- 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.
FLORENCE, Italy and NEW
YORK, May 24, 2024 /PRNewswire/ -- 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.
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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