Inluriyo (imlunestrant) / Eli Lilly - LARVOL DELTA

Imlunestrant Exposure-Response (E-R) Analyses in Patients (Pts) with Advanced/Metastatic Breast Cancer (MBC) (ESMO 2026) - No abstract available

Clinical • Metastases • Breast Cancer • Oncology • Solid Tumor

Imlunestrant with or without abemaciclib in advanced breast cancer (ABC): Updated efficacy results from the phase 3 EMBER-3 trial (SABCS 2025) - "Background: At the primary progression-free survival (PFS) analysis, the phase 3 EMBER-3 trial in patients (pts) with ER+, HER2- ABC demonstrated significant PFS benefit with imlunestrant (imlu) vs standard therapy (SOC: fulvestrant or exemestane) in pts with ESR1 mutations (ESR1m), and with imlunestrant+abemaciclib (imlu+abema) vs imlu in all pts, regardless of ESR1m status. At a median follow-up of 28.5 months, a clinically meaningful improvement in OS was observed with imlu vs SOC in pts with ESR1m (corresponding to a numeric increase in mOS of 11.4 months), however, the boundary for significance was not achieved. Also, a favorable OS trend emerged with imlu+abema vs imlu in all pts, regardless of ESR1m. Sustained benefit in PFS, with clinically meaningful improvement in TTC, and PFS2 further highlight the efficacy of imlu-based regimens."

Clinical • Metastases • P3 data • Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Imlunestrant, an Oral Selective Estrogen Receptor Degrader (SERD), as Monotherapy and Combined with Abemaciclib, for Patients w/ ER+, HER2- Advanced Breast Cancer (ABC), Pretreated w/ Endocrine Therapy (ET): Results of the Phase 3 EMBER-3 trial. (SABCS 2024) - P3 | "Pts were randomized 1:1:1 to imlunestrant (400 mg once daily [QD]), physician’s choice standard-of-care (SOC) ET (fulvestrant or exemestane per label), or imlunestrant (400 mg QD) + abemaciclib (150 mg twice daily). Imlunestrant significantly improved PFS vs SOC in pts with ESR1m, and imlunestrant + abemaciclib significantly improved PFS vs imlunestrant in all pts regardless of ESR1m status. Imlunestrant had a favorable safety profile alone and combined with abemaciclib, thus providing an all-oral targeted therapy option for ET-pretreated pts with ER+, HER2- ABC."

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

Oral selective estrogen receptor degraders in ER+/HER2- breast cancer: a systematic review with pooled analysis of metastatic randomized trials and narrative synthesis of adjuvant evidence. (PubMed, Front Oncol) - "We searched PubMed, Cochrane CENTRAL, and conference abstract archives (SABCS, ESMO, ASCO; 2020-2026) for Phase II/III randomized controlled trials comparing oral SERDs (giredestrant, imlunestrant, elacestrant, camizestrant, vepdegestrant, amcenestrant) with standard endocrine therapy in ER-positive, HER2-negative breast cancer. This evidence synthesis across the full breast cancer continuum offers a framework for clinical decision-making as oral SERDs expand from advanced to early-stage disease. https://www.crd.york.ac.uk/prospero/display_record.php, identifier CRD420261358420."

Journal • Retrospective data • Review • 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 • Targeted Protein Degradation • ER • HER-2

Imlunestrant (Imlu) with or without abemaciclib (Abema) in advanced breast cancer (ABC): A subgroup analysis in CDK4/6 inhibitor (CDK4/6i)-pretreated patients (pts) from EMBER-3 (ESMO-BC 2025) - P3 | "The EMBER-3 trial reported significant PFS improvement with imlu over standard therapy (SOC; fulvestrant [fulv] or exemestane) in pts with ESR1 mutations (m), as well as with imlu + abema over imlu in all pts, regardless of ESR1m. In pts with ER+, HER2- ABC who have progressed on prior CDK4/6i, imlu+abema showed a consistent benefit over imlu, regardless of clinico-genomic factors. EMBER-3 is the 1st phase III trial to show benefit of an oral SERD + CDK4/6i after disease progression on prior CDK4/6i."

