- The ELECTRA and ELEVATE studies were designed to overcome
different resistance mechanisms and improve patient outcomes with
oral-oral combination options.
- Updated results from the ELECTRA study, evaluating elacestrant
in combination with abemaciclib regardless of metastatic site, show
a safety profile consistent with previous results. Recommended
phase 2 dose for this combination is presented.
- Updated analysis from the ELEVATE study demonstrates that all
evaluable elacestrant plus targeted therapy combination arms are
consistent with the known safety profiles of everolimus, alpelisib,
ribociclib and palbociclib plus standard of care endocrine therapy.
Recommended phase 2 dose for the combination of elacestrant and
everolimus is presented.
The Menarini Group (“Menarini”), a leading international
pharmaceutical and diagnostics company, and Stemline Therapeutics,
Inc. (“Stemline”), a wholly-owned subsidiary of the Menarini Group,
focused on bringing transformational oncology treatments to cancer
patients, will present updated results from phase 1b/2 ELECTRA and
ELEVATE clinical studies evaluating elacestrant (ORSERDU®) in
combination with other treatments. Both the ELECTRA and ELEVATE
studies were designed to overcome different resistance mechanisms
observed in estrogen receptor-positive (ER+), HER2-negative (HER2-)
metastatic breast cancer (mBC) and improve patient outcomes through
novel oral-oral combination treatment options. Data will be
presented at the 2024 American Society of Clinical Oncology (ASCO),
on June 2 from 9 a.m. to 12 p.m. CT.
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The ELECTRA study is evaluating elacestrant in combination with
abemaciclib in patients with ER+, HER2- metastatic breast cancer
with brain metastases; however, the phase 1b portion of this study
was conducted in all metastatic sites, including brain metastases.
The updated phase 1b results continue to show a satisfactory safety
profile, consistent with prior findings, and promising activity in
patients with ER+, HER2- advanced or mBC regardless of metastatic
site. Based on the results of this portion of the study, the
recommended phase 2 dose (RP2D) will be reported as part of the
data presentation. Currently, the phase 2 portion of ELECTRA is
ongoing at the RP2D to further characterize the efficacy and safety
in patients with ER+, HER2- metastatic breast cancer with brain
metastases, since both elacestrant and abemaciclib cross the
blood-brain barrier.
“It is encouraging to see that, even in the early stages of the
trial, the combination of elacestrant plus abemaciclib indicates a
tolerable and manageable safety profile for the patients in the
clinical trial,” said Erika Hamilton, MD, Director of Breast Cancer
Research and Executive Chair of the Breast Cancer Research
Executive Committee for Sarah Cannon Research Institute. “The study
continues to demonstrate elacestrant’s potential in combination
with other therapies and we look forward to analyzing more data
from this combination for this patient population in need of new
options.”
The ELEVATE study is evaluating elacestrant in combination with
CDK4/6 inhibitors (palbociclib, abemaciclib and ribociclib) and
with inhibitors of the PI3K/AKT/mTOR pathway (everolimus, alpelisib
and capivasertib). The updated Phase 1b results show that the
combinations evaluated are consistent with the known safety
profiles of each targeted therapy plus standard of care endocrine
therapy. Based on the results of this portion of the study, the
RP2D will be reported for elacestrant in combination with
everolimus. Additional cohorts, including elacestrant plus
capivasertib, are currently under evaluation to further
characterize the safety, assess efficacy and determine the RP2D for
each combination arm. Phase 2 for the combination of elacestrant
and abemaciclib in ER+, HER2- metastatic breast cancer,
irrespective of the metastatic site, is already ongoing.
“As we evaluate the various combinations of elacestrant plus
CDK4/6 and PI3K/AKT/mTOR inhibitors, we continue to see consistent
and manageable safety findings across all arms of the trial, and so
far, elacestrant does not appear to add any incremental toxicity to
the combination regimens in which it is being studied,” Hope S.
Rugo, MD, Professor of Medicine and Winterhof Family Endowed
Professor in Breast Cancer, Director, Breast Oncology and Clinical
Trials Education, University of California San Francisco. “These
data build on our understanding of elacestrant’s role in metastatic
breast cancer and reinforce its potential as an endocrine therapy
backbone in combination regimens.”
“Since its approval in 2023, ORSERDU has had a meaningful impact
as an endocrine therapy for people who are living with ER+, HER2-
metastatic breast cancer harboring ESR1 mutations,” said Elcin
Barker Ergun, CEO of the Menarini Group. “The data we are
presenting at ASCO highlight elacestrant’s potential to further
enhance patient outcomes when combined with other compounds.”
About The Elacestrant Clinical Development Program
Elacestrant is also being investigated in several
company-sponsored clinical trials in metastatic breast cancer
disease, alone or in combination with other therapies. ELEVATE
(NCT05563220) is a phase 1b/2 clinical trial evaluating the safety
and efficacy of elacestrant combined with alpelisib, everolimus,
capivasertib, palbociclib, ribociclib or abemaciclib. ELECTRA
(NCT05386108) is an open-label phase 1b/2, multicenter study
evaluating elacestrant in combination with abemaciclib in patients
with ER+, HER2- breast cancer. The phase 2 portion evaluates this
treatment regimen in patients with brain metastases. ELCIN
(NCT05596409) is a phase 2 trial evaluating the efficacy of
elacestrant in patients with ER+, HER2- advanced/metastatic breast
cancer who received one or two prior hormonal therapies and no
prior CDK4/6 inhibitors in the metastatic setting. ADELA
(NCT06382948) is a phase 3 randomized, double-blinded trial
evaluating elacestrant in combination with everolimus in patients
with ER+, HER2- mBC with ESR1-mut tumors. Elacestrant is also being
evaluated in additional investigator-led trials, in trials
conducted in collaboration with other companies, in metastatic
breast cancer as well as in early disease.
