ERADICATE: A Phase Ib/II Study of Elacestrant Plus Trastuzumab Deruxtecan in Patients With CDK4/6 Inhibitor and Endocrine-resistant HR+/HER2-low or HER2-ultralow Metastatic Breast Cancer

The goal of this study is to evaluate the safety and efficacy of elacestrant in combination with trastuzumab deruxtecan (T-DXd) in participants with hormone receptor-positive (HR+), HER2-low or HER2-ultralow, metastatic breast cancer that is resistant to prior CDK4/6 inhibitor and endocrine therapy.
The names of the study drugs involved in this study are:
* Elacestrant (a type of selective estrogen receptor degrader)
* Trastuzumab deruxtecan (a type of standard of care antibody drug conjugate)

Start Date01 Mar 2026

Sponsor / Collaborator

Dana-Farber Cancer Institute, Inc.

[+1]

NCT07242352

/ Not yet recruitingPhase 3IIT

Dynamic Marker - Adjusted Therapy Comparing Adjuvant Elacestrant With Standard Endocrine Treatment in Genomically and/or Clinically High-risk ER+/HER2- Early Breast Cancer (ADAPTela)

In this clinical trial, the Sponsor plans to investigate whether patients with HR+/HER2- eBC identified during routine clinical assessments and treatments as having intermediate to high-risk (based on Oncotype DX® or similar tests and on response assessment to 2-6 weeks of preoperative ET) achieve a survival benefit from an initial 5-years use of elacestrant (with or without a CDK 4/6 inhibitor) followed by SoC ET for further 0-2.5 years in comparison to at least 5 up to 7.5 years SoC ET therapy (+/- CDK4/6 inhibitor).
Based on several studies in the metastatic setting, it is reasonable to assume that the adjuvant use of elacestrant with or without CDK 4/6 inhibitors will prevent or delay the activation of mechanisms conferring resistance to ET (e.g., ESR1 mutations).

Start Date31 Jan 2026

Sponsor / Collaborator

Berlin-Chemie/Menarini Pharma GmbH

NCT07222215

/ RecruitingPhase 2IIT

A Phase II Multi-Center Open-label Randomized Study of CAPecitabine in Combination With ELAcestrant Versus Capecitabine Alone in Advanced Estrogen Receptor-Positive Breast Cancer (CAPELA)

The goal of this research study is to compare a combination of two drugs, capecitabine and elacestrant to capecitabine alone as a treatment for advanced estrogen receptor-positive (ER+) breast cancer. This study is designed for participants with cancer that has previously stopped responding to medication in the class of therapy called CDK 4/6 inhibitors, including palbociclib, ribociclib, or abemaciclb.
The names of the study drugs involved in this study are:
* Elacestrant (a type of selective estrogen receptor degrader)
* Capecitabine (a type of fluoropyrimidine antimetabolite)

Start Date01 Jan 2026

Sponsor / Collaborator

Dana-Farber Cancer Institute, Inc.

[+3]

100 Clinical Results associated with Elacestrant hydrochloride

100 Translational Medicine associated with Elacestrant hydrochloride

100 Patents (Medical) associated with Elacestrant hydrochloride

104

Literatures (Medical) associated with Elacestrant hydrochloride

06 Jan 2026·CLINICAL CANCER RESEARCH

Real-World Outcomes of Elacestrant in ER+, HER2−, ESR1 -Mutant Metastatic Breast Cancer

Article

Author: Wasserman, Tomer ; Lustberg, Maryam ; Gradishar, William ; Kloss, Sebastian ; Pegram, Mark ; Wander, Seth A. ; Rugo, Hope S. ; Swallow, Elyse ; McArthur, Heather ; Tolaney, Sara M. ; Kaklamani, Virginia ; Mahtani, Reshma ; Maitland, Jessica

Abstract:

Purpose::

The EMERALD trial led to the approval of elacestrant for estrogen receptor (ER)–positive, HER2-negative, estrogen receptor 1 (ESR1)–mutated advanced or metastatic breast cancer (mBC) with disease progression following at least one line of endocrine therapy (ET). Subgroup analyses provided evidence suggesting that elacestrant enables ET sequencing in the second line before other targeted combinations, which could delay chemotherapy-based regimens.

Experimental Design::

This study used claims data from the Komodo Research Dataset linked with Foundation Medicine Inc. clinical genomic data from patients with estrogen receptor+/HER2− mBC harboring an ESR1 mutation treated with elacestrant. The primary outcome measure was time to next treatment (TTNT).

