Bristol-Myers Squibb Company (NYSE:BMY) and Eli Lilly and
Company (NYSE:LLY) announced today a clinical trial collaboration
to evaluate the safety, tolerability and preliminary efficacy of
Bristol-Myers Squibb’s immunotherapy Opdivo (nivolumab) in
combination with Lilly’s galunisertib (LY2157299). The Phase 1/2
trial will evaluate the investigational combination of Opdivo and
galunisertib as a potential treatment option for patients with
advanced (metastatic and/or unresectable) glioblastoma,
hepatocellular carcinoma and non-small cell lung cancer.
Opdivo is a human programmed death receptor-1 (PD-1) blocking
antibody that binds to the PD-1 receptor expressed on activated
T-cells. Galunisertib (pronounced gal ue" ni ser'tib) is a TGF beta
R1 kinase inhibitor that in vitro selectively blocks TGF beta
signaling. TGF beta promotes tumor growth, suppresses the immune
system and increases the ability of tumors to spread in the body.
This collaboration will address the hypothesis that co-inhibition
of PD-1 and TGF beta negative signals may lead to enhanced
anti-tumor immune responses than inhibition of either pathway
alone.
“Advanced solid tumors represent a serious unmet medical need
among patients with cancer,” said Michael Giordano, senior vice
president, Head of Development, Oncology, Bristol-Myers Squibb.
“Our clinical collaboration with Lilly underscores Bristol-Myers
Squibb’s continued commitment to explore combination regimens from
our immuno-oncology portfolio with other mechanisms of action that
may accelerate the development of new treatment options for
patients.”
“Combination therapies will be key to addressing tumor
heterogeneity and the inevitable resistance that is likely to
develop to even the most promising new tailored therapies,” said
Richard Gaynor, M.D., senior vice president, Product Development
and Medical Affairs, Lilly Oncology. “To that end, having multiple
cancer pathways and technology platforms will be critical in an era
of combinations to ensure sustainability beyond any single
asset.”
The study will be conducted by Lilly. Additional details of the
collaboration were not disclosed.
About Opdivo (nivolumab)
The U.S. Food and Drug Administration (FDA) approved Opdivo
(nivolumab) injection, for intravenous use. Opdivo is a
PD-1 blocking antibody indicated for the treatment of patients with
unresectable or metastatic melanoma and disease progression
following Yervoy (ipilimumab) and, if BRAF V600 mutation
positive, a BRAF inhibitor. This indication is approved under
accelerated approval based on tumor response rate and durability of
response. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in the
confirmatory trials. Bristol-Myers Squibb has a broad, global
development program to study Opdivo in multiple tumor
types consisting of more than 50 trials – as monotherapy or in
combination with other therapies – in which more than 7,000
patients have been enrolled worldwide.
About Galunisertib
Galunisertib (pronounced gal ue" ni ser'tib) is Lilly’s TGF beta
R1 kinase inhibitor that in vitro selectively blocks TGF beta
signaling. TGF beta promotes tumors growth, suppresses the immune
system, and increases the ability of tumors to spread in the
body.
Immune function is suppressed in cancer patients, and TGF beta
worsens immunosuppression by enhancing the activity of immune cells
called T regulatory cells. TGF beta also reduces immune
proteins, further decreasing immune activity in patients
Galunisertib is currently under investigation as an oral
treatment for advanced/metastatic malignancies, including Phase 2
evaluation in hepatocellular carcinoma, myelodysplastic syndromes
(MDS), glioblastoma, and pancreatic cancer.
OPDIVO IMPORTANT SAFETY INFORMATION
Immune-Mediated Pneumonitis
- Severe pneumonitis or interstitial lung
disease, including fatal cases, occurred with OPDIVO treatment.
Across the clinical trial experience in 574 patients with solid
tumors, fatal immune-mediated pneumonitis occurred in 0.9% (5/574)
of patients receiving OPDIVO; no cases occurred in Trial 1. In
Trial 1, pneumonitis, including interstitial lung disease, occurred
in 3.4% (9/268) of patients receiving OPDIVO and none of the 102
patients receiving chemotherapy. Immune-mediated pneumonitis
occurred in 2.2% (6/268) of patients receiving OPDIVO; one with
Grade 3 and five with Grade 2. Monitor patients for signs and
symptoms of pneumonitis. Administer corticosteroids for Grade 2 or
greater pneumonitis. Permanently discontinue OPDIVO for Grade 3 or
4 and withhold OPDIVO until resolution for Grade 2.
Immune-Mediated Colitis
- In Trial 1, diarrhea or colitis
occurred in 21% (57/268) of patients receiving OPDIVO and 18%
(18/102) of patients receiving chemotherapy. Immune-mediated
colitis occurred in 2.2% (6/268) of patients receiving OPDIVO; five
with Grade 3 and one with Grade 2. Monitor patients for
immune-mediated colitis. Administer corticosteroids for Grade 2 (of
more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO for
Grade 2 or 3. Permanently discontinue OPDIVO for Grade 4 colitis or
recurrent colitis upon restarting OPDIVO.
