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

SUMIT-ELA: A Study of Samuraciclib and Elacestrant in Participants With Metastatic or Locally Advanced HR+/HER2-negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=49 | Completed | Sponsor: Carrick Therapeutics Limited | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • TP53

Safety profile of post-CDK4/6 treatments in HR+/HER2− metastatic breast cancer (mBC): A network meta-analysis (AACR 2026) - "Among ET-based strategies, the lowest RRs were observed for: imlunestrant alone (0.98, 95% CI 0.92-1.05) for any G AEs; camizestrant 75 mg (0.81, 0.36-1.83) for G≥3 AEs; elacestrant (1.45, 0.66-3.16) for AEs leading to discontinuation. While among antibody-drug conjugates (ADCs) the lowest RRs were observed for: sacituzumab govitecan (SG) for any G AEs (1.00, 0.99-1.01); datopotamab deruxtecan (Dato-DXd) (0.47, 0.37-0.59) for G≥3 AEs; SG (0.83, 0.26-2.66) for AEs leading to discontinuation...Among ET-based options, novel mono-ETs (oral SERDs and PROTACs) showed the lowest risk of discontinuation and G≥3 AEs. Among ADCs, TROP2-directed agents had fewer discontinuations, while ADCs with DXd as a payload showed higher rates of any G AEs but (except for DESTINY-Breast06) lower G≥3 AEs risk than other tx strategies."

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. (PubMed, J Clin Oncol) - "Elacestrant is the first oral selective ER degrader demonstrating a significant PFS improvement versus SOC both in the overall population and in patients with ESR1 mutations with manageable safety in a phase III trial for patients with ER-positive/HER2-negative advanced breast cancer."

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

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 trial (SABCS 2025) - P2 | "Ovarian function suppression (OFS) in combination with tamoxifen or aromatase inhibitors improves disease-free survival but has limitations such as toxicity, suboptimal estrogen suppression, and poor adherence. This study provides the first evidence that ELA ± OFS elicits antiproliferative and molecular responses in premenopausal women with ER+/HER2- EBC. Both regimens had comparable and significant reductions in Ki67, CCCA, ROR-P scores, and proliferation gene expression. PremiÈRe trial support the potential role of ELA as a novel ET in this population, potentially sparing the need for OFS."

Clinical • Combination therapy • P2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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 study (SABCS 2025) - " ELEVATE is evaluating elacestrant combined with everolimus, alpelisib, capivasertib, abemaciclib, ribociclib,or palbociclib to address different resistance mechanisms...PFS benefit was consistent across subgroups, including those with visceral metastases, prior fulvestrant or primary ET resistance... Elacestrant in combination shows a consistent PFS benefit irrespective of ESR1m status in pts with ER+/HER2-mBC after progressive disease on ET ± prior CDK4/6i. Elacestrant has the potential to become an ET backbone for combination strategies with targeted agents, supporting an all-oral approach that may delay the need for chemo or ADC-based regimens in this patient population. Table 1:Phase 2 mPFS, mo[95% CI] in all patients and subgroupsNR, not reached"

Clinical • Combination therapy • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • PIK3CA

Phase 1/2 Study to Evaluate EP0062 as Monotherapy and in Combination in Patients With Advanced or Metastatic AR+/HER-2-/ER+ Breast Cancer (clinicaltrials.gov) - P1/2 | N=95 | Recruiting | Sponsor: Ellipses Pharma | N=60 ➔ 95 | Trial completion date: Nov 2026 ➔ Feb 2028 | Trial primary completion date: Nov 2025 ➔ Feb 2028

Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • 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 • HER-2

ADELA: A double-blind, placebo-controlled, randomized phase 3 trial of elacestrant (Ela) + everolimus (EVE) versus elacestrant + placebo in ER+/HER2- advanced breast cancer (aBC) patients with ESR1-mutated tumors progressing on endocrine therapy (ET) + CDK4/6i (AACR 2026) - "Abstract is embargoed at this time."

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

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 (AACR 2026) - "Abstract is embargoed at this time."

