Orserdu (elacestrant) / Radius, Menarini, DRI Healthcare, SciClone - LARVOL DELTA

Pharmacological Insights on USFDA-Approved Novel Drug Therapies in the Year 2023. (PubMed, Curr Drug Discov Technol) - "The novel drug therapies approved by the USFDA hold significant potential to enhance the patient's care by providing advanced treatment modalities. This manuscript, reporting the comprehensive description of therapeutic aspects of the mentioned new drug therapies, underscores the commitment of the pharmaceutical sector to address the unmet medical needs and reshape the landscape of the healthcare service system by instilling optimism among patients and healthcare providers."

FDA event • Journal • Pediatrics • Rare Diseases

Clinical investigators' (CIs) practice patterns for patients with hormone receptor-positive metastatic breast cancer (HR+ mBC) harboring PI3K/AKT/PTEN pathway abnormalities (PAPm). (ASCO 2025) - "The recent availability of capi and inavo has significantly affected current practice patterns, with the majority of CIs rapidly incorporating these therapies into their treatment algorithms for specific patient types. Future work is needed to explore how other factors (eg, age, comorbidities, HER2-low status) and rapidly emerging clinical trial findings (eg, EMBER-3) affect decision-making. A = anastrozole; IPF = inavolisib + palbociclib + fulvestrant; F = fulvestrant; AI = aromatase inhibitor; C = capivasertib; Alp = alpelisib; E = elacestrant"

Clinical • Metastases • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA • PTEN

The impact of ethnicity on benefit from novel drugs approved for breast cancer treatment: a systematic review and meta-analysis of randomized phase 3 trials of the last decade. (SABCS 2024) - "23 phase III RCTs were identified in the aBC setting, with 1547 (11.1%) patients of Asian ethnicity. Experimental drugs tested included CDK4/6i (palbociclib, ribociclib, abemaciclib), SERD (elacestrant), PI3Ki (alpelisib), PARPi (olaparib, talazoparib), broad variety of anti-HER2 drugs (tucatinib, trastuzumab deruxtecan, pertuzumab, T-DM1, neratinib, margetuximab), anti-PD-1 and anti-PD-L1 drugs (pembrolizumab, atezolizumab) and anti-TROP2 drug (sacituzumab govitecan). 16 RCTs provided HR (95%CI) for PFS in the subgroup of Asians and 17 RCTs for Non-Asians."

IO biomarker • P3 data • Retrospective data • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Elacestrant combinations in patients (pts) with ER+/HER2- locally advanced or metastatic breast cancer (mBC): Safety update from ELEVATE, a phase (Ph) 1b/2, open-label, umbrella study. (ASCO 2025) - P1/2 | "ELEVATE (NCT05563220) evaluates Ela in combination with everolimus (Eve), alpelisib (Alp), capivasertib (Capi), ribociclib (Ribo), palbociclib (Palbo), or abemaciclib (Abema) to address different resistance mechanisms. Elacestrant combinations continue to demonstrate safety consistent with the known profiles of each drug + SOC ET without increased risk of associated AEs. Elacestrant has the potential to become an ET backbone for multiple targeted agents, providing an all-oral treatment option in pts with ER+/HER2- mBC, delaying chemo or ADC-based regimens. Treatment-emergent AEs (≥30%).*Combined terms; †Maculopapular rash."

Clinical • Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Elacestrant (Ela) combinations with ribociclib (Ribo) and everolimus (Eve) in patients (pts) with ER+/HER2- locally advanced or metastatic breast cancer (mBC): Update from ELEVATE, a phase (Ph) 1b/2, open-label, umbrella study. (ASCO 2025) - P1/2 | " ELEVATE evaluates Ela in combination with everolimus (Eve), alpelisib (Alp), capivasertib (Capi), ribociclib (Ribo), palbociclib (Palbo), or abemaciclib (Abema) to address different resistance mechanisms. Elacestrant plus Ribo or Eve demonstrates promising Ph 1b efficacy in pts with ER+/HER2- mBC with progressive disease after ET+CDK4/6i in all patients. Ela 345 mg + Ribo 400 mg QD was determined as the RP2D. Previously, Ela 345 mg + Eve 7.5 mg was identified as the RP2D."

