INDIANAPOLIS, April 20, 2015 /PRNewswire/ -- Eli Lilly and
Company (NYSE: LLY) will present early stage data from several
targeted cancer therapies, reflecting Lilly's diverse oncology
pipeline, during the American Association for Cancer Research
(AACR) Annual Meeting 2015, held April
18-22 in Philadelphia,
Pa.
"Bringing Cancer Discoveries to Patients" is the theme of this
year's AACR meeting and one that is mirrored through Lilly's
commitment to broadening its portfolio of therapies that accelerate
the pace and progress of cancer care. Lilly research to be
presented at AACR represents findings from several of its oncology
pipeline compounds in various stages of development.
"The research we present at AACR will set the stage for the next
generation of therapies from Lilly," said Richard Gaynor, M.D., senior vice president of
product development and medical affairs for Lilly Oncology. "Each
step we take in the course of our research—both in the lab and in
clinical trials—leads us toward the same overall goal: to increase
the number of life-changing medicines and innovative solutions
available to patients."
Abstract #3101: In-vitro characterization of abemaciclib
pharmacology in ER+ breast cancer cell lines
Presentation
date: April 21, 2015, 8:00 AM – 12:00
PM
Authors: Lallena, M.J.; Torres, R.;
et.al.
Cyclin-dependent kinases play a key role in
regulating cell-cycle progression. In many cancers, there is a loss
of control in regulating the cell cycle in response to increased
signaling from CDK4/6. As a result there is uncontrolled growth of
cancer cells. Lilly's abemaciclib (LY2835219) is a cell-cycle
inhibitor, designed to block the growth of cancer cells by
specifically inhibiting CDK 4 and 6. Preclinical and early-stage
clinical evaluation indicates that Lilly's abemaciclib may have
potential therapeutic application for the treatment of human
cancers—including breast cancer—in which an aberrant CDK4/6 pathway
enhances cancer cell growth.
Lilly researchers have thoroughly investigated the mechanism of
action of abemaciclib in estrogen receptor positive (ER+) luminal
breast cancer cells. A diversity of breast cancer cell lines showed
marked sensitivity to treatment with abemaciclib. Phenotypic and
cell-fate characterization was conducted by monitoring
proliferation, cell-cycle arrest, retinoblastoma (Rb)
phosphorylation, senescence response (the loss of a cell's ability
to divide), apoptosis (programmed cell death) and cell metabolism
profile. The study identified three distinct mechanisms of action
when luminal ER+ breast cancer cells are treated with abemaciclib
at relevant pharmacological concentrations: potent cell-cycle
arrest, efficient senescence response and induction of metabolic
alterations.
Abemaciclib has now entered Phase III development in hormone
receptor positive breast cancer patients.
Abstract #CT240: Checkpoint Kinase (CHK) 1/2 Inhibitor
LY2606368 in a Phase I Dose-Expansion Study in Patients with
Squamous Cell Carcinoma of the Head and Neck
Presentation
date: April 20, 2015, 4:30
– 4:50
PM
Authors: Bendell, J.; Grant, S.; Janku F.;
et.al.
Checkpoint kinase 1 (CHK1) regulates DNA damage
checkpoints, and also plays a central role in normal DNA
replication, mitosis (when a cell divides into an identical,
replicated cell) and cytokinesis (the process by which a cell
divides). Inhibition of CHK1 can cause impaired DNA replication,
loss of DNA damage checkpoints, a cell's premature entry into
mitosis, mitotic catastrophe and cell death. LY2606368 is a small
molecule that has been observed, in vitro, to preferentially
bind to and inhibit CHK1 and, to a lesser extent, CHK2, thus
inducing DNA double-strand breaks, a loss in DNA checkpoint
function and cell death.
LY2606368 was evaluated in this Phase I, multicenter,
non-randomized, open-label study in patients with advanced cancer.
