total bilirubin greater than
2 times the upper limit, and alkaline phosphatase less than 2 times
the upper limit) consistent with hepatotoxicity were 2.5% (ERd) and
0.6% (Rd). Two patients experiencing hepatotoxicity discontinued
treatment; however, 6 out of 8 patients had resolution and
continued treatment. Monitor liver enzymes periodically. Stop
EMPLICITI upon Grade 3 or higher elevation of liver enzymes. After
return to baseline values, continuation of treatment may be
considered.
Interference with Determination of Complete Response
- EMPLICITI is a humanized IgG kappa
monoclonal antibody that can be detected on both the serum protein
electrophoresis and immunofixation assays used for the clinical
monitoring of endogenous M-protein. This interference can impact
the determination of complete response and possibly relapse from
complete response in patients with IgG kappa myeloma protein.
Pregnancy/Females and Males of Reproductive Potential
- There are no studies with EMPLICITI
with pregnant women to inform any drug associated risks.
- There is a risk of fetal harm,
including severe life-threatening human birth defects associated
with lenalidomide and it is contraindicated for use in pregnancy.
Refer to the lenalidomide full prescribing information for
requirements regarding contraception and the prohibitions against
blood and/or sperm donation due to presence and transmission in
blood and/or semen and for additional information.
Adverse Reactions
- Infusion reactions were reported in
approximately 10% of patients treated with EMPLICITI with
lenalidomide and dexamethasone. All reports of infusion reaction
were Grade 3 or lower. Grade 3 infusion reactions occurred in 1% of
patients.
- Serious adverse reactions were 65.4%
(ERd) and 56.5% (Rd). The most frequent serious adverse reactions
in the ERd arm compared to the Rd arm were: pneumonia (15.4%, 11%),
pyrexia (6.9%, 4.7%), respiratory tract infection (3.1%, 1.3%),
anemia (2.8%, 1.9%), pulmonary embolism (3.1%, 2.5%), and acute
renal failure (2.5%, 1.9%).
- The most common adverse reactions in
ERd and Rd, respectively (>20%) were fatigue (61.6%, 51.7%),
diarrhea (46.9%, 36.0%), pyrexia (37.4%, 24.6%), constipation
(35.5%, 27.1%), cough (34.3%, 18.9%), peripheral neuropathy (26.7%,
20.8%), nasopharyngitis (24.5%, 19.2%), upper respiratory tract
infection (22.6%, 17.4%), decreased appetite (20.8%, 12.6%), and
pneumonia (20.1%, 14.2%).
Please see the full Prescribing Information
for EMPLICITI.
About Sprycel
Sprycel was first approved by the FDA in 2006 for the treatment
of adults with Philadelphia chromosome-positive (Ph+) chronic
myeloid leukemia (CML) in chronic phase (CP) who are resistant or
intolerant to prior therapy including imatinib. At that time,
Sprycel was also approved for adults with Ph+ acute lymphoblastic
leukemia (ALL) who are resistant or intolerant to prior therapy.
Sprycel is approved and marketed worldwide for these indications in
more than 60 countries.
Sprycel is also an FDA-approved treatment for adults with newly
diagnosed CP Ph+ CML (since October 2010). Sprycel received
accelerated FDA approval for this indication. Additional country
approvals for this indication total more than 50.
U.S. FDA-APPROVED INDICATIONS FOR
SPRYCEL®
SPRYCEL® (dasatinib) is indicated for the treatment of
adults with:
- Newly diagnosed adults with
Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia
(CML) in chronic phase.
- Chronic, accelerated, or myeloid or
lymphoid blast phase Ph+ CML with resistance or intolerance to
prior therapy including imatinib.
- Philadelphia chromosome-positive acute
lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to
prior therapy.
IMPORTANT SAFETY
INFORMATION
Myelosuppression
Treatment with SPRYCEL is associated with severe (NCI CTC Grade
3/4) thrombocytopenia, neutropenia, and anemia, which occur earlier
and more frequently in patients with advanced phase CML or Ph+ ALL
than in patients with chronic phase CML. Myelosuppression was
reported in patients with normal baseline laboratory values as well
as in patients with pre-existing laboratory abnormalities.