Clinical • Metastases • P1/2 data • Breast Cancer • Dental Disorders • Fatigue • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • Stomatitis • CDK4 • ER • HER-2

Targeted agents for the treatment of hormone receptor–-positive, human epidermal growth factor receptor 2–negative metastatic breast cancer (HR+/HER2- MBC) with co-alterations in ESR1 and AKT pathway: A retrospective analysis. (ASCO 2025) - "Tumors with an ESR1m are targeted with elacestrant (E), and those with alterations in PIK3CA, AKT, or PTEN are candidates for capivasertib (C) or, if PIK3CAm, alpelisib (A). In this real-world cohort, pts with HR+/HER2- MBC with co-alterations in ESR1 and AKT pathway, mTOT was longest with A, with the caveat that A treated pts received the fewest prior lines of therapy. mOS was significantly longer in those who received E vs those who did not. Analysis of pts receiving E+A/C was limited by small sample size and optimal sequencing should be studied in randomized prospective clinical trials."

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA • PTEN

Lasofoxifene acts as a selective agonist in the bone microenvironment (ENDO 2025) - P3 | "ELAINE-III [NCT05696626] is a clinical trial currently investigating the efficacy of lasofoxifene and abemaciclib compared to fulvestrant abemaciclib combination therapy for advanced or metastatic ER+ breast cancer with an ESR1-mutation...Additionally, drug synergism studies with lasofoxifene and the NCI NExT Oncology Interrogation Tools Set of 555 drugs were performed to identify pathways which were vulnerable in Elacestrant-treated cells. This data will translate into novel treatment combinations which are targeted to bone metastasis in pre-clinical models. This study has determined that lasofoxifene is protective in the bone microenvironment, unlike other new-generation endocrine therapies, and future directions include evaluating the ramifications of this activity on bone metastasis progression."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER

Lasofoxifene acts as a selective agonist in the bone microenvironment (ENDO 2025) - P3 | "ELAINE-III [NCT05696626] is a clinical trial currently investigating the efficacy of lasofoxifene and abemaciclib compared to fulvestrant abemaciclib combination therapy for advanced or metastatic ER+ breast cancer with an ESR1-mutation...Additionally, drug synergism studies with lasofoxifene and the NCI NExT Oncology Interrogation Tools Set of 555 drugs were performed to identify pathways which were vulnerable in Elacestrant-treated cells. This data will translate into novel treatment combinations which are targeted to bone metastasis in pre-clinical models. This study has determined that lasofoxifene is protective in the bone microenvironment, unlike other new-generation endocrine therapies, and future directions include evaluating the ramifications of this activity on bone metastasis progression."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER

ELCIN: ELACESTRANT in Women and Men With CDK4/6 Inhibitor-Naive Estrogen Receptor Positive, HER-2 Negative Metastatic Breast Cancer Study (clinicaltrials.gov) - P2 | N=61 | Active, not recruiting | Sponsor: Stemline Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

HELP: Hormonal Receptor (HR)-Positive HER2 Negative Breast Cancer Patients Treated With Preoperative ELacestrant and PULSAR Radiotherapy (clinicaltrials.gov) - P2 | N=21 | Not yet recruiting | Sponsor: Azienda Ospedaliero-Universitaria Careggi

New P2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

ELCIN: Elacestrant in women and men with CDK4/6 inhibitor (CDK4/6i)-naïve estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (mBC)—An open-label multicenter phase 2 study. (ASCO 2025) - P2 | "Exploratory objectives include elacestrant efficacy according to ESR1-mut status, changes in biomarkers, including allele mutation frequencies (cfNAs), and relationship between efficacy endpoints. Status: ELCIN has a planned sample size of 60 patients; recruitment is ongoing worldwide."

Clinical • Metastases • P2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • mTOR

Therapeutic impact of novel agents in patients with stage IV de novo HR+ve/Her2-ve breast cancer: Results from a real world dataset. (ASCO 2025) - "Compared to pts receiving palbo median OS was signficantly better among pts receiving abema (HR 0.77; 95%CI (0.69,0.85) p<0.0001) or ribociclib (HR 0.69; 95%CI (0.60,0.81) p<0.0001)...Among patients treated with CDK4/6i, OS was significantly longer among pts who received elacestrant vs those who did not (HR 0.401; 95%CI (0.215,0.745)...5yr OS was 76.2% vs 52.7% among those who did and did not receive Trastuzumab deruxtecan respectively (HR 0.37, 95%0.19,0.70)... Among pts with stage IV Denovo HR+ve/HER2-ve BC treated with a CDK4/6i using a CDK4/6i beyond progression is an option. Novel agents such as oral SERDS and ADCs are also associated with improved prognostic outcome in the real world setting."

Clinical • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • HER-2

ADELA: 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) + CDK4/6i. (ASCO 2025) - P1/2, P3 | "Patients will receive dexamethasone mouthwash during the first 8 wks. Secondary endpoints include investigator-assessed PFS, OS, ORR, CBR, DoR, TTR, best percentage change in tumor burden, safety, and HRQoL. Status: Planned enrollment is 240 patients; recruitment is ongoing."

