Data demonstrated promising monotherapy
activity with olomorasib across a range of KRAS G12C-mutant solid
tumors, including non-small cell lung cancer, and a tolerability
profile in combination with pembrolizumab that is well-suited to
first-line lung cancer development
INDIANAPOLIS, June 1, 2024
/PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced
updated data from the Phase 1/2 clinical trial evaluating
olomorasib as a monotherapy in patients with KRAS
G12C-mutant advanced solid tumors and in combination with Merck's
anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in patients
with KRAS G12C-mutant advanced non-small cell lung cancer
(NSCLC). Olomorasib is an investigational, oral, potent, and highly
selective second-generation inhibitor of the KRAS
G12C protein. These data will be shared in oral presentations
at the 2024 American Society of Clinical Oncology (ASCO) Annual
Meeting.
"Despite recent advances, there remains a significant unmet need
for patients with KRAS G12C-mutant cancers," said
Timothy Burns, M.D., Ph.D.,
Associate Professor of Medicine, University of
Pittsburgh Medical Center Hillman Cancer Center. "These data
show efficacy with olomorasib across tumor types and, importantly,
tolerability that suggests it can be combined with immunotherapy,
the backbone of first-line treatment for KRAS-mutant NSCLC.
In NSCLC, it is also exciting to see promising activity in patients
previously treated with a KRAS G12C inhibitor as well as central
nervous system (CNS) activity, consistent with the improved potency
of this second generation KRAS G12C inhibitor. Collectively, these
data point to a promising emerging profile for olomorasib,
particularly in NSCLC where new options are needed to improve
outcomes for patients."
"As a second generation KRAS G12C inhibitor, olomorasib was
specifically designed to offer a differentiated profile that could
potentially overcome limitations of currently available treatment
options," said David Hyman, M.D.,
chief medical officer, Lilly. "With these updated data, we are
pleased to see our thesis for olomorasib continuing to translate
clinically. Through our SUNRAY-01 study, we look forward to further
investigating the potential of olomorasib in combination with
pembrolizumab-containing regimens in first-line NSCLC, where there
remains great need to further impact the disease trajectory for
patients with KRAS G12C-mutant lung cancers."
Data from the LOXO-RAS-20001 Phase 1/2 Study
Results
presented at ASCO utilized a cutoff date of March 18, 2024. Efficacy results are based on
investigator response assessments, and objective response rates
(ORR) include responses that are confirmed, as well as those
pending confirmation and ongoing.
Olomorasib as Monotherapy in KRAS G12C-Mutant Advanced Solid
Tumors
An oral presentation (abstract #3007) detailed updated data
for olomorasib monotherapy in patients with KRAS
G12C-mutant advanced solid tumors. This dataset consisted of
184 patients, including 42 with NSCLC naïve to a KRAS G12C
inhibitor (six with active brain metastases), 41 with NSCLC
who had received a prior KRAS G12C inhibitor, 32 with colorectal
cancer (CRC), 24 with pancreatic cancer, and 45 with other solid
tumors. Patients had received a median of three prior lines of
therapy (range 0-11).
Efficacy for olomorasib monotherapy was consistent across a
range of solid tumors with an ORR of 35% (37/105) in patients with
non-CRC solid tumors. Median progression free survival (PFS) in all
patients with KRAS G12C inhibitor-naive non-CRC solid tumors was
7.1 months (95% CI: 5.5-8.9) and 7.9 months (95% CI: 4.1-NE) in
patients with KRAS G12C inhibitor-naive NSCLC. In patients with
NSCLC previously treated with a KRAS G12C inhibitor, the ORR was
41% (16/39), with 63% having received a KRAS G12C inhibitor as
their immediate prior therapy, and median PFS was 8.1 months (95%
CI: 5.6-15.6). Preliminary CNS activity was seen, with CNS
responses observed in patients with NSCLC and measurable brain
metastases.
Patients were on treatment for a median of 4.7 months and
treatment-related adverse events (TRAEs) were predominantly grade 1
with only diarrhea seen in greater than 15% of patients. The most
common TRAEs of any grade were diarrhea (23%), nausea (11%), and
fatigue (10%). The safety profile for patients
who discontinued a prior KRAS G12C inhibitor due to toxicity
was similar to all patients treated with olomorasib
monotherapy including patients who discontinued their previous
first KRAS G12C inhibitor due to toxicity. TRAEs led to
discontinuation of olomorasib in 1% of patients.
Olomorasib in Combination with Pembrolizumab in KRAS
G12C-Mutant Advanced NSCLC
An oral presentation (abstract #8510) detailed updated data for
olomorasib in combination with pembrolizumab in patients with
KRAS G12C-mutant advanced NSCLC, studying the two doses
(50mg and 100mg BID) under ongoing investigation in first-line
NSCLC. This dataset consisted of 64 patients, including patients
with first-line metastatic disease and those previously treated
(prior KRAS G12C inhibitor, chemotherapy, and/or
immunotherapy). Patients received a median of two prior lines of
therapy (range: 0-8).
