INDIANAPOLIS, June 4, 2021 /PRNewswire/ -- Eli Lilly and
Company (NYSE: LLY) today announced new data for the
investigational use of Verzenio® (abemaciclib) in high risk early
breast cancer, and for its oral selective estrogen receptor
degrader (SERD) LY3484356 at the 57th Annual Meeting of
the American Society of Clinical Oncology (ASCO). Lilly is
presenting an exploratory analysis from the positive Phase 3
monarchE trial evaluating Verzenio, a CDK4/6 inhibitor, in a
subgroup of patients with hormone receptor-positive (HR+), human
epidermal growth factor receptor 2-negative (HER2-) high risk early
breast cancer (EBC) who had received neoadjuvant chemotherapy.
Physicians often treat patients with HR+, HER2- breast cancer who
they believe to be at the highest risk of recurrence with
neoadjuvant chemotherapy prior to curative intent surgery. In
addition, Loxo Oncology at Lilly is presenting interim clinical
data from the ongoing Phase 1a trial evaluating the safety and
efficacy of the oral SERD LY3484356 in patients with estrogen
receptor-positive (ER+) advanced breast cancer and endometrial
endometrioid cancer.
New Verzenio Data from monarchE Trial
In an
exploratory analysis of a pre-specified subgroup of patients who
received neoadjuvant chemotherapy (n=2,056), the addition of
Verzenio to endocrine therapy (ET) resulted in a numerically
greater effect size when compared to the intent-to-treat (ITT)
population (n=5,637). This subgroup of patients made up more than
36 percent of the total trial population, had larger tumors at
initial diagnosis and were more commonly premenopausal,
representing one of the highest risk subgroups of patients in
monarchE. Treatment with Verzenio in combination with standard
adjuvant ET decreased the risk of breast cancer recurrence in these
patients by 38.6 percent compared to ET alone (HR: 0.614; 95% CI:
0.473, 0.797). This corresponds to a 6.6 percent difference in the
two-year rate of invasive disease-free survival (IDFS) between arms
(87.2 percent in the Verzenio plus ET arm compared to 80.6 percent
in the ET only control arm). The addition of Verzenio to ET also
reduced the risk of developing metastatic disease by 39 percent
(HR: 0.609; 95% CI: 0.459, 0.809). This corresponds to a 6.7
percent difference in two-year distant relapse-free survival (DRFS)
rates – or time to developing breast cancer that has spread to
other parts of the body – between the arms (89.5 percent in the
Verzenio plus ET arm compared to 82.8 percent in the ET only
control arm). This subgroup analysis was exploratory and not
alpha-controlled for testing statistical significance. Safety data
from the monarchE trial were consistent with the known safety
profile of Verzenio and no new safety signals were observed.
"People who receive neoadjuvant chemotherapy typically represent
a patient population with a substantial risk of breast cancer
recurrence. The data from monarchE further confirm this higher risk
based on the number of events that occurred in the control arm for
this subset of patients," said Maura
Dickler, M.D., distinguished medical fellow, Lilly Oncology.
"Given the need for new treatments for high risk early breast
cancer, especially in this neoadjuvant population, it's encouraging
to see these impressive results with a 38 percent reduction in the
risk of recurrence with the addition of Verzenio to standard
endocrine therapy."
These data build on the results from the Phase 3 monarchE trial,
which met its primary endpoint at the second interim efficacy
analysis by showing a statistically significant improvement in
IDFS. Verzenio, given in combination with ET, decreased the risk of
breast cancer recurrence by 28.7 percent compared to ET alone (HR:
0.713; 95% CI: 0.583, 0.871; p=0.0009) with a 3 percent absolute
difference in the two-year IDFS and DRFS rates in the ITT
population. The monarchE trial is ongoing and patients will
continue to be followed to assess safety, overall survival and
patient reported outcomes, as well as other endpoints.
New Verzenio Phase 3 Trial
Lilly recently initiated a
new Phase 3 trial, eMonarcHER, which will evaluate the safety and
efficacy of Verzenio in combination with standard adjuvant ET in
patients with HR+, HER2+, node-positive, high risk early breast
cancer receiving adjuvant ET after completing surgery and
neoadjuvant and/or adjuvant HER2 targeted therapy. Despite several
advancements for the neoadjuvant and adjuvant treatment of HER2+
breast cancer, research has primarily involved HER2 targeting
agents; however, not all HER2+ breast cancers are successfully
treated with HER2 targeted therapy. This new Phase 3 study
introduces the novel strategy of CDK4/6 inhibition to improve
outcomes with adjuvant hormonal therapy in patients with HR+/HER2+
breast cancer at high risk of recurrence after completion of HER2
targeted therapy. Lilly shared the trial design of eMonarcHER at
ASCO.