- In patients with chronic phase CML,
perform complete blood counts (CBCs) every 2 weeks for 12 weeks,
then every 3 months thereafter, or as clinically indicated
- In patients with advanced phase CML or
Ph+ ALL, perform CBCs weekly for the first 2 months and then
monthly thereafter, or as clinically indicated
- Myelosuppression is generally
reversible and usually managed by withholding SPRYCEL temporarily
and/or dose reduction
- In clinical studies, myelosuppression
may have also been managed by discontinuation of study therapy
- Hematopoietic growth factor has been
used in patients with resistant myelosuppression
Bleeding-Related Events
SPRYCEL caused thrombocytopenia in human subjects. In addition,
dasatinib caused platelet dysfunction in vitro. In all CML or
Ph+ ALL clinical studies, ≥grade 3 central nervous system (CNS)
hemorrhages, including fatalities, occurred in <1% of patients
receiving SPRYCEL. Grade 3 or greater gastrointestinal hemorrhage,
including fatalities, occurred in 4% of patients and generally
required treatment interruptions and transfusions. Other cases of
≥grade 3 hemorrhage occurred in 2% of patients.
- Most bleeding events in clinical
studies were associated with severe thrombocytopenia
- Concomitant medications that inhibit
platelet function or anticoagulants may increase the risk of
hemorrhage
Fluid Retention
SPRYCEL may cause fluid retention. After 5 years of follow-up in
the randomized newly diagnosed chronic phase CML study (n=258),
grade 3/4 fluid retention was reported in 5% of patients, including
3% of patients with grade 3/4 pleural effusion. In patients with
newly diagnosed or imatinib resistant or intolerant chronic phase
CML, grade 3/4 fluid retention occurred in 6% of patients treated
with SPRYCEL at the recommended dose (n=548). In patients with
advanced phase CML or Ph+ ALL treated with SPRYCEL at the
recommended dose (n=304), grade 3/4 fluid retention was reported in
8% of patients, including grade 3/4 pleural effusion reported in 7%
of patients.
- Patients who develop symptoms of
pleural effusion or other fluid retention, such as new or worsened
dyspnea on exertion or at rest, pleuritic chest pain, or dry cough
should be evaluated promptly with a chest x-ray or additional
diagnostic imaging as appropriate
- Fluid retention events were typically
managed by supportive care measures that may include diuretics or
short courses of steroids
- Severe pleural effusion may require
thoracentesis and oxygen therapy
- Consider dose reduction or treatment
interruption
Cardiovascular Events
After 5 years of follow-up in the randomized newly diagnosed
chronic phase CML trial (n=258), the following cardiac adverse
events occurred:
- Cardiac ischemic events (3.9% dasatinib
vs 1.6% imatinib), cardiac related fluid retention (8.5% dasatinib
vs 3.9% imatinib), and conduction system abnormalities, most
commonly arrhythmia and palpitations (7.0% dasatinib vs 5.0%
imatinib). Two cases (0.8%) of peripheral arterial occlusive
disease occurred with imatinib and 2 (0.8%) transient ischemic
attacks occurred with dasatinib
Monitor patients for signs or symptoms consistent with cardiac
dysfunction and treat appropriately.
Pulmonary Arterial Hypertension (PAH)
SPRYCEL may increase the risk of developing PAH, which may occur
any time after initiation, including after more than 1 year of
treatment. Manifestations include dyspnea, fatigue, hypoxia, and
fluid retention. PAH may be reversible on discontinuation of
SPRYCEL.
- Evaluate patients for signs and
symptoms of underlying cardiopulmonary disease prior to initiating
SPRYCEL and during treatment. If PAH is confirmed, SPRYCEL should
be permanently discontinued
QT Prolongation
In vitro data suggest that dasatinib has the potential to
prolong cardiac ventricular repolarization (QT interval).
- In clinical trials of patients treated
with SPRYCEL at all doses (n=2440), 16 patients (<1%) had
QTc prolongation reported as an adverse reaction. Twenty-two
patients (1%) experienced a QTcF >500 ms
- In 865 patients with leukemia treated
with SPRYCEL in five Phase 2 single-arm studies, the maximum mean
changes in QTcF (90% upper bound CI) from baseline ranged from 7.0
to 13.4 ms
- SPRYCEL may increase the risk of
prolongation of QTc in patients including those with hypokalemia or
hypomagnesemia, patients with congenital long QT syndrome, patients
taking antiarrhythmic medicines or other medicinal products that
lead to QT prolongation, and cumulative high-dose anthracycline
therapy
- Correct hypokalemia or hypomagnesemia
prior to and during SPRYCEL administration
Severe Dermatologic Reactions
Cases of severe mucocutaneous dermatologic reactions, including
Stevens-Johnson syndrome and erythema multiforme, have been
reported in patients treated with SPRYCEL.
- Discontinue permanently in patients who
experience a severe mucocutaneous reaction during treatment if no
other etiology can be identified
Tumor Lysis Syndrome (TLS)
TLS has been reported in patients with resistance to prior
imatinib therapy, primarily in advanced phase disease.