Clinical • Metastases • Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Oral SERDs: Transforming the treatment of advanced breast cancer-Insights from EMBER-3. (PubMed, Med) - "The phase 3 EMBER-3 trial1 demonstrated that when compared to standard therapy, imlunestrant improved progression-free survival (PFS) in advanced ER+/HER2- breast cancer with ESR1 mutations. When combined with abemaciclib, it significantly improved PFS for the entire population. However, the absence of a biomarker-based control group limits broader conclusions, highlighting the need for trials incorporating specific standards in ER+/HER2- breast cancer."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

SIERRA: Imlunestrant/Abemaciclib/Selinexor in Ovarian and Endometrial (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Dana-Farber Cancer Institute

New P2 trial • Endometrial Adenocarcinoma • Endometrial Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • TP53

Imlunestrant, an oral selective estrogen receptor degrader (SERD), in combination with human epidermal growth factor receptor 2 (HER2) directed therapy, with or without abemaciclib, in estrogen receptor (ER) positive, HER2 positive advanced breast cancer (aBC): EMBER phase 1a/1b study. (ASCO 2024) - P1 | "Key eligibility (Part C): ≥ 2 prior HER2 directed regimens, no prior CDK4/6i or fulvestrant; (Part E): received 1 st line induction taxane chemotherapy (any duration) + H + P, without disease progression and ≤1 prior therapy for aBC. Imlunestrant in combination with trastuzumab ± abemaciclib or pertuzumab was well tolerated, showed no drug-drug interactions, and demonstrated preliminary antitumor activity in pts with ER+/HER2+ aBC."

Combination therapy • Metastases • P1 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Fatigue • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Musculoskeletal Pain • Neutropenia • Oncology • Solid Tumor • CDK4 • ER • GATA3 • PIK3CA • TP53

Imlunestrant with or without everolimus or alpelisib, in ER+, HER2- advanced breast cancer (aBC): Results from the phase Ia/b EMBER study (ESMO 2023) - P1a/1b | "In the first-in-human phase 1a/b EMBER study, imlunestrant demonstrated favorable safety, pharmacokinetics (PK), and clinical benefit rate when administered as monotherapy (Jhaveri ASCO 2022) or with abemaciclib (Jhaveri SABCS 2022)...Median number of prior aBC therapies in combination cohorts was: 1 (range 1-2); including prior ET (100%), CDK4/6i (100%), fulvestrant (35%) and chemo (17%)...Conclusions Imlunestrant alone or in combination with everolimus or alpelisib demonstrated robust efficacy in pts with pre-treated ER+, HER-2 aBC. Toxicities were consistent with the known safety profile of both alpelisib and everolimus."

Metastases • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • PIK3CA

Circulating Tumour DNA (ctDNA) Dynamics From Patients With ER+, HER2- Advanced Breast Cancer in the Phase 3 EMBER-3 Trial (SABCS 2025) - "Background: The EMBER-3 trial, which included patients with ER+/HER2- advanced breast cancer previously treated with endocrine therapy (ET), demonstrated a significant improvement in progression-free survival (PFS) with imlunestrant (imlu) over standard ET (SOC ET, fulvestrant or exemestane) in patients with ESR1 mutations (ESR1m). Analyses of early ctDNA dynamics from EMBER-3 demonstrated greater early ctDNA reduction with imlunestrant compared with SOC ET in patients with ESR1m. The addition of abemaciclib to imlunestrant enhanced ctDNA decline in all patients, consistent with the primary study outcomes. Furthermore, while a ≥50% decline in ctDNA at C2D21 was associated with improved PFS, the allocated treatment remained a key determinant of patient outcomes."

Circulating tumor DNA • 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 • ER • HER-2

Imlunestrant plus abemaciclib versus fulvestrant plus abemaciclib in ER-positive, HER2-negative advanced breast cancer: an indirect treatment comparison of three phase III trials. (PubMed, ESMO Open) - "In this ITC analysis of patient-level data from three phase III trials, although not powered for formal hypothesis testing, the all-oral targeted combination therapy imlunestrant + abemaciclib showed a consistent numerical reduction in the risk of disease progression or death compared with fulvestrant + abemaciclib in patients with ER-positive/HER2-negative ABC previously treated with endocrine therapy ± CDK4/6i."

Journal • P3 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

Imlunestrant, an Oral Selective Estrogen Receptor Degrader, as Monotherapy and in Combination With Targeted Therapy in Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Phase Ia/Ib EMBER Study. (PubMed, J Clin Oncol) - "Imlunestrant, as monotherapy or in combination with targeted therapy, had a manageable safety profile with evidence of preliminary antitumor activity in ER+/HER2- ABC."