Oral SERD (LY3484356) Phase 1a
Data
The first clinical data from the ongoing Phase 1 EMBER
trial of LY3484356 were also presented at ASCO. As of April 7, 2021, 65 patients were enrolled in the
trial, including 58 with ER+ advanced breast cancer and seven with
ER+ endometrial endometrioid cancer (EEC). All patients received
LY3484356 monotherapy. Advanced breast cancer patients had received
a median of two prior lines of therapy with 60 percent receiving
prior fulvestrant, 83 percent a CDK4/6 inhibitor, and 26 percent
chemotherapy. Of 54 patients with available circulating tumor DNA
(ctDNA) data, ESR1 mutations were detected in 37 percent.
Pharmacokinetic analyses during the dose escalation phase
demonstrated dose-proportional increases in LY3484356 exposure
across all evaluated doses (200 mg once daily [QD] to 1200 mg QD).
At all doses, steady state LY3484356 plasma concentrations in
patients exceeded the EC80 range associated with efficacy in
preclinical studies, as well as steady state fulvestrant peak serum
concentration.
No dose limiting toxicities were observed and no maximum
tolerated dose was established. Most treatment-emergent adverse
events were grade 1 or 2 in severity. The treatment-related adverse
events observed most commonly were nausea (19 [29%]), diarrhea (11
[17%]), and fatigue (8 [12%]). Grade 3 treatment-emergent adverse
events occurred in six (9%) patients, which were treatment-related
in two (3%) patients (diarrhea [n=1] and decreased neutrophil count
[n=1]). Serious adverse events occurred in three (5%) patients,
only one of which, grade 3 diarrhea, was treatment-related. No
cardiac safety signal was seen. Dose reductions due to adverse
events occurred in two (3%) patients, one of which was the
treatment-related grade 3 diarrhea. No patient discontinued due to
an adverse event and 400 mg QD has been selected as the recommended
Phase 2 dose.
The efficacy data presented were based on investigator
assessment. Patients were considered efficacy-evaluable for
objective response rate (ORR) if they had RECIST measurable disease
at baseline and at least one post-baseline tumor assessment or
discontinued treatment prior to their first post-baseline
assessment and for clinical benefit rate (CBR) if they were
enrolled at least 24 weeks prior to the data cut-off date. In
advanced breast cancer, two confirmed partial responses were
observed in 35 efficacy-evaluable patients, both occurring after 24
weeks of therapy at the 400 mg dose and in patients who had
received at least three prior regimens for metastatic disease. One
of the observed partial responses was seen in a patient with
fulvestrant, CDK4/6, and chemotherapy-refractory disease. The other
partial response occurred in a patient with three lines of prior
endocrine therapy, including an mTOR inhibitor. The CBR across all
dose levels was 48 percent (13/27). In EEC, no objective responses
were observed among the six efficacy-evaluable patients and the CBR
was 50 percent (2/4). In patients with available serial ctDNA data,
86 percent (18/21) had early (cycle 2 day 1) declines in overall
ctDNA and the degree of decline was generally deeper in patients
who experienced clinical benefit versus those who did not. As of
the data cut-off, 35 patients remained on treatment, including both
patients with partial responses, and 79 percent (31/39) of those
with stable disease or partial responses.
"When we began clinical development of our oral SERD, we hoped
to see pharmacokinetic exposures that exceeded fulvestrant, a
safety profile amenable to chronic use and combination, and
evidence of single agent efficacy. To date, LY3484356 has delivered
on these objectives," said David
Hyman, M.D., chief medical officer, oncology at Lilly. "We
look forward to continuing to explore the profile of LY3484356 in
the ongoing dose expansion portion of the EMBER study and through
the Phase 3 EMBER-3 trial in metastatic ER+, HER2- breast cancer,
set to begin later this year."
Phase 3 EMBER-3 Trial of LY3484356
Lilly is preparing
to initiate a randomized, open-label, Phase 3 study of LY3484356 in
patients with ER+, HER2- locally advanced or metastatic breast
cancer previously treated with endocrine therapy. Patients will be
randomized to receive LY3484356 monotherapy or investigator's
choice of monotherapy endocrine therapy (fulvestrant or
exemestane). The trial, EMBER-3, is expected to begin enrollment in
the third quarter of 2021.