In patients with first-line metastatic NSCLC, across a range of
PD-L1 levels, the ORR for olomorasib in combination with
pembrolizumab was 77% (13/17) and median PFS was not
reached with follow-up ongoing. The most common TRAEs of
any grade were diarrhea (23%), increased ALT (20%),
pruritus (19%), increased AST (16%), and fatigue (16%). TRAEs led
to discontinuation of olomorasib only in 3% of patients (2/64),
pembrolizumab only in 11% of patients (7/64) and both drugs in 5%
of patients (3/64).
The SUNRAY-01 trial (NCT06119581), a global, registrational
study investigating olomorasib in combination with pembrolizumab or
pembrolizumab plus chemotherapy in first-line NSCLC, is currently
enrolling.
KEYTRUDA® is a registered trademark of Merck Sharp
& Dohme LLC, a subsidiary of Merck & Co., Inc.,
Rahway, NJ, USA.
About the LOXO-RAS-20001 Study
LOXO-RAS-20001 is an
open-label, multicenter, Phase 1/2 study evaluating the safety,
tolerability and preliminary efficacy of olomorasib in patients
with KRAS G12C-mutant advanced solid tumors (NCT04956640).
The study includes a Phase 1a dose escalation phase of olomorasib
monotherapy in KRAS G12C-mutant solid tumors and a
Phase 1b dose expansion and
optimization phase which are evaluating olomorasib as a monotherapy
and in combination with other treatments.
About Olomorasib
Olomorasib (LY3537982) is an
investigational, oral, potent, and highly selective
second-generation inhibitor of the KRAS G12C protein. KRAS
is the most common oncogene across all tumor types, and KRAS
G12C mutations occur in 13% of patients with non-small cell lung
cancer (NSCLC) and 1-3% of patients with other solid
tumors.1,2 Olomorasib was specifically designed to
target KRAS G12C mutations and has pharmacokinetic
properties which allow for high predicted target occupancy and high
potency when used as monotherapy or in combination.3
Olomorasib is currently being studied in the LOXO-RAS-20001
Phase 1/2 trial (NCT04956640) in patients with KRAS
G12C-mutant NSCLC and other advanced solid tumors and in the
pivotal, registrational SUNRAY-01 global study (NCT06119581)
investigating olomorasib in combination with pembrolizumab with or
without chemotherapy for first-line treatment of KRAS
G12C-mutant advanced NSCLC. For additional information about
olomorasib clinical trials, please refer to clinicaltrials.gov.
About Lilly
Lilly is a medicine company turning
science into healing to make life better for people around the
world. We've been pioneering life-changing discoveries for nearly
150 years, and today our medicines help more than 51 million people
across the globe. Harnessing the power of biotechnology, chemistry
and genetic medicine, our scientists are urgently advancing new
discoveries to solve some of the world's most significant health
challenges: redefining diabetes care; treating obesity and
curtailing its most devastating long-term effects; advancing the
fight against Alzheimer's disease; providing solutions to some of
the most debilitating immune system disorders; and transforming the
most difficult-to-treat cancers into manageable diseases. With each
step toward a healthier world, we're motivated by one thing: making
life better for millions more people. That includes delivering
innovative clinical trials that reflect the diversity of our world
and working to ensure our medicines are accessible and affordable.
To learn more, visit Lilly.com and Lilly.com/news, or follow
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© Lilly USA, LLC 2024. ALL
RIGHTS RESERVED.
Cautionary Statement Regarding Forward-Looking
Statements
This press release contains forward-looking
statements (as that term is defined in the Private Securities
Litigation Reform Act of 1995) about olomorasib as a potential
treatment for people with certain KRAS G12C-mutant
advanced solid tumors and reflects Lilly's current beliefs and
expectations. However, as with any pharmaceutical product, there
are substantial risks and uncertainties in the process of drug
research, development, and commercialization. Among other things,
there is no guarantee that planned or ongoing studies will be
completed as planned that future study results will be consistent
with study results to date, that olomorasib will prove to be a safe
and effective treatment for people with certain KRAS
G12C-mutant advanced solid tumors, that olomorasib receive
regulatory approval, or that Lilly will execute its strategy as
expected. For further discussion of these and other risks and
uncertainties that could cause actual results to differ from
Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings
with the United States Securities and Exchange Commission. Except
as required by law, Lilly undertakes no duty to update
forward-looking statements to reflect events after the date of this
release.
1 Canon J. et al. Nature 2019, 575, 217-223
2 Salem M. et al. Ann Oncol 2021, 32 (3 Suppl): S218
3 Peng S-B, Si C, Zhang Y, et al. Abstract 1259:
Preclinical characterization of Ly3537982, a novel, highly
selective and potent KRAS-G12C inhibitor. Cancer
Research. 2021;81(13_Supplement):1259-1259.
doi:10.1158/1538-7445.am2021-1259
Refer
to:
|
Megan Talon;
megan.talon@lilly.com; 463-209-1470 (Media)
|
|
Joe Fletcher;
jfletcher@lilly.com; 317-296-2884 (Investors)
|
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