Results::

Among 306 patients, 93.8% had prior ET ± cyclin-dependent kinase 4/6 inhibitor for ≥12 months, 50.0% had prior chemotherapy, and 72.2% had prior fulvestrant. Median TTNT (mTTNT) was 8.2 months [95% confidence interval (CI), 6.3–13.0] in patients with 1 to 2 prior lines and 7.5 months (95% CI, 7.1–9.9) in those with ≥3 prior lines of ET. In patients with coexisting ESR1- and PI3K-pathway–mutated tumors, mTTNT was 6.3 months (95% CI, 4.8–7.9). mTTNT was 7.9 months (95% CI, 7.1–9.8) in all patients and was also sustained in patients with no prior fulvestrant [12.9 months (95% CI, 7.2–not reached)], no prior chemotherapy [8.4 months (95% CI, 7.1–13.3)], visceral metastasis [7.9 months (95% CI, 7.0–9.9)], and liver metastases [7.2 months (95% CI, 6.3–9.0)].

Conclusions::

Elacestrant demonstrated a durable benefit in real-world clinical practice, particularly in earlier lines and in patients with prolonged prior ET exposure. Despite coexisting ESR1 and PI3K pathway mutations, TTNT remained clinically meaningful, reinforcing the role of elacestrant in personalized ET sequencing strategies prior to chemotherapy, antibody–drug conjugates, or targeted combinations.See related article by Lloyd et al., p. 169

06 Jan 2026·CLINICAL CANCER RESEARCH

Clinical and Genomic Factors Associated with Elacestrant Outcomes in ESR1- Mutant Metastatic Breast Cancer

Article

Author: Weipert, Caroline M. ; Lloyd, Maxwell R. ; Wander, Seth A. ; Zhang, Nicole ; Brufsky, Adam M. ; Bardia, Aditya ; Hamilton, Erika P. ; Kalinsky, Kevin ; Ali, Azka ; Solomon, Sheila R. ; Lipsyc-Sharf, Marla D. ; Saha, Jayati

Abstract:

Purpose::

ESR1 mutations mediate resistance to antiestrogen therapy in hormone receptor–positive metastatic breast cancer (MBC). Elacestrant, an oral selective estrogen receptor degrader, improves progression-free survival over standard endocrine therapy in ESR1-mutant MBC. We assessed real-world elacestrant use and clinical–genomic factors associated with outcomes.

Experimental Design::

This study used the GuardantINFORM database, linking >42,000 real-world breast cancer cases with sequencing and claims data. We included patients with activating ESR1 mutations detected <6 months before elacestrant initiation (January 2023–March 2024). Outcomes of time-to-treatment-discontinuation, time-to-next-treatment (TTNT), and overall survival were estimated with Kaplan–Meier and Cox regression analysis, adjusting for clinical variables.

Results::

We identified 756 patients (76% with prior cyclin-dependent kinase-4/6 inhibitor and 38% with prior chemotherapy exposure), and 742 (98.2%) were evaluable for outcomes. The median TTNT was 6.4 months, and the time-to-treatment-discontinuation was 4.6 months. In those with ≤1 prior lines of metastatic therapy, the TTNT was 8.8 months, compared with 6.0 months in the third-line setting. Prior fulvestrant exposure trended toward shorter treatment duration (hazard ratio, 1.19; 95% confidence interval, 0.91–1.56). Higher ESR1 polyclonality (≥4 alterations; 11% of patients) correlated with a shorter TTNT of 5.2 months (hazard ratio, 1.44; 95% confidence interval, 1.01–2.06), but efficacy was consistent across ESR1 alleles (e.g., Y537S and D538G). Disease with dual ESR1 and PI3K pathway mutations (PIK3CA, AKT1, and PTEN) had a median TTNT of 5.2 months.

Conclusions::

In ESR1-mutant MBC, elacestrant treatment durations support the routine use of elacestrant monotherapy in appropriately selected patients. For patients with concurrent ESR1 and PI3K pathway mutations, single-agent activity was comparable with outcomes observed in phase III studies.See related article by Rugo et al., p. 179

01 Nov 2025·EClinicalMedicine

Efficacy and safety of systemic therapies following progression on CDK4/6 inhibitors in patients with HR+/HER2− metastatic breast cancer: a systematic review and network meta-analysis

Article

Author: Chiodini, Paolo ; De Angelis, Carmine ; Dieci, Maria Vittoria ; Pagliuca, Martina ; Botticelli, Andrea ; Cataldo, Maria Letizia ; De Laurentiis, Michelino ; Giordano, Antonio ; Fordellone, Mario ; Criscitiello, Carmen ; Vernieri, Claudio ; Mangiacotti, Federica ; Caputo, Roberta ; Malorni, Luca ; Caltavituro, Aldo ; Grieco, Angela ; Longobardi, Alessandra ; Giuliano, Mario ; Gerratana, Lorenzo ; Buonaiuto, Roberto ; Arpino, Grazia ; Lambertini, Matteo

Background:

In the absence of head-to-head trials, optimal treatment sequencing following disease progression on a CDK4/6 inhibitor (CDK4/6i) combined with endocrine therapy (ET) in hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (mBC) remains challenging. To address this gap, we conducted a systematic review and network meta-analysis (NMA) to provide evidence-based guidance for treatment selection in this setting.