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

AZD4241, an orally bioavailable ERα PROTAC, degrades wild-type and mutant ERα and delivers anti-tumour activity in preclinical breast cancer models (AACR 2026) - "Current ER‑pathway inhibitors include aromatase inhibitors (letrozole, anastrozole, exemestane), selective estrogen receptor modulators (SERMs; tamoxifen), and selective estrogen receptor degraders (SERDs; fulvestrant, elacestrant, imlunestrant)...In vivo, AZD4241 induced dose‑dependent anti‑tumour activity and, in some cases, tumour regressions across ESR1wt and ESR1m patient‑derived xenograft (PDX) models, including a palbociclib‑resistant model...Collectively, these data confirm that AZD4241 is a potent, orally bioavailable degrader of wt and mutant ERα, driving anti-tumour efficacy in ESR1wt, ESR1m, and CDK4/6 inhibitor‑resistant PDX models. These findings support the use of AZD4241 as a novel ER-PROTAC with potential to overcome key resistance mechanisms to current standards of care and deliver clinical benefit for patients with ER‑positive breast cancer."

Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CRBN • TFF1

Elacestrant (Ela) in combination with everolimus (Eve) or abemaciclib (Abema) in patients with ER+/HER2- locally advanced or metastatic breast cancer mBC: phase 2 results from ELEVATE, an open-label, umbrella study (AACR 2026) - "Abstract is embargoed at this time."

Clinical • Combination therapy • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Mechanistic characterization of (Z)-endoxifen in ESR1-mutant and endocrine-resistant breast cancer (AACR 2026) - P2 | "(Z)-Endoxifen, the active tamoxifen metabolite, inhibits ER signaling, but its impact on ESR1-mutant signaling and therapy-resistant disease is not yet fully defined. HEK293T cells were transfected with ESR1-WT or mutant plasmids together with an ERE-luciferase reporter and Renilla control. In summary, (Z)-endoxifen and elacestrant both suppress ER-dependent transcription in ESR1-WT and mutant models, and clinically relevant (Z)-endoxifen concentrations are sufficient to inhibit mutant ESR1 activity. Endoxifen additionally reprograms key transcriptional and metabolic pathways associated with ESR1-mutant resistance and metastasis. These results support further evaluation of (Z)-endoxifen's pathway-level effects in ESR1-mutant breast cancer, and ongoing studies are testing its ability to block mutant ESR1-driven proliferation in preclinical models."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ELF3 • ER • FOXA1 • POU5F1 • SOX11 • SPDEF

Cooperative role of ESR1 mutations and midasin in endocrine resistance and the therapeutic potential of dual targeting (AACR 2026) - "Immunoblots demonstrated that elacestrant reduced ER and midasin expression, while the combination produced a synergistic decrease in MDN1, supporting a cooperative mechanism between ER signaling and midasin. Overall, our results indicate that aberrant ESR1 activity and elevated MDN1 cooperate to drive aggressive tumor phenotypes, and that simultaneous inhibition of ER and midasin may offer a novel therapeutic avenue for patients with ESR1-mutant, endocrine-resistant breast cancer."

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

Targeting estrogen receptor mutations and aberrant myelopoiesis in hormone resistant breast cancer (AACR 2026) - "A key mechanism of resistance involves somatic mutations in the ESR1 gene, most commonly Y537S and D538G, which stabilize the ligand-binding domain in a constitutively-active conformation, thereby enabling ligand-independent ER signaling and diminishing effectiveness of aromatase inhibitors and tamoxifen. Until recently, fulvestrant was the only selective estrogen receptor degrader (SERD) available to counteract endocrine resistance; however, two next-generation SERDs, elacestrant and imlunestrant, have now received FDA approval...Furthermore, combining endocrine agents with immunotherapy may help mitigate immune suppressive myeloid populations within the TME and enhance T-cell-mediated anti-tumor responses. Funding: CIRM DISC2-14166, UCLA JCCC BC Award, Tower Cancer Res Found, Hickey Foundation, NIH/NCI U54 CA143930 CDU-UCLA JCCC Partnership, CBCRPB27IB3869, DOD BCRPBC181420."

IO biomarker • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER

Newly-designed selective estrogen receptor downregulators and their role in the tumor microenvironment and hematopoiesis in breast malignancies (AACR 2026) - "Our newly-designed selective estrogen receptor down-regulator JD128 (SERDs) markedly reduces in vitro proliferation of several ERα+ BC cell lines, alone and combined with CDK 4/6 inhibitors, when compared with FDA-approved SERDs Fulvestrant and Elacestrant (P< 0.01). These estrogen-mediated effects on hematopoietic cell expansion/activation have implications for potential clinical use of SERDs in ER-positive or ER-negative BCs. [Funded by: CIRM DISC2-14166, UCLA JCCC Breast Cancer Award, Tower Cancer Research Foundation, Hickey Foundation, NIH/NCI U54 CA143930 CDU-UCLA JCCC Partnership, CBCRP B27IB3869, DOD BCRP Level 2-BC181420]"

Biomarker • IO biomarker • Tumor microenvironment • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD34 • ER

Real-World Evidence for 10 Oncology Drugs Approved in the last 5 years: A Comprehensive Narrative Synthesis. (PubMed, Crit Rev Oncol Hematol) - "RWE confirms the effectiveness and safety of multiple recently approved oncology drugs reinforcing the external validity of RCTs."