- Due to potential for TLS, maintain
adequate hydration, correct uric acid levels prior to initiating
therapy with SPRYCEL, and monitor electrolyte levels
- Patients with advanced stage disease
and/or high tumor burden may be at increased risk and should be
monitored more frequently
Embryo-Fetal Toxicity
Based on limited human data, SPRYCEL can cause fetal harm when
administered to a pregnant woman. Hydrops fetalis, fetal leukopenia
and fetal thrombocytopenia have been reported with maternal
exposure to SPRYCEL. Transplacental transfer of dasatinib has been
measured in fetal plasma and amniotic fluid at concentrations
comparable to those in maternal plasma.
- Advise females of reproductive
potential to avoid pregnancy, which may include the use of
effective contraception, during treatment with SPRYCEL and for 30
days after the final dose
Lactation
No data are available regarding the presence of dasatinib in
human milk, the effects of the drug on the breastfed infant or the
effects of the drug on milk production. However, dasatinib is
present in the milk of lactating rats.
- Because of the potential for serious
adverse reactions in nursing infants from SPRYCEL, breastfeeding is
not recommended during treatment with SPRYCEL and for 2 weeks after
the final dose
Drug Interactions
SPRYCEL is a CYP3A4 substrate and a weak time-dependent
inhibitor of CYP3A4.
- Drugs that
may increase SPRYCEL plasma concentrations are:
- CYP3A4
inhibitors: Concomitant use of SPRYCEL and drugs that
inhibit CYP3A4 should be avoided. If administration of a potent
CYP3A4 inhibitor cannot be avoided, close monitoring for toxicity
and a SPRYCEL dose reduction should be considered
- Strong CYP3A4
inhibitors (eg, ketoconazole, itraconazole,
clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir,
ritonavir, saquinavir, telithromycin, voriconazole). If SPRYCEL
must be administered with a strong CYP3A4 inhibitor, a dose
decrease or temporary discontinuation should be considered
- Grapefruit juice may also
increase plasma concentrations of SPRYCEL and should be
avoided
- Drugs that
may decrease SPRYCEL plasma concentrations are:
- CYP3A4 inducers: If SPRYCEL must
be administered with a CYP3A4 inducer, a dose increase in SPRYCEL
should be considered
- Strong CYP3A4 inducers (eg,
dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin,
phenobarbital) should be avoided. Alternative agents with less
enzyme induction potential should be considered. If the dose of
SPRYCEL is increased, the patient should be monitored carefully for
toxicity
- St John’s Wort may decrease
SPRYCEL plasma concentrations unpredictably and should be
avoided
- Antacids may decrease
SPRYCEL drug levels. Simultaneous administration of SPRYCEL and
antacids should be avoided. If antacid therapy is needed, the
antacid dose should be administered at least 2 hours prior to or 2
hours after the dose of SPRYCEL
-
H 2 antagonists/proton pump
inhibitors (eg, famotidine and omeprazole): Long-term
suppression of gastric acid secretion by use of H2 antagonists
or proton pump inhibitors is likely to reduce SPRYCEL exposure.
Therefore, concomitant use of H2 antagonists or proton pump
inhibitors with SPRYCEL is not recommended
- Drugs that may have their plasma
concentration altered by SPRYCEL are:
- CYP3A4 substrates (eg,
simvastatin) with a narrow therapeutic index should be administered
with caution in patients receiving SPRYCEL
Adverse Reactions
The safety data reflects exposure to SPRYCEL at all doses tested
in clinical studies including 324 patients with newly diagnosed
chronic phase CML and 2388 patients with imatinib resistant or
intolerant chronic or advanced phase CML or Ph+ ALL.
The median duration of therapy in all 2712 SPRYCEL-treated
patients was 19.2 months (range 0–93.2 months). Median duration of
therapy in:
- 1618 patients with chronic phase CML
was 29 months (range 0–92.9 months)
- Median duration for 324 patients in the
newly diagnosed chronic phase CML trial was approximately 60
months
- 1094 patients with advanced phase CML
or Ph+ ALL was 6.2 months (range 0–93.2 months)
In the newly diagnosed chronic phase CML trial, after a minimum
of 60 months of follow-up, the cumulative discontinuation rate for
258 patients was 39%.
In the overall population of 2712 SPRYCEL-treated patients, 88%
of patients experienced adverse reactions at some time and 19%
experienced adverse reactions leading to treatment
discontinuation.