Methods:

We identified randomized phase II-III trials involving HR+/HER2- mBC patients whose tumors progressed on CDK4/6i-based therapy, published between January 1, 2014 and June 6, 2025 (PROSPERO n° CRD42024604417). Hazard ratios (HRs) for progression-free survival (PFS) were extracted from published data and analyzed using a frequentist random-effects model. Subgroup analyses were performed based on the duration of CDK4/6i treatment and the presence of ESR1 or PI3K/PTEN/AKT pathway alterations. Treatments were compared with conventional ET or chemotherapy and ranked using the P-score metric. Confidence in network estimates was evaluated using the CINeMA framework. Safety data, including grade ≥3 adverse events (AEs) and treatment discontinuation, were descriptively analyzed.

Findings:

Twenty-eight randomized trials (n = 6544) were included in the NMA. Sapanisertib plus fulvestrant provided the greatest PFS benefit (HR 0.34, 95% CI 0.14-0.82) but had a high discontinuation rate (>15%). Among the approved therapies, ribociclib plus ET (HR 0.57, 95% CI 0.39-0.84), capivasertib plus fulvestrant (HR 0.62, 95% CI 0.51-0.75), and elacestrant (HR 0.70, 95% CI 0.55-0.89) demonstrated superior efficacy. Elacestrant was most effective in patients with ESR1-mutant tumors and among patients with prolonged prior CDK4/6i exposure. Ipatasertib and alpelisib showed the greatest benefits in patients with PI3K/PTEN/AKT alterations. Antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan and sacituzumab govitecan, outperformed standard chemotherapy, albeit with higher toxicity.

Interpretation:

Combinations of targeted agents with ET or novel endocrine agents such as oral selective estrogen receptor degraders (SERDs) demonstrated favorable efficacy and safety profiles in biomarker-selected populations, supporting a shift toward biomarker-driven treatment algorithms. In endocrine-resistant diseases that require chemotherapy, ADCs are the most effective therapeutic option.

Funding:

We acknowledge financial support under the National Recovery and Resilience Plan (NRRP), Mission 4, Component 2, Investment 1.1, Call for tender No. 1409 published on 14.9.2022 by the Italian Ministry of University and Research (MUR), funded by the European Union - NextGenerationEU - Project Title: Identifying predictive/prognostic biomarkers and mechanisms underlying resistance to CDK4/6 inhibition beyond progression in hormone receptor-positive/HER2-negative metastatic breast cancer - CUP E53D23020460001 (Project code: P2022FK2J8, ERC panel: LS7, Principal Investigator: Carmine De Angelis). Grant Assignment Decree No. 1369 adopted on 01.09.2023 by the Italian Ministry of University and Research (MUR).

134

News (Medical) associated with Elacestrant hydrochloride

12 Dec 2025

·www.fiercepharma.com

Lilly shifts ambition for broader oral SERD label to largest oncology trial in company history