Clinical • Metastases • P3 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Immunologic targeting of native and mutated ESR1 receptor for treatment of hormone receptor expressing metastatic breast cancer. (ASCO 2025) - P1 | "Combining DC1 vaccination with novel endocrine therapies such as Elacestrant, we expect an increase in ESR1 degradation and enhanced antigen presentation leading to an expanded immune and clinical response...The study is open at H. Lee Moffitt Cancer Center. Clinical trial information: NCT06691035"

Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CD4 • ER • HER-2

EORTC-2129-BCG: Elacestrant for treating ER+/HER2- breast cancer patients with ctDNA relapse (TREAT ctDNA). (ASCO 2025) - P3 | "Study conducted under the Breast International Group (BIG) umbrella. Collaborative groups: GIM, CTI, SUCCESS, SOLTI, HeCOG, HORG, BOOG, SweBCG and ETOP-IBCSG."

Circulating tumor DNA • Clinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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. (ASCO 2025) - P3 | " ELEGANT (NCT06492616) is a global, multicenter, open-label phase 3 study designed to evaluate elacestrant vs SOC ET (AI or tamoxifen) in patients with eBC and a high risk of recurrence. Key secondary endpoints include distant relapse-free survival, overall survival, invasive disease-free survival, safety, patient-reported outcomes-quality of life, and pharmacokinetics. Status: Planned enrollment is 4,220 patients; recruitment is ongoing."

Clinical • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Inflammatory Breast Cancer • Oncology • Solid Tumor • ER • HER-2

PML1-Mediated Feedforward Loop Through PI3K and MAPK Axes Drives Endocrine Resistance. (PubMed, bioRxiv) - "Endocrine resistance remains a major obstacle in treating estrogen receptor-positive metastatic breast cancer. Our study identifies PML1 as a central mediator of this resistance, revealing how it maintains a self-reinforcing signaling network through PI3K and MAPK pathways by enhancing the production of cytokines and growth factors. The clinical significance of our findings is threefold: we establish PML1 as a biomarker for therapy resistance, demonstrate its mechanistic role in treatment failure, and show that FDA-approved arsenic trioxide can disrupt PML1-driven resistance. These insights provide a direct path to clinical translation, as combining arsenic trioxide with existing therapies could benefit patients with limited treatment options."

Journal • Breast Cancer • Endocrine Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • HBEGF

Importance of MTB network for liquid biopsy-based testing and treatment recommendations in metastatic breast cancer in Austria (OeGHO-AHOP 2025) - "The approval of the selective estrogen receptor degrader (SERD) Elacestrant for treatment of hormone receptor positive, metastatic breast cancer (HR+ mBC) with ESR1 mutations highlighted the need for structured testing and interpretation, even in early treatment lines... The ESR1 project demonstrated a feasible strategy to implement precision medicine based on ctDNA in clinical routine. The context of MTB enables a structured assessment of clinical relevance of detected mutations."

Biopsy • Liquid biopsy • Metastases • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • ER • PIK3CA

Pathogenic ESR1 mutations in patients with HR+, HER2- metastatic breast cancer (OeGHO-AHOP 2025) - "Introduction and aims: Elacestrant is the first selective estrogen recepetor degrador (SERD) approved for treatment of metastatic hormone receptor positive HER2 negative breast cancer (HR+, HER2- mBC) harboring an ESR1 mutation... ESR1 mutations in this heterogenous cohort were detected in 22.6% of patients. The most common ESR1 mutations were D538G, Y537S, E380Q and Y537N comparable to previously reported trials."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AVEN • ER • HER-2

Umbrella Study Looks at Safety and Efficacy of Hormone Therapy Combination for ER+/HER2 Advanced and Metastatic Breast Cancer (NYU Langone Health) - P1/2 | N=400 | ELEVATE (NCT05563220) | Sponsor: Stemline Therapeutics, Inc. | "The study includes data from the ongoing ELEVATE trial, which evaluates the safety and efficacy of elacestrant combinations. Results show that elacestrant combinations are generally well tolerated, with adverse events consistent with the known profiles of the companion drugs. For example, neutropenia was observed with CDK4/6 inhibitors, while stomatitis and rash were common with everolimus. Importantly, elacestrant did not increase the risk of adverse events when combined with these agents, supporting its use as a backbone for combination therapies. The study highlights elacestrant’s potential to delay the need for chemotherapy or antibody-drug conjugate-based regimens in mBC patients."