Please refer to Lilly's press release from May 19, 2021 for a full list of
presentations at the meeting.
About the monarchE Trial
monarchE is a Phase 3,
multicenter, randomized, open-label trial that enrolled 5,637
patients with HR+, HER2-, node-positive, high risk early breast
cancer. Patients were randomized 1:1 to Verzenio (150 mg twice
daily) plus standard adjuvant ET or standard adjuvant ET alone.
Patients were treated for two years (treatment period) or until
meeting criteria for discontinuation. Patients in both arms will
receive 5-10 years of ET as clinically indicated (2 years on study
followed by a further 3-8 years in long-term follow-up). The
primary objective is invasive disease-free survival (IDFS) defined
according to the Standard Definitions for Efficacy Endpoints
(STEEP) criteria. In adjuvant breast cancer trials, this includes
the length of time before any cancer comes back, a new cancer
develops or death. Secondary objectives include distant
relapse-free survival, overall survival, safety, pharmacokinetics
and health outcomes.
High risk was specifically defined as women (any menopausal
status) and men with resected HR+, HER2- invasive early breast
cancer with either ≥4 pathologically positive axillary lymph nodes
(ALNs) or 1 to 3 positive ALNs and at least one of the following
high-risk features: primary invasive tumor size ≥5 cm, histological
grade 3 tumor, or central Ki-67 index ≥20%. If applicable, patients
must have also completed adjuvant chemotherapy and radiotherapy
prior to enrolling and have recovered from all acute side
effects.
About Verzenio® (abemaciclib)
Verzenio (abemaciclib)
is an inhibitor of cyclin-dependent kinases (CDK)4/6, which are
activated by binding to D-cyclins. In estrogen receptor-positive
(ER+) breast cancer cell lines, cyclin D1 and CDK4/6 promote
phosphorylation of the retinoblastoma protein (Rb), cell cycle
progression, and cell proliferation.
In vitro, continuous exposure to Verzenio inhibited Rb
phosphorylation and blocked progression from G1 to S phase of the
cell cycle, resulting in senescence and apoptosis (cell death).
Preclinically, Verzenio dosed daily without interruption resulted
in reduction of tumor size. Inhibiting CDK4/6 in healthy cells can
result in side effects, some of which may be serious. Clinical
evidence also suggests that Verzenio crosses the blood-brain
barrier. In patients with advanced cancer, including breast cancer,
concentrations of Verzenio and its active metabolites (M2 and M20)
in cerebrospinal fluid are comparable to unbound plasma
concentrations.
About the EMBER Trial
This global, first-in-human,
open-label Phase 1a/b trial evaluates LY3484356 alone or in
combination with other anticancer therapies in participants with
ER+ advanced breast cancer or endometrioid endometrial cancer. The
trial includes a Phase 1a dose escalation phase and a Phase
1b dose expansion phase. The Phase 1a
dose escalation enrolls patients with ER+/HER2- advanced breast
cancer who have received up to three prior treatment regimens and
ER+ EEC who have progressed after prior platinum-based therapy. The
dose escalation phase followed an i3+3 design with LY3484356
administered orally in 28-day cycles. As dose cohorts were cleared,
additional patient enrollment to cleared dose levels was permitted.
The primary objective of the Phase 1a portion is to determine the
recommended Phase 2 dose. Secondary objectives include assessments
of safety, pharmacokinetics, and anti-tumor activity (objective
response rate (ORR) and clinical benefit rate (CBR), as assessed
per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
About LY3484356
LY3484356 is an investigational, oral
selective estrogen receptor degrader (SERD) with pure antagonistic
properties. The estrogen receptor (ER) is the key therapeutic
target for patients with ER+/HER2- breast cancer. Novel degraders
of ER may overcome endocrine therapy resistance while providing
consistent oral pharmacology and convenience of administration.
LY3484356 was specifically designed to deliver continuous estrogen
receptor target inhibition throughout the dosing period and
regardless of ESR1 mutational status.