Immune-Mediated Hepatitis
- In Trial 1, there was an increased
incidence of liver test abnormalities in the OPDIVO-treated group
as compared to the chemotherapy-treated group, with increases in
AST (28% vs 12%), alkaline phosphatase (22% vs 13%), ALT (16% vs
5%), and total bilirubin (9% vs 0). Immune-mediated hepatitis
occurred in 1.1% (3/268) of patients receiving OPDIVO; two with
Grade 3 and one with Grade 2. Monitor patients for abnormal liver
tests prior to and periodically during treatment. Administer
corticosteroids for Grade 2 or greater transaminase elevations.
Withhold OPDIVO for Grade 2 and permanently discontinue OPDIVO for
Grade 3 or 4 immune-mediated hepatitis.
Immune-Mediated Nephritis and Renal Dysfunction
- In Trial 1, there was an increased
incidence of elevated creatinine in the OPDIVO-treated group as
compared to the chemotherapy-treated group (13% vs 9%). Grade 2 or
3 immune-mediated nephritis or renal dysfunction occurred in 0.7%
(2/268) of patients. Monitor patients for elevated serum creatinine
prior to and periodically during treatment. For Grade 2 or 3 serum
creatinine elevation, withhold OPDIVO and administer
corticosteroids; if worsening or no improvement occurs, permanently
discontinue OPDIVO. Administer corticosteroids for Grade 4 serum
creatinine elevation and permanently discontinue OPDIVO.
Immune-Mediated Hypothyroidism and Hyperthyroidism
- In Trial 1, Grade 1 or 2 hypothyroidism
occurred in 8% (21/268) of patients receiving OPDIVO and none of
the 102 patients receiving chemotherapy. Grade 1 or 2
hyperthyroidism occurred in 3% (8/268) of patients receiving OPDIVO
and 1% (1/102) of patients receiving chemotherapy. Monitor thyroid
function prior to and periodically during treatment. Administer
hormone replacement therapy for hypothyroidism. Initiate medical
management for control of hyperthyroidism.
Other Immune-Mediated Adverse Reactions
- In Trial 1, the following clinically
significant, immune-mediated adverse reactions occurred in less
than 1% of OPDIVO-treated patients: pancreatitis, uveitis,
demyelination, autoimmune neuropathy, adrenal insufficiency, and
facial and abducens nerve paresis. Across clinical trials of OPDIVO
administered at doses 3 mg/kg and 10 mg/kg, additional clinically
significant, immune-mediated adverse reactions were identified:
hypophysitis, diabetic ketoacidosis, hypopituitarism,
Guillian-Barré syndrome, and myasthenic syndrome. Based on the
severity of adverse reaction, withhold OPDIVO, administer high-dose
corticosteroids, and, if appropriate, initiate hormone-replacement
therapy.
Embryofetal Toxicity
- Based on its mechanism of action,
OPDIVO 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 OPDIVO and for at least 5 months after the
last dose of OPDIVO.
Lactation
- It is not known whether OPDIVO 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 OPDIVO, advise women to
discontinue breastfeeding during treatment.
Serious Adverse Reactions
- Serious adverse reactions occurred in
41% of patients receiving OPDIVO. 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.
Common Adverse Reactions
The most common adverse reaction (≥20%) reported with OPDIVO was
rash (21%).
Please see US Full Prescribing
Information for OPDIVO.
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, please visit www.bms.com or follow us on Twitter at
http://twitter.com/bmsnews.
About Lilly Oncology
For more than fifty years, Lilly has been dedicated to
delivering life-changing medicines and support to people living
with cancer and those who care for them. Lilly is determined to
build on this heritage and continue making life better for all
those affected by cancer around the world. To learn more about
Lilly's commitment to people with cancer, please visit
www.LillyOncology.com.
About Eli Lilly and Company
Lilly is a global healthcare leader that unites caring with
discovery to make life better for people around the world. We were
founded more than a century ago by a man committed to creating
high-quality medicines that meet real needs, and today we remain
true to that mission in all our work. Across the globe, Lilly
employees work to discover and bring life-changing medicines to
those who need them, improve the understanding and management of
disease, and give back to communities through philanthropy and
volunteerism. To learn more about Lilly, please visit us at
www.lilly.com and http://newsroom.lilly.com/social-channels.
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 this investigational combination regimen will receive
regulatory approval, or, if approved, that it will become a
commercially successful product. 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, 2013 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.
Lilly Forward-Looking Statement
This press release contains “forward-looking statements” (as
that term is defined in the United States Private Securities
Litigation Reform Act of 1995) regarding the research collaboration
between Bristol-Myers Squibb and Lilly. This press release reflects
Lilly's current beliefs. However, there are substantial risks and
uncertainties in the process of drug research, development, and
commercialization. Among other risks, there can be no guarantee
that this investigational combination regimen will receive
regulatory approval, or, if approved, that it will achieve intended
benefits or become a commercially successful product. For further
discussion of these and other risks and uncertainties that could
cause actual results to differ materially from Lilly's
expectations, please see the company's latest Forms 10-K and 10-Q
filed with the U.S. Securities and Exchange Commission. Except as
required by law, Lilly undertakes no duty to update forward-looking
statements.
P-LLY
Bristol-Myers SquibbMedia:Ken Dominski,
609-252-5251ken.dominski@bms.comorInvestors:Ranya Dajani,
609-252-5330ranya.dajani@bms.comorRyan Asay,
609-252-5020ryan.asay@bms.comorLillyEli Lilly and
CompanyKeri McGrath Happe, +1-317-277-3768Communications
Managermcgrath_happeks@lilly.com
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