With target enrollment of 8,000 patients, the Ember-4 trial of Inluriyo in early-stage breast cancer will be Eli Lilly’s largest oncology trial in the company’s history, according to Jake Van Naarden, president of Lilly Oncology. Eli Lilly will not seek a broad FDA approval for a combination of the company’s oral SERD med Inluriyo and CDK4/6 inhibitor Verzenio despite seemingly promising phase 3 results.Instead, the Indianapolis pharma will only pursue a label for the combo covering patients with ER-positive, HER2-negative advanced breast cancer who carry ESR1 gene mutations, the same limited indication that Inluriyo monotherapy recently obtained from the FDA, Jake Van Naarden, president of Lilly Oncology, told Fierce Pharma.“I don’t think there’s a path to an [intent-to-treat] indication. It’s just not been where the conversation has been,” Van Naarden said in an interview with Fierce about Lilly’s interactions with the FDA, later adding that “we’re not going to fight with them on that.” The intent-to-treat description refers to all participants randomized in a clinical trial, rather than specific subgroups. The revelation comes as a disappointment, because, while Inluriyo itself previously failed to show a progression-free survival benefit against endocrine therapy in patients without ESR1 mutations in the company’s phase 3 Ember-3 trial, the Inluriyo-Verzenio combo yielded better results in that patient subgroup. For the Inluriyo-Verzenio combo, the trial assessed outcomes against Inluriyo monotherapy.When Inluriyo was initially cleared by the FDA in September, Lilly said it would share a more mature analysis of the combo with the FDA. The 2nd-line fightAn updated analysis from the Ember-3 trial shows the two-drug combo reduced the risk of progression or death by 41% compared with Inluriyo alone in a group of previously treated patients regardless of their ESR1 status, according to results presented at the 2025 San Antonio Breast Cancer Symposium (SABCS).Patients with and those without ESR1 mutations appeared to have benefited from the combo. The ESR1-mutant group logged a progression-free survival improvement of 51%, while the effect size was smaller, at 36%, in patients without the biomarker. None of those numbers bear statistical significance because the study had already met the statistical bar during the primary analysis, which recorded a 43% PFS benefit for the combo in all patients. But, while the combo’s performance in the ESR1 subgroup improved from 47% at the primary analysis, its results deteriorated from 41% in the nonmutant population. At the current second interim analysis with 14 months of additional follow-up from the first, the trial didn’t achieve a high prespecified threshold for significance on overall survival. At 33% data maturity, Inluriyo and Verzenio showed a favorable trend toward an 18% OS improvement in the overall population, with the duo’s advantage over single-agent Inluriyo starting to show after two years. No breakdown of OS data by patients' ESR1 status was offered.But, as Van Naarden hinted when commenting about common FDA practice, “when the effect size is enriched in a subpopulation that’s identifiable, that’s where the agency wants to go.” Lilly’s acknowledgement of defeat in an all-comers second-line population could hand rival Roche a win. But Van Naarden doesn’t think so.Similar to Ember-3’s combo arm, Roche’s evERA trial recently found that the Swiss pharma’s oral SERD candidate giredestrant, used alongside everolimus (Novartis’ Afinitor), significantly lowered the risk of progression or death by 44% versus everolimus alone in patients with second-line ER-positive, HER2-negative breast cancer. Based on the results, Roche is pushing for an all-comers label.But the regimen’s benefit similarly appeared to be mostly driven by the ESR1-mutant group, which logged a 62% PFS improvement. The ESR1 wild-type patients who received the Roche combo only saw a minor 16% difference on PFS, according to an exploratory analysis. An immature OS analysis produced a 21% trend in favor of the combo in the wild-type group, which Roche argued was clinically meaningful.“We’ve seen this exact movie before. It’s not going to end differently,” Van Naarden said, suggesting that Roche will end up with an ESR1-mutant label, too. He was referring to how Menarini’s first-in-class oral SERD, Orserdu, also only secured an ESR1-mutant label even though its pivotal study, Emerald, showed a benefit in an all-comers population. An exploratory analysis found a weak 14% advantage on PFS in patients without ESR1 mutations. The fight beyond 2nd lineWith these data, Van Naarden argued that the second-line setting is “done and dusted” for oral SERDs to be simply ESR1-mutant drugs.Meanwhile, Roche has a first-line trial, pionERA, which is pitting giredestrant against AstraZeneca’s injectable SERD Faslodex, both combined with a CDK4/6 inhibitor, in patients who developed resistance to prior endocrine therapy as adjuvant treatment for early-stage breast cancer.Van Naarden, calling the future outcome of that first-line study “a big unknown,” instead highlighted efforts in the adjuvant setting, which he said the entire oral SERD class was really meant for.There, Roche is currently one step ahead. At SABCS, the Swiss drugmaker reported that, in the phase 3 lidERA trial, giredestrant led to a 30% reduction in the risk of invasive disease recurrence or death versus endocrine therapy when used as an adjuvant therapy after surgery for early-stage breast cancer. RELATEDRoche links oral SERD to 30% breast cancer risk reduction in phase 3 adjuvant trialTo counter Roche’s offering, Lilly is running the Ember-4 trial, which is different from lidERA in that it’s being conducted in patients who have previously received two to five years of adjuvant endocrine therapy. More importantly, participants are allowed to have received a CDK4/6 inhibitor. With that design, Ember-4 is effectively testing Inluriyo in a post-CDK4/6 setting, as adjuvant Verzenio is given for up to two years alongside endocrine therapy, and Novartis’ Kisqali is dosed for three years.In lidERA, only a short course of up to 12 weeks of CDK4/6 inhibitor therapy prior to randomization is allowed.With target enrollment of 8,000 patients, Ember-4 will be Lilly’s largest oncology trial in the company’s history, according to Van Naarden. Following all the positive oral SERD readouts, Van Naarden said he now has increased confidence that the study will be successful.“I think that study will work, and I think it will be a lot more relevant clinically than the Roche study that is reading out now,” Van Naarden said. “In second line, I think the medicine can help people. But I think we can all agree that, if you have the opportunity to increase the cure fraction of an early-stage disease setting, that is more important than prolonging survival in a late-stage setting.”

Phase 3Clinical ResultASCO

11 Dec 2025

·www.prnewswire.com

The PHERGuide study demonstrates the utility of circulating tumor DNA for the early detection and real-time monitoring of localized HER2+ breast cancer