LY3484356 is currently being studied in the first-in-human,
multi-center Phase 1a/1b EMBER trial
in patients with estrogen receptor-positive locally advanced or
metastatic breast cancer and other select non-breast cancers and in
the Phase 1 EMBER-2 trial in preoperative, postmenopausal women
with stage I-III, ER+/HER2- breast cancer. For additional
information about LY3484356 clinical trials, please refer to
www.clinicaltrials.gov. Interested patients and physicians can
contact the Loxo Oncology at Lilly clinical trial team by e-mailing
clinicaltrials@loxooncology.com.
INDICATION
Verzenio is indicated for the treatment of
HR+, HER2- advanced or metastatic breast cancer:
- in combination with an aromatase inhibitor for postmenopausal
women as initial endocrine-based therapy
- in combination with fulvestrant for women with disease
progression following endocrine therapy
- as a single agent for adult patients with disease progression
following endocrine therapy and prior chemotherapy in the
metastatic setting
IMPORTANT SAFETY INFORMATION FOR VERZENIO
(abemaciclib)
Diarrhea occurred in 81% of patients receiving Verzenio
plus an aromatase inhibitor in MONARCH 3, 86% of patients receiving
Verzenio plus fulvestrant in MONARCH 2 and 90% of patients
receiving Verzenio alone in MONARCH 1. Grade 3 diarrhea occurred in
9% of patients receiving Verzenio plus an aromatase inhibitor in
MONARCH 3, 13% of patients receiving Verzenio plus fulvestrant in
MONARCH 2 and in 20% of patients receiving Verzenio alone in
MONARCH 1. Episodes of diarrhea have been associated with
dehydration and infection.
Diarrhea incidence was greatest during the first month of
Verzenio dosing. In MONARCH 3, the median time to onset of the
first diarrhea event was 8 days, and the median duration of
diarrhea for Grades 2 and 3 were 11 and 8 days, respectively. In
MONARCH 2, the median time to onset of the first diarrhea event was
6 days, and the median duration of diarrhea for Grades 2 and 3 were
9 days and 6 days, respectively. In MONARCH 3, 19% of patients with
diarrhea required a dose omission and 13% required a dose
reduction. In MONARCH 2, 22% of patients with diarrhea required a
dose omission and 22% required a dose reduction. The time to onset
and resolution for diarrhea were similar across MONARCH 3, MONARCH
2, and MONARCH 1.
Instruct patients that at the first sign of loose stools, they
should start antidiarrheal therapy such as loperamide, increase
oral fluids, and notify their healthcare provider for further
instructions and appropriate follow-up. For Grade 3 or 4 diarrhea,
or diarrhea that requires hospitalization, discontinue Verzenio
until toxicity resolves to ≤Grade 1, and then resume Verzenio at
the next lower dose.
Neutropenia occurred in 41% of patients receiving
Verzenio plus an aromatase inhibitor in MONARCH 3, 46% of patients
receiving Verzenio plus fulvestrant in MONARCH 2 and 37% of
patients receiving Verzenio alone in MONARCH 1. A Grade ≥3 decrease
in neutrophil count (based on laboratory findings) occurred in 22%
of patients receiving Verzenio plus an aromatase inhibitor in
MONARCH 3, 32% of patients receiving Verzenio plus fulvestrant in
MONARCH 2 and in 27% of patients receiving Verzenio alone in
MONARCH 1. In MONARCH 3, the median time to first episode of Grade
≥3 neutropenia was 33 days, and in MONARCH 2 and MONARCH 1, was 29
days. In MONARCH 3, median duration of Grade ≥3 neutropenia was 11
days, and for MONARCH 2 and MONARCH 1 was 15 days.
Monitor complete blood counts prior to the start of Verzenio
therapy, every 2 weeks for the first 2 months, monthly for the next
2 months, and as clinically indicated. Dose interruption, dose
reduction, or delay in starting treatment cycles is recommended for
patients who develop Grade 3 or 4 neutropenia.
Febrile neutropenia has been reported in <1% of patients
exposed to Verzenio in the MONARCH studies. Two deaths due to
neutropenic sepsis were observed in MONARCH 2. Inform patients to
promptly report any episodes of fever to their healthcare
provider.
Severe, life-threatening, or fatal interstitial lung disease
(ILD) and/or pneumonitis can occur in patients treated with
Verzenio and other CDK4/6 inhibitors. Across clinical trials
(MONARCH 1, MONARCH 2, MONARCH 3), 3.3% of Verzenio-treated
patients had ILD/pneumonitis of any grade, 0.6% had Grade 3 or 4,
and 0.4% had fatal outcomes. Additional cases of ILD/pneumonitis
have been observed in the post-marketing setting, with fatalities
reported.