For this cohort, based on results from the dose-escalation phase,
patients with recurrent or metastatic squamous cell carcinoma of
the head and neck (SCCHN) were treated with single-agent LY2606368
(105 mg/m2) on day one of a 14-day cycle.
The trial enrollment included 57 patients with recurrent or
metastatic SCCHN with more than half of those receiving at least
two prior lines of treatment (median of three cycles; range 1-5) in
the recurrent/metastatic setting. Twenty-five patients (44%)
achieved stable disease and three patients (5%) achieved a partial
response for at least three treatment cycles. The duration of
patient response ranged from 4.8-7.8 months and the median
progression-free survival (PFS) was 1.6 months (90% CI: 1.4, 2.8).
Pretreatment biopsy samples from 34 patients were evaluated for
pharmacogenomic analysis, including human papillomavirus (HPV)
status. Patients who were HPV positive (n=15) achieved 4.5 months
of median PFS while HPV-negative patients (n=19) achieved 1.4
months median PFS.
The most frequently reported adverse event was a transient
decrease in neutrophil/leukocyte count (91%). Grade 4 neutropenia
occurred in 63 percent of patients, but was transient (typically
less than five days). Febrile neutropenia was identified in 10
patients (18%). Other treatment-related adverse events occurring in
greater than 10 percent of patients included thrombocytopenia
(44%), anemia (25%), fatigue (23%) and headache (14%). The majority
of non-hematologic adverse events were identified as grades 1 or
2.
LY2606368 is now entering Phase II development.
Abstract #2142: Novel Oncogenic BRaf Deletions Functioning as
BRaf Homodimer and Sensitive to Inhibition by LY3009120, a Pan Raf
and Raf Dimer Inhibitor
Presentation date: April 20, 2015, 1:00 – 5:00 PM
Authors: Chen, S.; Buchanan,
S.; Zhang, Y.; et.al.
BRAF genetic mutations have been
identified in many cancer types with BRAF V600E, a specific potent
oncogene that activates the MAPK pathway and functions as a BRAF
monomer. Several BRAF selective inhibitors have demonstrated
efficacy in the inhibition of the BRAF monomer kinase activity, but
no compound to date has demonstrated efficacy on non-BRAF V600E
mutations, which generally function as a RAF dimer.
This study identified and characterized novel BRAF variants,
which have in-frame deletions within or adjacent to the L485-P490
region in patient samples and/or cell lines of lung, pancreatic and
ovarian cancers. These BRAF in-frame deletions function as a BRAF
homodimer. Tumor cells with these BRAF deletions are resistant to
BRAF monomer inhibitors. However, preclinical evaluation has shown
Lilly's pan-RAF and RAF dimer inhibitor, LY3009120, to be active to
these cells. In the study, lung and pancreatic cancer xenograft
models developed with BRAF deletion tumor cells demonstrated
significant tumor growth inhibition and regression when treated
with LY3009120.
These findings, and other preclinical research, have advanced
LY3009120 to Phase I of clinical development.
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
newsroom.lilly.com/social-channels.
P-LLY
This press release contains forward-looking statements about
the potential of abemaciclib, LY2606368 and LY3009120 as potential
treatments for several types of cancer and reflects Lilly's current
beliefs. However, as with any pharmaceutical products, there are
substantial risks and uncertainties in the process of development
and commercialization. There can be no guarantee that future study
results and patient experience will be consistent with the study
findings to date. There can also be no guarantee that these
compounds will receive regulatory approval for any future
indications or that they will prove to be commercially successful.
For further discussion of these and other risks and uncertainties
that could cause actual results to differ 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.
Refer
To:
|
Carla Cox (Lilly
Oncology); cox_carla_l@lilly.com; (317) 473-4368
(mobile)
|
|
Neil Hochman
(TogoRun); n.hochman@togorun.com; (212) 453-2067 (office); (516)
784-9089 (mobile);
|
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SOURCE Eli Lilly and Company