The results of the PHERGuide study, presented during the 2025 San Antonio Breast Cancer Symposium (SABCS), demonstrate that the presence of circulating tumor DNA (ctDNA) is associated with disease stage. This research paves the way for the use of blood-based ctDNA as a non-invasive tool to determine disease status in real-time and achieve greater treatment personalization. During the congress, the design of the PONTIAC study was also presented, which evaluates trastuzumab deruxtecan (T-DXd) as a possible new first-line treatment in HR+ and HER2-low/ultralow breast cancer with a non-luminal subtype. SAN ANTONIO, Dec. 11, 2025 /PRNewswire/ -- MEDSIR, a leading international company in oncology research, has announced the results of the PHERGuide study during the 2025 San Antonio Breast Cancer Symposium (SABCS). This research, presented as an oral session during the congress, corresponds to a translational analysis of the PHERGain study and evaluates the correlation between the presence of circulating tumor DNA (ctDNA) in the blood of the patients, with the response to treatment and the risk of recurrence in patients with HER2+ early breast cancer. Continue Reading Dr. Antonio Llombart-Cussac during the PHERGuide presentation at SABCS 2025 With more than 250 samples analyzed, the results show a direct association between the levels of ctDNA in blood at the start of the study and the stage of the disease. Furthermore, this study also reveals a significant correlation between ctDNA and the response to treatment. After two cycles of therapy, an elimination of ctDNA was observed in 75% of the patients; before surgery, these values reached a negativization of 83%. Consistently, the patients who presented elimination of ctDNA showed a higher probability of responding to the treatment. Notably, patients without ctDNA at the start of the study or who achieved its elimination before surgery, showed a notably more favorable prognosis, with a probability of developing invasive disease between four and five times lower during a follow-up period of three years. "This finding opens the way for us to the utilization of liquid biopsy as a non-invasive tool to know the status of the patients' disease," highlighted Dr. Antonio Llombart-Cussac, principal investigator of the study and Head of the Oncology Service at the Hospital Arnau de Villanova in Valencia, Spain. "In this way, by being able to know the status and response of the disease in real time, we could make more personalized and efficient treatment decisions for the patients," he added. Advances in breast cancer: PONTIAC and CEBBRAH MEDSIR's activity at SABCS 2025 has also included the presentation of the PONTIAC and CEBBRAH studies. PONTIAC is a Phase II trial evaluating the efficacy and safety of the use of trastuzumab deruxtecan (T-DXd) as a first-line treatment for patients with HR+/HER2-low/ultralow breast cancer and a non-luminal genomic subtype. This type of cancer is characterized by having lower sensitivity to hormonal therapy, which is the current standard of treatment for this subgroup of patients; therefore, their therapeutic options are limited. T-DXd is a next-generation therapy that combines two components into a single drug: trastuzumab, an antibody that specifically identifies the HER2 protein present on cancer cells, and deruxtecan, a potent chemotherapeutic drug. This design allows for a selective delivery of the chemotherapy payload into cancer cells, maximizing the anti-tumor effect and minimizing damage to healthy cells and, consequently, reducing side effects. "The design of the PONTIAC study is innovative and highly promising, as it offers a new targeted treatment option for patients with HR+ and HER2- breast cancer with a non-luminal subtype. The objective is to demonstrate whether this represents a more effective and less harmful treatment alternative", highlighted Dr. Javier Cortés, principal investigator of the study, Head of the International Breast Cancer Center in Madrid and Barcelona, Spain. During the congress, MEDSIR also presented the results of the CEBBRAH translational analysis, which evaluates for the first time the presence of ctDNA in both plasma and cerebrospinal fluid of patients with HER2+ breast cancer and leptomeningeal disease treated with T-DXd. The patients who, after receiving T-DXd, showed a reduction of ctDNA in the cerebrospinal fluid presented better control of the leptomeningeal disease, which supports its possible role as a biomarker of the disease. MEDiscussion: ctDNA and other new trends in breast cancer research Within the framework of the congress, MEDSIR held a meeting to debate and analyze the new trends in oncological research. The event featured presentations by three international leaders in oncology: Dr. Antonio Llombart-Cussac, Head of Service at Hospital Arnau de Villanova in Valencia; Dr. Javier Cortés, Director of the International Breast Cancer Center-Pangaea Oncology in Barcelona; and Dr. Naoto Ueno, Director of the University of Hawaii Cancer Center. The session was moderated by Dr. Giampaolo Bianchini, a leading specialist in breast oncology at the Clinical Oncology Department of the Ospedale San Raffaele in Milan, and included the participation of an expanded panel of prominent international oncologists in an open debate together with a specialized audience. Specifically, the debate addressed the relevance of implementing new molecular tools in the clinic, such as ctDNA, for the management of luminal HER2+ breast tumors, as well as the growing role of translational research in the advancement towards precision oncology that improves the patients' quality of life. The Phase III ADELA and TUXEDO-3 studies, also present at SABCS 2025 The company has also presented a poster in a highlighted session regarding a sub-analysis of its TUXEDO-3 study, a multicenter and international Phase II trial that has demonstrated the potential of the antibody-drug conjugate patritumab deruxtecan (HER3-DXd) in patients with brain metastases derived from HER2+ breast cancer [and] advanced non-small cell lung cancer, as well as in patients with leptomeningeal disease of any solid tumor. Now, this sub-analysis examines the efficacy of this drug in those patients with metastatic HER2-positive breast cancer who had already received another type of antibody-drug conjugate in previous lines of treatment. The results point towards a potential strategy of sequential antibody-drug conjugate treatment, by demonstrating the benefit of the use of HER3-DXd in these patients with a median overall survival of 8.1 months, as well as a median progression-free survival of 6.3 months evaluated for intracranial lesions, 11.3 months evaluated for extracranial lesions, and 6.3 months evaluated for combined lesions. Furthermore, the ADELA study, an international Phase III clinical trial, was also present at the SABCS 2025 congress. This study is evaluating a new treatment approach that combines elacestrant with everolimus in a broad group of patients with advanced ER+/HER2- breast cancer and mutations in the ESR1 gene. About MEDSIR Established in 2012, MEDSIR distinguishes itself by its close collaboration with strategic partners to drive innovation in oncological research. With headquarters in Spain and the United States, the company manages the comprehensive management of clinical trials, covering from the study design to its subsequent publication, counting on an extensive global network of experts and integrated technology to streamline the process. The company offers support for proof of concept and a strategic approach that allows research partners to benefit from the best of both worlds: industry clinical research and investigator-driven trials. With the objective of promoting independent research at a global level, MEDSIR has established a strategic alliance with Oncoclínicas, the leading oncological group in Brazil with outstanding research potential in South America. For more information: SOURCE MEDSIR 21% more press release views with Request a Demo