Combination therapy • Journal • Metastases • Monotherapy • P1 data • Breast Cancer • Endometrial Cancer • Fatigue • 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

Imlunestrant with or without Abemaciclib in Advanced Breast Cancer. (PubMed, N Engl J Med) - P3 | "Among patients with ER-positive, HER2-negative advanced breast cancer, treatment with imlunestrant led to significantly longer progression-free survival than standard therapy among those with ESR1 mutations but not in the overall population. Imlunestrant-abemaciclib significantly improved progression-free survival as compared with imlunestrant, regardless of ESR1-mutation status. (Funded by Eli Lilly; EMBER-3 ClinicalTrials.gov number, NCT04975308.)."

Journal • 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 • HER-2

Patient-reported outcomes (PROs) in patients with ER+, HER2- advanced breast cancer (ABC) treated with imlunestrant, investigator’s choice standard endocrine therapy, or imlunestrant + abemaciclib: Results from the phase III EMBER-3 trial. (ASCO 2025) - P3 | "The EMBER-3 trial, in patients (pts) with ER+, HER2- ABC who had disease progression on or after aromatase inhibitor-based therapy, showed significant progression free survival (PFS) improvement with imlu vs standard therapy (SOC, fulvestrant or exemestane) in pts with ESR1 mutations (ESR1m), and with imlunestrant+abemaciclib (imlu+abema) vs imlu in all pts, regardless of ESR1m. PROs from EMBER-3 demonstrated that patients with ESR1m had better GHS/QOL and PF with imlu vs SOC, mirroring efficacy results. While the frequency of CTCAE defined ISRs was low, the high rate of PRO-CTCAE ISR demonstrates that this clinically relevant adverse event is underappreciated by physicians. Additionally, all pts had generally comparable GHS/QOL and PF with imlu+abema vs imlu."

Clinical • Metastases • P3 data • Patient reported outcomes • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Pain • Solid Tumor • ER • HER-2

FDA approves imlunestrant in combination with abemaciclib for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer (FDA) - "Efficacy was evaluated in EMBER-3 (NCT04975308), a randomized, open-label, active-controlled, multicenter trial that enrolled 874 adults with ER-positive, HER2-negative, locally advanced or metastatic breast cancer previously treated with an aromatase inhibitor either alone or in combination with a CDK4/6 inhibitor...The recommended dosage of imlunestrant is 400 mg orally once daily (on an empty stomach at least two hours before food or one hour after food) and the recommended dosage of abemaciclib in combination is 150 mg orally twice daily (with or without food) until disease progression or unacceptable toxicity."

FDA approval • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Oral selective estrogen receptor degraders and biomarker-driven therapy in ER-positive breast cancer: mechanisms, clinical evidence, and future directions. (PubMed, Front Oncol) - "This review comprehensively examines the mechanisms of SERD action, their role in overcoming resistance to conventional endocrine therapy, and clinical applications of approved agents including fulvestrant, elacestrant, imlunestrant, and vepdegestrant, the first FDA-approved PROTAC estrogen receptor degrader. We discuss emerging oral SERDs such as giredestrant and camizestrant, novel PROTAC-based approaches, and combination strategies with CDK4/6 inhibitors, PI3K inhibitors, and other targeted agents. Special attention is given to ESR1 mutations as biomarkers for patient selection and therapy optimization. The review highlights key clinical trials including EMERALD, EMBER-3, SERENA-6, and lidERA that have shaped current treatment guidelines and points toward future directions in SERD development."

Biomarker • Journal • Review • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Gynecology • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • ER

Novel Endocrine Therapies: Current Status and Future Directions. (PubMed, Clin Breast Cancer) - "This review outlines key findings from clinical trials of Food and Drug Administration (FDA)-approved selective estrogen receptor degraders (SERDS), including elacestrant and imlunestrant, the newly FDA-approved proteolysis-targeting chimera (PROTAC) vepdegestrant, as well as emerging oral SERDs, PROTACs, complete estrogen receptor antagonists, selective estrogen receptor covalent antagonists (SERCAs), and other targeted therapies. We explore their mechanisms, efficacy, tolerability, and potential to improve treatment options and outcomes in both metastatic and early-stage disease."