Monitor patients for pulmonary symptoms indicative of
ILD/pneumonitis. Symptoms may include hypoxia, cough, dyspnea, or
interstitial infiltrates on radiologic exams. Infectious,
neoplastic, and other causes for such symptoms should be excluded
by means of appropriate investigations.
Dose interruption or dose reduction is recommended in patients
who develop persistent or recurrent Grade 2 ILD/pneumonitis.
Permanently discontinue Verzenio in all patients with grade 3 or 4
ILD/pneumonitis.
Grade ≥3 increases in alanine aminotransferase (ALT) (6%
versus 2%) and aspartate aminotransferase (AST) (3% versus
1%) were reported in the Verzenio and placebo arms, respectively,
in MONARCH 3. Grade ≥3 increases in ALT (4% versus 2%) and AST (2%
versus 3%) were reported in the Verzenio and placebo arms
respectively, in MONARCH 2.
In MONARCH 3, for patients receiving Verzenio plus an aromatase
inhibitor with Grade ≥3 increases in ALT or AST, median time to
onset was 61 and 71 days, respectively, and median time to
resolution to Grade <3 was 14 and 15 days, respectively. In
MONARCH 2, for patients receiving Verzenio plus fulvestrant with
Grade ≥3 increases in ALT or AST, median time to onset was 57 and
185 days, respectively, and median time to resolution to Grade
<3 was 14 and 13 days, respectively.
For assessment of potential hepatotoxicity, monitor liver
function tests (LFTs) prior to the start of Verzenio therapy, every
2 weeks for the first 2 months, monthly for the next 2 months, and
as clinically indicated. Dose interruption, dose reduction, dose
discontinuation, or delay in starting treatment cycles is
recommended for patients who develop persistent or recurrent Grade
2, or Grade 3 or 4, hepatic transaminase elevation.
Venous thromboembolic events were reported in 5% of
patients treated with Verzenio plus an aromatase inhibitor as
compared to 0.6% of patients treated with an aromatase inhibitor
plus placebo in MONARCH 3. Venous thromboembolic events were
reported in 5% of patients treated with Verzenio plus fulvestrant
in MONARCH 2 as compared to 0.9% of patients treated with
fulvestrant plus placebo. Venous thromboembolic events included
deep vein thrombosis, pulmonary embolism, pelvic venous thrombosis,
cerebral venous sinus thrombosis, subclavian and axillary vein
thrombosis, and inferior vena cava thrombosis. Across the clinical
development program, deaths due to venous thromboembolism have been
reported. Monitor patients for signs and symptoms of venous
thrombosis and pulmonary embolism and treat as medically
appropriate.
Verzenio can cause fetal harm when administered to a
pregnant woman based on findings from animal studies and the
mechanism of action. In animal reproduction studies, administration
of abemaciclib to pregnant rats during the period of organogenesis
caused teratogenicity and decreased fetal weight at maternal
exposures that were similar to the human clinical exposure based on
area under the curve (AUC) at the maximum recommended human dose.
Advise pregnant women of the potential risk to a fetus. Advise
females of reproductive potential to use effective contraception
during treatment with Verzenio and for at least 3 weeks after the
last dose. There are no data on the presence of Verzenio in human
milk or its effects on the breastfed child or on milk production.
Advise lactating women not to breastfeed during Verzenio treatment
and for at least 3 weeks after the last dose because of the
potential for serious adverse reactions in breastfed infants. Based
on findings in animals, Verzenio may impair fertility in males of
reproductive potential.
The most common adverse reactions (all grades, ≥10%)
observed in MONARCH 3 for Verzenio plus anastrozole or
letrozole and ≥2% higher than placebo plus anastrozole or
letrozole vs placebo plus anastrozole or letrozole were
diarrhea (81% vs 30%), neutropenia (41% vs 2%), fatigue (40% vs
32%), infections (39% vs 29%), nausea (39% vs 20%), abdominal pain
(29% vs 12%), vomiting (28% vs 12%), anemia (28% vs 5%), alopecia
(27% vs 11%), decreased appetite (24% vs 9%), leukopenia (21% vs
2%), creatinine increased (19% vs 4%), constipation (16% vs 12%),
ALT increased (16% vs 7%), AST increased (15% vs 7%), rash (14% vs
5%), pruritus (13% vs 9%), cough (13% vs 9%), dyspnea (12% vs 6%),
dizziness (11% vs 9%), weight decreased (10% vs 3%), influenza-like
illness (10% vs 8%), and thrombocytopenia (10% vs 2%).