Clinical ResultPhase 2Phase 3ASCO

08 Dec 2025

·www.globenewswire.com

Menarini Group Presents Elacestrant (ORSERDU®) Phase 2 Combination Data in Patients with ER+, HER2- Metastatic Breast Cancer (mBC) at the 2025 San Antonio Breast Cancer Symposium

In addition, the expansive elacestrant clinical development program updates reinforce its potential as a backbone endocrine therapy in combination settings, as well as in both metastatic and early stage breast cancer. FLORENCE, Italy and NEW YORK, Dec. 08, 2025 (GLOBE NEWSWIRE) -- 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 meaningful median progression-free survival (mPFS) efficacy results from two combination regimens of the Phase 2 ELEVATE study in patients with estrogen receptor-positive (ER+), HER2-negative (HER2-) locally advanced or metastatic breast cancer (mBC). The ELEVATE study was designed to evaluate the safety and efficacy of oral-oral combination treatment options to overcome different resistance mechanisms observed in ER+/HER2- mBC with the goal of improving patient outcomes. These data will be presented at the 2025 San Antonio Breast Cancer Symposium (SABCS), December 9-12. “The encouraging progression-free survival data increase our confidence in the role elacestrant could play as an endocrine therapy backbone in the combination setting,” said Virginia Kaklamani, MD, DSc, Professor of Medicine in the Division of Hematology/Oncology at UT Health San Antonio, and Leader of the Breast Cancer Program at UT Health San Antonio MD Anderson Cancer Center. “The safety profile of elacestrant in combination with everolimus or abemaciclib is consistent with the known safety profiles of each drug. No new safety signals have been observed.” The ELEVATE data to be presented at SABCS demonstrate that elacestrant in combination with everolimus or with abemaciclib shows a consistent PFS benefit, irrespective of ESR1 mutation status in patients with ER+/HER2- mBC, who experience disease progression on endocrine therapy (ET), with or without prior exposure to CDK4/6 inhibitors. These updated results also show that the safety of the combinations are consistent with the known safety profiles of each targeted therapy plus standard of care endocrine therapy. Phase 2 mPFS in months (95% CI) in all patients and subgroups Patient Population Elacestrant 345 mg QD+ Everolimus 7.5mg QD(n=50)Elacestrant 345 mg QD+ Abemaciclib 150 mg BID(n=60)All patients 8.3 [4.0 – 10.2]14.3 [7.3-16.6]Visceral disease 7.7 [3.8 – 9.4]14.3 [7.4-16.6]No prior fulvestrant 8.3 [4.2 – 12.9]14.8 [8.7-NR]No primary endocrine resistance 8.3 [4.0-12.9]14.3 [7.3-16.6]ESR1mut 8.7 [3.5 – 12.9]*ESR1wt 9.0 [4.2 – 12.7]*PIK3CAmut 8.3 [3.6 - 10.2]*PIK3CAwt 9.6 [5.6 - NR]* *Maturity not reached for PFS (95% CI) for genomic subgroups (ESR1 / PIK3CA) in the elacestrant + abemaciclib cohort. “The extensive evidence for elacestrant spans the monotherapy setting in our pivotal EMERALD study, now backed by two recent real-world data publications1, 2, and in its growing potential in combination regimens, as highlighted by the data presented at SABCS,” said Elcin Barker Ergun, CEO of the Menarini Group. “We remain deeply committed to fully exploring elacestrant’s potential benefit across multiple ongoing trials in both early stage and metastatic breast cancer.” Additionally, other elacestrant updates will be presented at SABCS, investigating its potential across the spectrum of breast cancer: Presentation Title: Elacestrant in combination with everolimus or abemaciclib in patients with ER+/HER2-locally advanced or metastatic breast cancer (mBC): phase 2 results from ELEVATE, an open-label, umbrella studyAbstract Number: 1255Presentation Date & Time: Thursday, December 11, 2025, 1:00 – 2:00 PM Location: Hemisfair1-2Presenting Author: Hope S. Rugo Presentation Title: Elacestrant alone or in combination with triptorelin in premenopausal women with ER+/HER2-early breast cancer: primary analysis from the phase 2 SOLTI-2104-PremiÈRe trialAbstract Number: 1123Presentation Date & Time: Friday, December 