P1/2 data • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Menarini Group Presents Updated Data Underscoring the Combinability of Elacestrant (ORSERDU) in Patients with ER+, HER2- Metastatic Breast Cancer (mBC) at the ASCO 2025 Annual Meeting (GlobeNewswire) - P1b/2 | N=400 | ELEVATE (NCT05563220) | Sponsor: Stemline Therapeutics, Inc. | "The Menarini Group...will present updated preliminary efficacy and safety results from the Phase 1b/2 ELEVATE study in patients with estrogen receptor-positive (ER+), HER2-negative (HER2-) locally advanced or metastatic breast cancer (mBC)....ELEVATE results reported at ASCO 2025 (abstract 1070/49) include updated efficacy data which demonstrate favorable preliminary progression-free survival (PFS) from the elacestrant plus ribociclib and the elacestrant plus everolimus cohorts. A recommended phase 2 dose (RP2D) was determined to be elacestrant 345 mg plus ribociclib 400 mg....Additional data reported separately (abstract 1079/58) provided updated Phase 1b/2 safety results from four cohorts of the ELEVATE study, including elacestrant plus ribociclib, everolimus, alpelisib, and capivasertib."

P1/2 data • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

SOLTI-2104: Elacestrant With/Without Triptorelin in Premenopausal Women With Luminal Breast Cancer (clinicaltrials.gov) - P2 | N=48 | Active, not recruiting | Sponsor: SOLTI Breast Cancer Research Group | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2025 ➔ Feb 2026 | Trial primary completion date: Oct 2024 ➔ Jun 2025

Enrollment closed • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

ESR1 testing on FFPE samples from metastatic lesions in HR + /HER2- breast cancer after progression on CDK4/6 inhibitor therapy. (PubMed, Breast Cancer Res) - "Testing for ESR1 mutations is essential for guiding treatment with novel oral selective estrogen receptor degraders (SERDs) like elacestrant or camizestrant. Co-mutations in actionable pathways, particularly PIK3CA, were observed in n = 10 ESR1 mutant tumors (41.6%), highlighting their contribution to resistance mechanisms and posing significant challenges for treatment selection, as these alterations may necessitate combination therapies to effectively target multiple resistance pathways. This study presents new insights into the prevalence and clinical significance of ESR1 mutations in HR + /HER2- MBC, highlighting the potential utility of FFPE biopsy samples as a viable alternative or complementary approach to LB for mutation detection, particularly in resource-limited settings where access to ctDNA analysis may be constrained."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CCDC170 • ER • HER-2 • PIK3CA

Screening or Early Detection of Brain Metastases and the Treatment in the Era of New Agents (GBCC 2025) - "Advances in systemic therapy have been greatest in HER2-positive breast cancer, where the current NCCN guidelines include a growing list of CNS-active regimens, such as tucatinib-capecitabine-trastuzumab, T-DXd, T-DM1, high dose trastuzumab and pertuzumab, neratinib-capecitabine, and lapatinib-capecitabine...There are a number of novel blood-brain-barrier (BBB) penetrant HER2-targeted tyrosine kinase inhibitors (e.g. ZN1041, IAM1363) in early-phase clinical trials. For patients with HER2-negative tumors, the data are more sparse; however, activity of chemotherapy drugs such as capecitabine, anthracyclines, platinums, and eribulin has been reported...Ongoing clinical trials are testing a wide variety of ADCs, such as patritumab deruxtecan, datopotamab deruxtecan, ARX788, and others...For example, the ELECTRA trial is testing the combination of elacestrant and abemaciclib. Overall, the expanding array of systemic options with clinically meaningful intracranial activity, as..."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2

Oral Selective Estrogen Receptor Degraders (SERDs) improved Progression-free Survival in ER+, HER2- Metastatic Breast Cancer: A Systematic Review and Meta-analysis (ASBrS 2025) - "Until 2023, fulvestrant, administered intramuscularly, was the only SERD available. The approval of elacestrant, the first oral SERD, for patients with ESR1-mutated, ER+/HER2- advanced breast cancer, marks a major therapeutic advance, particularly in combination therapy settings... Oral selective estrogen receptor degraders (SERDs) significantly enhance progression-free survival in patients with estrogen receptor-positive (ER+), HER2-negative advanced breast cancer, particularly in those with ESR1 mutations. The substantial reduction in the risk of disease progression or death emphasizes oral SERDs as a more promising and effective option compared to standard endocrine therapy. These findings highlight the potential of oral SERDs to improve clinical outcomes, especially for patients with ESR1-mutated breast cancers."

Metastases • Retrospective data • Review • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2