The most common adverse reactions (all grades, ≥10%)
observed in MONARCH 2 for Verzenio plus fulvestrant and ≥2%
higher than placebo plus fulvestrant vs placebo plus
fulvestrant were diarrhea (86% vs 25%), neutropenia (46% vs
4%), fatigue (46% vs 32%), nausea (45% vs 23%), infections (43% vs
25%), abdominal pain (35% vs 16%), anemia (29% vs 4%), leukopenia
(28% vs 2%), decreased appetite (27% vs 12%), vomiting (26% vs
10%), headache (20% vs 15%), dysgeusia (18% vs 3%),
thrombocytopenia (16% vs 3%), alopecia (16% vs 2%), stomatitis (15%
vs 10%), ALT increased (13% vs 5%), pruritus (13% vs 6%), cough
(13% vs 11%), dizziness (12% vs 6%), AST increased (12% vs 7%),
peripheral edema (12% vs 7%), creatinine increased (12% vs <1%),
rash (11% vs 4%), pyrexia (11% vs 6%), and weight decreased (10% vs
2%).
The most common adverse reactions (all grades, ≥10%)
observed in MONARCH 1 with Verzenio were diarrhea (90%),
fatigue (65%), nausea (64%), decreased appetite (45%), abdominal
pain (39%), neutropenia (37%), vomiting (35%), infections (31%),
anemia (25%), thrombocytopenia (20%), headache (20%), cough (19%),
leukopenia (17%), constipation (17%), arthralgia (15%), dry mouth
(14%), weight decreased (14%), stomatitis (14%), creatinine
increased (13%), alopecia (12%), dysgeusia (12%), pyrexia (11%),
dizziness (11%), and dehydration (10%).
The most frequently reported ≥5% Grade 3 or 4 adverse
reactions that occurred in the Verzenio arm vs the placebo arm
of MONARCH 3 were neutropenia (22% vs 2%), diarrhea (9% vs
1%), leukopenia (8% vs <1%), ALT increased (7% vs 2%), and
anemia (6% vs 1%).
The most frequently reported ≥5% Grade 3 or 4 adverse
reactions that occurred in the Verzenio arm vs the placebo arm
of MONARCH 2 were neutropenia (27% vs 2%), diarrhea (13% vs
<1%), leukopenia (9% vs 0%), anemia (7% vs 1%), and infections
(6% vs 3%).
The most frequently reported ≥5% Grade 3 or 4 adverse
reactions from MONARCH 1 with Verzenio were neutropenia
(24%), diarrhea (20%), fatigue (13%), infections (7%), leukopenia
(6%), anemia (5%), and nausea (5%).
Lab abnormalities (all grades; Grade 3 or 4) for
MONARCH 3 in ≥10% for Verzenio plus anastrozole or letrozole and
≥2% higher than placebo plus anastrozole or letrozole vs placebo
plus anastrozole or letrozole were increased serum creatinine
(98% vs 84%; 2% vs 0%), decreased white blood cells (82% vs 27%;
13% vs <1%), anemia (82% vs 28%; 2% vs 0%), decreased neutrophil
count (80% vs 21%; 22% vs 3%), decreased lymphocyte count (53% vs
26%; 8% vs 2%), decreased platelet count (36% vs 12%; 2% vs
<1%), increased ALT (48% vs 25%; 7% vs 2%), and increased AST
(37% vs 23%; 4% vs <1%).
Lab abnormalities (all grades; Grade 3 or 4) for
MONARCH 2 in ≥10% for Verzenio plus fulvestrant and ≥2% higher
than placebo plus fulvestrant vs placebo plus fulvestrant were
increased serum creatinine (98% vs 74%; 1% vs 0%), decreased white
blood cells (90% vs 33%; 23% vs 1%), decreased neutrophil count
(87% vs 30%; 33% vs 4%), anemia (84% vs 33%; 3% vs <1%),
decreased lymphocyte count (63% vs 32%; 12% vs 2%), decreased
platelet count (53% vs 15%; 2% vs 0%), increased ALT (41% vs 32%;
5% vs 1%), and increased AST (37% vs 25%; 4% vs 4%).