About ORSERDU (elacestrant)
U.S. Indication: ORSERDU (elacestrant), 345 mg tablets,
is indicated for the treatment of postmenopausal women or adult men
with estrogen receptor (ER)-positive, human epidermal growth factor
receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic
breast cancer with disease progression following at least one line
of endocrine therapy.
Full prescribing information for the U.S. can be found at
www.orserdu.com.
Important Safety Information
Warning and Precautions
Dyslipidemia: Hypercholesterolemia and
hypertriglyceridemia occurred in patients taking ORSERDU at an
incidence of 30% and 27%, respectively. The incidence of Grade 3
and 4 hypercholesterolemia and hypertriglyceridemia were 0.9% and
2.2%, respectively. Monitor lipid profile prior to starting and
periodically while taking ORSERDU.
Embryo-Fetal Toxicity: Based on findings in
animals and its mechanism of action, ORSERDU can cause fetal harm
when administered to a pregnant woman. Advise pregnant women and
females of reproductive potential of the potential risk to a fetus.
Advise females of reproductive potential to use effective
contraception during treatment with ORSERDU and for 1 week after
the last dose. Advise male patients with female partners of
reproductive potential to use effective contraception during
treatment with ORSERDU and for 1 week after the final dose.
Adverse Reactions
Serious adverse reactions occurred in 12% of
patients who received ORSERDU. Serious adverse reactions in >1%
of patients who received ORSERDU were musculoskeletal pain (1.7%)
and nausea (1.3%). Fatal adverse reactions occurred in 1.7% of
patients who received ORSERDU, including cardiac arrest, septic
shock, diverticulitis, and unknown cause (one patient each).
The most common adverse reactions
(>10%), including laboratory
abnormalities, of ORSERDU were musculoskeletal pain (41%), nausea
(35%), increased cholesterol (30%), increased AST (29%), increased
triglycerides (27%), fatigue (26%), decreased hemoglobin (26%),
vomiting (19%), increased ALT (17%), decreased sodium (16%),
increased creatinine (16%), decreased appetite(15%), diarrhea(13%),
headache (12%), constipation (12%), abdominal pain (11%), hot flush
(11%), and dyspepsia (10%).
Drug interactions
Concomitant use with CYP3A4 Inducers and/or
inhibitors: Avoid concomitant use of strong or moderate CYP3A4
inhibitors with ORSERDU. Avoid concomitant use of strong or
moderate CYP3A4 inducers with ORSERDU.
Use in specific populations
Lactation: Advise lactating women to not
breastfeed during treatment with ORSERDU and for 1 week after the
last dose.
Hepatic Impairment: Avoid use of ORSERDU in
patients with severe hepatic impairment (Child-Pugh C). Reduce the
dose of ORSERDU in patients with moderate hepatic impairment
(Child-Pugh B).
The safety and effectiveness of ORSERDU in
pediatric patients have not been established.
To report SUSPECTED ADVERSE REACTIONS, contact Stemline
Therapeutics, Inc. at 1-877-332-7961 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
About The Menarini Group
The Menarini Group is a leading international pharmaceutical and
diagnostics company, with a turnover of $4.7 billion and over
17,000 employees. Menarini is focused on therapeutic areas with
high unmet needs with products for cardiology, oncology,
pneumology, gastroenterology, infectious diseases, diabetology,
inflammation, and analgesia. With 18 production sites and 9
Research and Development centers, Menarini’s products are available
in 140 countries worldwide. For further information, please visit
www.menarini.com.
About Stemline Therapeutics Inc.
Stemline Therapeutics, Inc. (“Stemline”) a wholly-owned
subsidiary of the Menarini Group, is a commercial-stage
biopharmaceutical company focused on the development and
commercialization of novel oncology therapeutics. Stemline
commercializes ORSERDU® (elacestrant) in the U.S. and Europe, an
oral endocrine therapy indicated for the treatment of
postmenopausal women or adult men with estrogen receptor
(ER)-positive, human epidermal growth factor receptor 2
(HER2)-negative, ESR1-mutated advanced or metastatic breast cancer
with disease progression following at least one line of endocrine
therapy. Stemline also commercializes ELZONRIS® (tagraxofusp-erzs),
a novel targeted treatment directed to CD123 for patients with
blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive
hematologic cancer, in the United States and Europe, which is the
only approved treatment for BPDCN in the U.S. and E.U. to date.
Stemline also commercializes NEXPOVIO® (selinexor) in Europe, an
XPO1 inhibitor for multiple myeloma. Stemline also has an extensive
clinical pipeline of small molecules and biologics in various
stages of development for a host of solid and hematologic
cancers.
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Media
The Menarini Group Valeria Speroni Cardi Email:
pressoffice@menarini.com
Stemline Therapeutics, Inc. Cheya Pope Email:
media@menarinistemline.com