Journal • Review • Breast Cancer • Estrogen Receptor Positive 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 • Targeted Protein Degradation • HER-2

Imlunestrant and Abemaciclib for the Treatment of Estrogen Receptor Positive Breast Cancer in Patients With Minimal Residual Disease, MIRI Trial (clinicaltrials.gov) - P2 | N=42 | Recruiting | Sponsor: Jonsson Comprehensive Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Minimal residual disease • 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 • HER-2 • PGR

Imlunestrant: Completion of P3 EMBER-3 trial (NCT04975308) with ER+, HER2- advanced breast cancer in Aug 2027 (Eli Lilly) - Q2 2026 Results: Primary completion of P3 EMBER-4 trial (NCT05514054) for breast neoplasms in Oct 2027; Completion of P3 EMBER-4 trial for breast neoplasms in Mar 2032

Trial completion date • Trial primary completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Oncology

Pharmacokinetic Drug-Drug Interactions of Imlunestrant in Healthy Female Participants of Nonchildbearing Potential. (PubMed, Clin Transl Sci) - "Participants tolerated imlunestrant at 200-800-mg doses, alone or with a CYP3A inhibitor (itraconazole), CYP3A inducer (carbamazepine), P-glycoprotein (P-gp) inhibitor (quinidine), and substrates of CYP2C8 (repaglinide), CYP2C19 (omeprazole), CYP2D6 (dextromethorphan), CYP3A (midazolam), P-gp (digoxin), and BCRP (rosuvastatin). Imlunestrant had no DDIs with CYP2C8 (repaglinide), CYP2C19 (omeprazole), and CYP3A4 (midazolam) substrates, or a P-gp inhibitor (quinidine), but weakly inhibited dextromethorphan (CYP2D6 substrate), digoxin (P-gp substrate), and rosuvastatin (BCRP substrate) clearance. Thus, considerations should be taken when imlunestrant is coadministered with strong CYP3A4 inhibitors, strong CYP3A4 inducers, and CYP2D6 and P-gp substrates where small changes in exposure may lead to toxicities."

Journal • PK/PD data • Breast Cancer • Constipation • Gastroenterology • Gastrointestinal Disorder • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Pain • Solid Tumor • CYP2C19 • ER • HER-2

Precision Endocrine-Based Combinations After CDK4/6 Inhibitor Progression in HR-Positive Metastatic Breast Cancer. (PubMed, Drug Des Devel Ther) - "Oral selective estrogen receptor degraders (SERDs), particularly elacestrant and imlunestrant, have demonstrated clinically meaningful efficacy in patients with ESR1-mutant tumors progressing after CDK4/6 inhibitors. Additionally, targeted inhibitors of the PI3K and AKT pathways, such as alpelisib and capivasertib, when combined with appropriate endocrine backbones, have been shown to overcome resistance mechanisms.The emergence of circulating tumor DNA (ctDNA) testing has further refined therapeutic decision-making by enabling real-time detection of resistance mutations and guiding directed treatment selection. Several prospective trials have demonstrated that molecularly guided switching of endocrine therapy can delay clinical progression and extend disease control, highlighting a shift toward precision-based, adaptive strategies.Collectively, these advances support a new treatment paradigm in which endocrine-based combinations remain the preferred approach after..."

Journal • Review • 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

PIKASSO-01: A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors (clinicaltrials.gov) - P1 | N=260 | Recruiting | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Recruiting | N=193 ➔ 260

Enrollment change • Enrollment open • Monotherapy • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

Evaluation of Pharmacokinetics and Safety of Imlunestrant in Participants with Hepatic Impairment. (PubMed, J Clin Pharmacol) - "Treatment-related adverse events were reported by two participants, one each from the moderate and severe hepatic impairment groups. This data will inform the recommendations for dosing patients with hepatic impairment under treatment with imlunestrant."

Journal • PK/PD data • Hepatology • Pain

Abemaciclib in HR+, HER2- Breast Cancer: A Narrative Review of the Clinical Evidence. (PubMed, Oncol Ther) - "Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, such as abemaciclib, ribociclib, and palbociclib, are used in combination with ET as a standard of care first-line option in HR+, HER2- advanced disease to improve survival outcomes...Abemaciclib has also been shown to be effective when combined with a variety of ET options, including aromatase inhibitors, tamoxifen, fulvestrant, imlunestrant, or as monotherapy, and has shown efficacy regardless of prior CDK4/6 inhibitor exposure, ESR1 or PI3K pathway mutational status, menopausal status, and in both endocrine-sensitive and endocrine-resistant breast cancer. Importantly, the safety profile of abemaciclib has been consistent across trials and allows the administration of the drug over long periods of time when needed, particularly if dose-reduction strategies are employed. Together, the data summarized in this publication help inform clinical decision making regarding the role of abemaciclib in the treatment of patients..."

Journal • Review • 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

Imlunestrant - ER+/HER2-, locally advanced or metastatic breast cancer with an activating ESR1 mutation (PubMed, Bull Cancer) - No abstract available

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