Lab abnormalities (all grades; Grade 3 or 4) for MONARCH
1 were increased serum creatinine (98%; <1%), decreased
white blood cells (91%; 28%), decreased neutrophil count (88%;
27%), anemia (68%; 0%), decreased lymphocyte count (42%; 14%),
decreased platelet count (41%; 2%), increased ALT (31%; 3%), and
increased AST (30%; 4%).
Strong and moderate CYP3A inhibitors increased the
exposure of abemaciclib plus its active metabolites to a clinically
meaningful extent and may lead to increased toxicity. Avoid
concomitant use of the strong CYP3A inhibitor ketoconazole.
Ketoconazole is predicted to increase the AUC of abemaciclib by up
to 16-fold. In patients with recommended starting doses of 200 mg
twice daily or 150 mg twice daily, reduce the Verzenio dose to 100
mg twice daily with concomitant use of strong CYP3A inhibitors
other than ketoconazole. In patients who have had a dose reduction
to 100 mg twice daily due to adverse reactions, further reduce the
Verzenio dose to 50 mg twice daily with concomitant use of strong
CYP3A inhibitors. If a patient taking Verzenio discontinues a
strong CYP3A inhibitor, increase the Verzenio dose (after 3 to 5
half-lives of the inhibitor) to the dose that was used before
starting the inhibitor. With concomitant use of moderate CYP3A
inhibitors, monitor for adverse reactions and consider reducing the
Verzenio dose in 50 mg decrements. Patients should avoid grapefruit
products.
Avoid concomitant use of strong or moderate CYP3A inducers
and consider alternative agents. Coadministration of strong or
moderate CYP3A inducers decreased the plasma concentrations of
abemaciclib plus its active metabolites and may lead to reduced
activity.
With severe hepatic impairment (Child-Pugh Class C),
reduce the Verzenio dosing frequency to once daily. The
pharmacokinetics of Verzenio in patients with severe renal
impairment (CLcr <30 mL/min), end stage renal disease, or in
patients on dialysis is unknown. No dosage adjustments are
necessary in patients with mild or moderate hepatic (Child-Pugh A
or B) and/or renal impairment (CLcr ≥30-89 mL/min).
AL HCP ISI 17SEP2019
Please see full Prescribing
Information for Verzenio.
About Lilly Oncology
For more than 50 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 LillyOncology.com.
About Loxo Oncology at Lilly
Loxo Oncology at Lilly was created in December 2019, combining
the Lilly Research Laboratories oncology organization
and Loxo Oncology, which was acquired by Lilly in early
2019. Loxo Oncology at Lilly brings together the focus and
spirit of a biotech with the scale and resources of large pharma,
with the goal of rapidly delivering impactful new medicines for
people with cancer. Our approach centers on creating new oncology
medicines that unequivocally work early in clinical development and
will matter to patients.
About Eli Lilly and Company
Lilly is a global health care leader that unites caring with
discovery to create medicines that 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 lilly.com and lilly.com/newsroom. P-LLY
© Lilly USA, LLC 2021. ALL RIGHTS RESERVED.
Verzenio® is a trademark owned by or licensed to
Eli Lilly and Company, its subsidiaries, or affiliates.
Lilly Forward-Looking Statement
This press release
contains forward-looking statements (as that term is defined in the
Private Securities Litigation Reform Act of 1995) about Lilly's
oncology portfolio and pipeline, including Verzenio (abemaciclib)
and LY3484356 as treatments for patients with breast
cancer and reflects Lilly's current beliefs and expectations.
However, as with any pharmaceutical product, there are substantial
risks and uncertainties in the process of research, development,
regulatory approval, and commercialization. Among other things,
there can be no guarantee that future studies will be completed as
planned, that future study results will be consistent with the
results to date, or that Verzenio or LY3484356 will receive
(or receive additional) regulatory approvals or be commercially
successful. For further discussion of these and other risks and
uncertainties, see Lilly's most recent 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.
Refer to:
|
Courtney Kasinger,
ckasinger@lilly.com; 317-501-7056 (Lilly): media
|
|
Lauren Cohen;
lcohen@loxooncology.com; 617-678-2067 (Loxo Oncology at Lilly):
media
|
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Kevin Hern,
hern_kevin_r@lilly.com; 317-277-1838 (Lilly): investors
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multimedia:http://www.prnewswire.com/news-releases/lilly-announces-new-clinical-data-from-verzenio-and-oral-serd-programs-at-the-american-society-of-clinical-oncology-annual-meeting-301305702.html
SOURCE Eli Lilly and Company