On May 23, 2024 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, reported that it will present updated results from phase 1b/2 ELECTRA and ELEVATE clinical studies evaluating elacestrant (ORSERDU) in combination with other treatments (Press release, Menarini, MAY 23, 2024, View Source;Metastatic-Breast-Cancer-mBC-at-the-ASCO-2024-Annual-Meeting [SID1234643655]). 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) (Free ASCO Whitepaper), 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 (Free ASCO Whitepaper) 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.