12, 2025, 7:30 – 7:33 AMLocation: 301 ABCPresenting Author: Mertixell Bellet Presentation Title: ELEGANT: Elacestrant Versus Standard Endocrine Therapy (ET) in Women and Men With Node-positive, Estrogen Receptor-positive (ER+), HER2-negative (HER2-), Early Breast Cancer (eBC) With High Risk of Recurrence in a Global, Multicenter, Randomized, Open-label Phase 3 Study.Abstract Number: 1276Presentation Date & Time: Thursday, December 11, 2025, 12:30 – 2:00 PMLocation: Henry B. Convention CenterPresenting Author: Aditya Bardia Presentation Title: The ADELA study: A Double-blind, Placebo-controlled, Randomized Phase 3 Trial of Elacestrant (ELA)+ Everolimus (EVE) Versus ELA + Placebo (PBO) in ER+/HER2-Advanced Breast Cancer (aBC) Patients with ESR1-mutated Tumors Progressing on Endocrine Therapy (ET) + CDK4/6iAbstract Number: 1141Presentation Date & Time: Wednesday, December 10, 2025, 12:30 – 2:00 PMLocation: Henry B. Convention CenterPresenting Author: Antonio Llombart-Cussac Presentation Title: ERADICATE: A phase Ib/II study of elacestrant plus trastuzumab deruxtecan in patients with CDK4/6 inhibitor and endocrine-resistant HR+/HER2-low or HER2-ultralow metastatic breast cancerAbstract Number: 2119Presentation Date & Time: Friday, December 12, 2025, 12:30 – 2:00 PMLocation: Henry B. Convention CenterPresenting Author: Sara L. Sammons Presentation Title: Hormonal receptor (HR)-positive HER2 negative breast cancer patients treated with preoperative Elacestrant and PULSAR adaptive radiotherapy: a phase II study (HELP Trial)Abstract Number: 1071Presentation Date & Time: Friday, December 12, 2025, 12:30 – 2:00 PMLocation: Henry B. Convention CenterPresenting Author: Luca Visani About The Elacestrant Clinical Development ProgramElacestrant 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 InformationWarning 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 GroupThe Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of $5 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 bringing transformational oncology treatments to patients. Stemline commercializes elacestrant, 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, in the U.S., Europe, and other global regions. Stemline also commercializes tagraxofusp-erzs, a novel targeted therapy directed to CD123, for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic cancer, in the United States, Europe, and other global regions. In addition, Stemline commercializes selinexor, an XPO1 inhibitor for multiple myeloma, in Europe. The company is also conducting multiple label-expansion studies with elacestrant and tagraxofusp in breast and hematologic cancer indications, respectively, and has an extensive clinical pipeline of additional drug candidates in various stages of development for a host of solid and hematologic cancers. Media ContactsThe Menarini GroupValeria Speroni CardiEmail: pressoffice@menarini.com Stemline Therapeutics, Inc.Cheya PopeEmail: media@menarinistemline.com 1 Lloyd et al. Clinical and genomic factors associated with elacestrant outcomes in ESR1-mutant metastatic breast cancer. Clin Cancer Res (2025). https://aacrjournals-org.libproxy1.nus.edu.sg/clincancerres/article/doi/10.1158/1078-0432.CCR-25-3033/768341/Clinical-and-Genomic-Factors-Associated-with 2 Rugo et al. Real-World Outcomes of Elacestrant in ER+, HER2-, ESR1-mutant Metastatic Breast Cancer. Clin Cancer Res, 2025. CCR-25-3040R1. https://aacrjournals-org.libproxy1.nus.edu.sg/clincancerres/article/doi/10.1158/1078-0432.CCR-25-3040/768340/Real-World-Outcomes-of-Elacestrant-in-ER-HER2-ESR1

Phase 2Phase 3Clinical Result

100 Deals associated with Elacestrant hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D11671	Elacestrant hydrochloride	-	DB06374

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Advanced breast cancer	United Kingdom	Stemline Therapeutics, Inc.	05 Jan 2024
Metastatic breast cancer	United Kingdom	Stemline Therapeutics, Inc.	05 Jan 2024
ER-positive/HER2-negative/ ESR1-mutated breast cancer	United States	Stemline Therapeutics, Inc.	27 Jan 2023