Among the 1618 SPRYCEL-treated patients with chronic phase CML,
drug-related adverse events leading to discontinuation were
reported in 329 (20.3%) patients.
- In the newly diagnosed chronic phase
CML trial, drug was discontinued for adverse reactions in 16% of
SPRYCEL-treated patients with a minimum of 60 months of
follow-up
Among the 1094 SPRYCEL-treated patients with advanced phase CML
or Ph+ ALL, drug-related adverse events leading to discontinuation
were reported in 191 (17.5%) patients.
Patients ≥65 years are more likely to experience the commonly
reported adverse reactions of fatigue, pleural effusion, diarrhea,
dyspnea, cough, lower gastrointestinal hemorrhage, and appetite
disturbance, and more likely to experience the less frequently
reported adverse reactions of abdominal distention, dizziness,
pericardial effusion, congestive heart failure, hypertension,
pulmonary edema and weight decrease, and should be monitored
closely.
- In newly diagnosed chronic phase CML
patients:
- Drug-related serious adverse events
(SAEs) were reported for 16.7% of SPRYCEL-treated patients. Serious
adverse reactions reported in ≥5% of patients included pleural
effusion (5%)
- The most common adverse reactions
(≥15%) included myelosuppression, fluid retention, and
diarrhea
- Grade 3/4 laboratory abnormalities
included neutropenia (29%), thrombocytopenia (22%), anemia (13%),
hypophosphatemia (7%), hypocalcemia (4%), elevated bilirubin (1%),
and elevated creatinine (1%)
- In patients resistant or intolerant to
prior imatinib therapy:
- Drug-related SAEs were reported for
26.1% of SPRYCEL-treated patients treated at the recommended dose
of 100 mg once daily in the randomized dose-optimization trial of
patients with chronic phase CML resistant or intolerant to prior
imatinib therapy. Serious adverse reactions reported in ≥5% of
patients included pleural effusion (10%)
- The most common adverse reactions
(≥15%) included myelosuppression, fluid retention events, diarrhea,
headache, fatigue, dyspnea, skin rash, nausea, hemorrhage and
musculoskeletal pain
- Grade 3/4 hematologic laboratory
abnormalities in chronic phase CML patients resistant or intolerant
to prior imatinib therapy who received SPRYCEL 100 mg once daily
with a minimum follow up of 60 months included neutropenia (36%),
thrombocytopenia (24%), and anemia (13%). Other grade 3/4
laboratory abnormalities included: hypophosphatemia (10%), and
hypokalemia (2%)
- Among chronic phase CML patients with
resistance or intolerance to prior imatinib therapy, cumulative
grade 3/4 cytopenias were similar at 2 and 5 years including:
neutropenia (36% vs 36%), thrombocytopenia (23% vs 24%), and anemia
(13% vs 13%)
- Grade 3/4 elevations of transaminases
or bilirubin and Grade 3/4 hypocalcemia, hypokalemia, and
hypophosphatemia were reported in patients with all phases of CML
- Elevations in transaminases or
bilirubin were usually managed with dose reduction or
interruption
- Patients developing Grade 3/4
hypocalcemia during the course of SPRYCEL therapy often had
recovery with oral calcium supplementation
Please see the full Prescribing Information for SPRYCEL.
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
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Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that
term is defined in the Private Securities Litigation Reform Act of
1995 regarding the research, development and commercialization of
pharmaceutical products. Such forward-looking statements are based
on current expectations and involve inherent risks and
uncertainties, including factors that could delay, divert or change
any of them, and could cause actual outcomes and results to differ
materially from current expectations. No forward-looking statement
can be guaranteed. Among other risks, there can be no guarantee
that any of the oncology compounds mentioned in this release will
receive regulatory approval for an additional indication.
Forward-looking statements in this press release should be
evaluated together with the many uncertainties that affect
Bristol-Myers Squibb's business, particularly those identified in
the cautionary factors discussion in Bristol-Myers Squibb's Annual
Report on Form 10-K for the year ended December 31, 2016, in our
Quarterly Reports on Form 10-Q and our Current Reports on Form
8-K. Bristol-Myers Squibb undertakes no obligation to publicly
update any forward-looking statement, whether as a result of new
information, future events or otherwise.
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version on businesswire.com: http://www.businesswire.com/news/home/20170517006335/en/
Bristol-Myers SquibbMedia:Audrey Abernathy,
919-605-4521audrey.abernathy@bms.comorRose Weldon,
215-801-7644rose.weldon@bms.comorInvestors:Bill Szablewski,
609-252-5894william.szablewski@bms.comorTim Power,
609-252-7509timothy.power@bms.com
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