HEOR • Journal • Real-world evidence • Review • Breast Cancer • Endometrial Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • ER • HER-2 • MSI

A Computational Strategy to Identify Hub Genes in Pathway Analysis of Gamma Tocotrienol-treated MCF-7 Cells and Molecular Docking Study Using Selected Phytochemicals as Therapeutic Agents. (PubMed, Curr Med Chem) - "These findings may facilitate the development of traditional medicinebased therapeutic strategies and provide insights for potential lead optimization in breast cancer drug discovery."

Journal • Breast Cancer • Oncology • Solid Tumor • EGR1

Phase II study evaluating the addition of Elacestrant to Olaparib compared to Olaparib monotherapy in patients with HR+/HER2- locally advanced or metastatic breast cancer with germline BRCA1/2 mutations – ELEMENT (DKK 2026) - "To date, ten pts have been successfully enrolled across 34 active GBG sites. Further trial sites are currently being activated."

Clinical • Metastases • Monotherapy • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA • BRCA1 • BRCA2 • 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 (MBCC 2026) - No abstract available

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

ADELA: Elacestrant + Everolimus in Patients ER+/HER2-, ESR1mut, Advanced Breast Cancer Progressing to ET and CDK4/6i. (clinicaltrials.gov) - P3 | N=240 | Recruiting | Sponsor: MedSIR | Active, not recruiting ➔ Recruiting

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

ELECTRA: An open-label, multicenter, phase 1b/2 study of elacestrant in combination with abemaciclib in patients with brain metastasis from ER+/HER2- breast cancer (MBCC 2026) - No abstract available

Clinical • Combination therapy • P1/2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Ph 2 Elacestrant in ER Positive Uterine Sarcomas (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Dana-Farber Cancer Institute

New P2 trial • Endometrial Cancer • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor • Uterine Cancer • Uterine Leiomyosarcoma • ER

Molecular testing in breast cancer: The key to more personalized and effective therapies (DKK 2026) - P2, P4 | "Clinical Relevance: For pts with hereditary BRCA1/2 mutations, studies such as OlympiA, OlympiAD, and EMBRACA have demonstrated significant benefits of PARP inhibitors (olaparib, talazoparib), including a reduction in recurrence risk and improved survival in both early and metastatic disease. Somatic mutation analyses further expand therapeutic opportunities: ESR1 mutations support the use of modern endocrine therapies with SERDs (e.g., elacestrant), while alterations in the PI3K/AKT signaling pathway (PIK3CA, AKT1, PTEN) indicate eligibility for novel agents such as inavolisib or capivasertib... Molecular testing is crucial for the implementation of personalized treatment concepts in breast cancer. Early detection of germline and tumor mutations secures access to targeted therapies and improves pts prognosis."

Breast Cancer • Oncology • Solid Tumor • AKT1 • BRCA1 • BRCA2 • ER • PALB2 • PIK3CA • PTEN

Real-World Data and testing patterns for the treatment in metastatic HR+/HER2– breast cancer: Insights from the AGO QS-Mamma Registry (DKK 2026) - "2nd-line showed more variation: 24% CDK4/6i, 21% chemotherapy, 19% VEGFi, 11% Elacestrant, 17% PI3K-targeting therapy, 3% Olaparib. Improving testing strategies, especially in endocrine-pretreated patients, is key to personalizing treatment and optimizing outcomes. Real-world data can guide further integration of precision oncology."

Clinical • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA • ER • HER-2 • PIK3CA

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 study (MBCC 2026) - No abstract available

Clinical • Combination therapy • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

ADELA: A Double-blind, Placebo-controlled, Randomized Phase 3 Trial of Elacestrant + Everolimus Versus Elacestrant + Placebo in ER+/HER2- Advanced Breast Cancer (aBC) Patients with ESR1-mutated Tumors Progressing on Endocrine Therapy (ET) + CDK4/6i (MBCC 2026) - No abstract available

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