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Breast Cancer	NDA/BLA	United States	Radius Pharmaceuticals, Inc.	22 Jun 2022
Hormone receptor positive HER2 negative breast cancer	Phase 3	-	Berlin-Chemie/Menarini Pharma GmbH	31 Jan 2026
Node-positive breast cancer	Phase 3	United States	Stemline Therapeutics, Inc.	27 Sep 2024
Node-positive breast cancer	Phase 3	Argentina	Stemline Therapeutics, Inc.	27 Sep 2024
Node-positive breast cancer	Phase 3	Australia	Stemline Therapeutics, Inc.	27 Sep 2024
Node-positive breast cancer	Phase 3	Austria	Stemline Therapeutics, Inc.	27 Sep 2024
Node-positive breast cancer	Phase 3	Belgium	Stemline Therapeutics, Inc.	27 Sep 2024
Node-positive breast cancer	Phase 3	Brazil	Stemline Therapeutics, Inc.	27 Sep 2024
Node-positive breast cancer	Phase 3	Canada	Stemline Therapeutics, Inc.	27 Sep 2024
Node-positive breast cancer	Phase 3	Czechia	Stemline Therapeutics, Inc.	27 Sep 2024

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06492616 (ELEGANT, SABCS2025)	Phase 3	ER-positive/HER2-negative Breast Cancer ESR1-mut \| ER+ \| HER2-	4,220	Elacestrant	xnapwqbrwx(bxdgpcdcff) = xexwixgwqp jltmvoltpl (cbiwwhopsf )	Positive	11 Dec 2025
SABCS2025	Not Applicable	Hormone receptor positive breast cancer PIK3CA \| ESR1	107	alpelisib+fulvestrant	spionhxtri(vdwvqxisbl) = One patient with alpelisib experienced treatment interruption and dose reduction due to skin toxicity, while Elacestrant was well-tolerated without major adverse effects. xifjywisjo (utrjdeecqd )	Positive	10 Dec 2025
				capivasertib+fulvestrant
NCT06382948 (ADELA, SABCS2025)	Phase 3	ESR1-mutated \| ER+/HER2-	240	Elacestrant + Everolimus	flrtzwlnnm(ddqhifzsdi) = oaerwtkmbp azpldgshvw (pvhiiskxjj )	Positive	10 Dec 2025
				Elacestrant + Placebo	qjgbqqqyoc(oxgluvivme) = gyjggtfpwb vxfbksmzth (zhhnlxbcet )
ESMO2025	Not Applicable	Advanced breast cancer HR+ \| HER2-	16	Camizestrant	-	Positive	17 Oct 2025
				Ribociclib plus ET
NCT06382948 (ADELA, ASCO2025)	Phase 3	ER-positive/HER2-negative/ ESR1-mutated breast cancer \| HER2-negative breast cancer \| Estrogen receptor positive breast cancer ... ESR1-mutated tumors View more	240	Elacestrant 345 mg + Everolimus 7.5 mg	otdejqryrz(jgwayominx) = wpwsiaoojx todvopncre (koghrextor ) View more	Positive	30 May 2025
NCT05563220 (ELEVATE, ASCO2025)	Phase 1/2	ER-positive/HER2-negative Breast Cancer	-	Elacestrant + Ribociclib	ptlesmjclc(dnzbuyywhb) = 43% (7% ≥Gr3) with Ela + Eve ggllppyltk (xkdwldkxta ) View more	-	30 May 2025
				Elacestrant + Everolimus
NCT06492616 (ELEGANT, ASCO2025)	Phase 3	Node-positive breast cancer \| Estrogen receptor positive breast cancer Adjuvant Ki67	-	Elacestrant	riuriguefe(wrbfrguefe) = skjvlodhxs gileybwjas (xivrvlnaig )	Positive	30 May 2025
				Standard Endocrine Therapy (AI or tamoxifen)	riuriguefe(wrbfrguefe) = dlqdamkzwm gileybwjas (xivrvlnaig )
NCT03778931 (EMERALD, ESMO_BC2025)	Phase 3	Metastatic breast cancer ESR1	966	elacestrant (ESR1 mutation testing by liquid biopsy using ddPCR)	akjmujacpo(cfqrmzfbpy) = wxbeknarla podupelhow (wikjvofceb, 33.2% - 39.4) View more	Positive	14 May 2025
NCT05563220 \| NCT05386108 (ELEVATE, SABCS2024) Manual	Phase 1/2	ER-positive/HER2-negative Breast Cancer HER2 Negative	55	Elacestrant + Abemaciclib (all efficacy-evaluable)	swdyhclote(qfrnvantba) = dkqrozdjle ydslojjpwh (grgpdbbwnz )	Positive	10 Dec 2024
				Elacestrant + Abemaciclib (ESR1-mut population)	swdyhclote(qfrnvantba) = nnirklfmnt ydslojjpwh (grgpdbbwnz )
SABCS2024 Manual	Not Applicable	ER-positive/HER2-negative Breast Cancer HER2 Negative	212	Elacestrant	gipfsvwped(huouqkdfrl) = djmtaximgp xawwnofhzp (cijiobufrg, 5.4 - NR)	Positive	10 Dec 2024
				Elacestrant (1-2 lines of prior ET)	gipfsvwped(huouqkdfrl) = efbwpraqkn xawwnofhzp (cijiobufrg, 4.9 - NR)

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