Inluriyo (imlunestrant) / Eli Lilly - LARVOL DELTA

CR11: Imlunestrant (imlu) with or without abemaciclib (abema) in advanced breast cancer (ABC): Safety analyses from the phase III EMBER-3 trial (HOPA 2026) - P3 | "The EMBER-3 trial (NCT04975308) in patients (pts) with ER+, HER2- ABC and disease progression on/after aromatase inhibitor therapy showed significant PFS improvement with imlu (400 mg once daily [QD]) over standard therapy (SOC, fulvestrant or exemestane) among pts with ESR1 mutations, as well as with imlu (400 mg QD) + abema [150 mg BID]) over imlu in all pts regardless of ESR1 mutation status1. Imlu had a favorable safety profile, similar to SOC, with mostly G1 AEs. Safety of imlu+abema was consistent with the known abema profile, without additive toxicity. AEs were manageable with supportive medications and/or dose adjustments, resulting in few discontinuations in all arms."

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

Imlunestrant With or Without Abemaciclib in Advanced Breast Cancer: Safety Analyses From the Phase 3 EMBER-3 Trial (HOPA 2026) - P3 | "The EMBER-3 trial (NCT04975308) in patients with ER-positive, HER2-negative advanced breast cancer and disease progression on or after aromatase inhibitor therapy showed significant improvement in progression-free survival with imlunestrant (400 mg once daily) over standard of care (SOC; fulvestrant or exemestane) among patients with ESR1 mutations, as well as with imlunestrant (400 mg once daily) plus abemaciclib (150 mg twice daily) over imlunestrant in all patients, regardless of ESR1 mutation status.1 The detailed safety analyses are presented. Imlunestrant had a favorable safety profile, similar to SOC, with predominantly grade 1 AEs. The safety of imlunestrant plus abemaciclib was consistent with the known abemaciclib profile, without additive AEs. The AEs were manageable with supportive medications and/or dose adjustments, resulting in few treatment discontinuations in all arms."

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

Characterization of LY4257496, a novel GRPR antagonist radiolabeled with lutetium-177 (AACR 2026) - P1 | "Efficacy was additive when 20MBq (Q14DX2) LY4257496 dose was given in combination with standard-of-care (SoC) therapies including imlunestrant, fulvestrant, and abemaciclib resulting in 40, 32, and 38% tumor regression, respectively at end of treatment (day 28). A competitive binding assay revealed that LY4257496 specifically bound to GRPR in human, mouse, and rat at comparable nanomolar potency of 8.5, 7.2, and 10.6 nM respectively. In biodistribution analyses, LY4257496 exhibited favorable pharmacokinetics with rapid tumor targeting and prolonged retention (% ID/g 22.6 at 1h, 11.6 at 24h), fast clearance from normal organs (all tissues below 3.5 % ID/g at 24h), and > 50% renal excretion. LY4257496 was well tolerated at 10, 20 and 30MBq (Q14DX2), and efficacy was dose dependent in T47D xenografts (26, 72, and 72 % TGI, respectively)."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • GRP-10 • HER-2 • PIK3CA

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

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

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

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

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

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

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

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

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 (MBCC 2026) - No abstract available

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 • Solid Tumor • ER • HER-2

Imlunestrant (imlu) with or without abemaciclib (abema) in advanced breast cancer (ABC): Safety analyses from the phase III EMBER-3 trial (MBCC 2026) - No abstract available

Clinical • Metastases • P3 data • Breast Cancer • Oncology • Solid Tumor

Imlunestrant plus abemaciclib versus fulvestrant plus abemaciclib in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (ABC): An indirect treatment comparison (ITC) of three phase 3 trials (MBCC 2026) - No abstract available

Metastases • 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

Imlunestrant with or without abemaciclib in advanced breast cancer (ABC): a subgroup analysis in CDK4/6 inhibitor (CDK4/6i)-pretreated patients from EMBER-3 (MBCC 2026) - No abstract available

Clinical • Metastases • Breast Cancer • Oncology • Solid Tumor

Imlunestrant with or without abemaciclib in advanced breast cancer: Updated efficacy results from the phase 3 EMBER-3 trial (MBCC 2026) - No abstract available

Clinical • Metastases • P3 data • Breast Cancer • Oncology • Solid Tumor

Imlunestrant with or without abemaciclib as first- and second-line therapy in advanced breast cancer (ABC): a subgroup analysis from the EMBER-3 trial (MBCC 2026) - No abstract available

Clinical • Metastases • Breast Cancer • Oncology • Solid Tumor

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

Imlunestrant (imlu) with or without abemaciclib (abema) in advanced breast cancer (ABC): Updated efficacy results from the phase 3 EMBER-3 trial (DKK 2026) - "At primary PFS analysis, the phase 3 EMBER-3 trial in patients (pts) with ER+, HER2- ABC demonstrated PFS benefit for imlu vs SOC (fulvestrant/exemestane) in pts with ESR1m, and with imlu+abema vs imlu in all pts, regardless of ESR1m status. Sustained benefit in PFS highlights the efficacy of imlu-based regimens. These updated data reinforce the potential of imlu, as monotherapy or with abema, as an all-oral chemotherapy-free option for ET-pretreated pts with ER+, HER2- ABC."

Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Patient-reported outcomes in patients with ER+, HER2- advanced breast cancer treated with imlunestrant, investigator's choice standard endocrine therapy, or imlunestrant+abemaciclib: Results from the phase III EMBER-3 trial (DKK 2026) - "In EMBER-3, patients (pts) with ER+, HER2- advanced breast cancer (ABC) with disease progression on or after aromatase inhibitor-based therapy, achieved significant PFS improvement with imlunestrant (imlu) vs standard therapy (SOC: fulvestrant/exemestane) in pats with ESR1 mutations (ESR1m), and with imlu+abemaciclib (abema) vs imlu in all pts, regardless of ESR1m. The importance of ISR as a clinically relevant AE is demonstrated by the high incidence of pt-reported ISR with fulvestrant. These results support the efficacy and safety of imlu as monotherapy or combined with abema as an all-oral targeted therapy option."

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 • Solid Tumor • ER • HER-2

Imlunestrant (imlu) with or without abemaciclib (abema) in advanced breast cancer (ABC): Safety analyses from the phase III EMBER-3 trial (DKK 2026) - P3 | "The EMBER-3 trial (NCT04975308) in patients (pts) with ER+, HER2- ABC and disease progression on/after aromatase inhibitor therapy showed significant PFS improvement with imlu (400 mg once daily [QD]) over standard therapy (SOC, fulvestrant or exemestane) among pts with ESR1 mutations, as well as with imlu (400 mg QD) + abema [150 mg BID]) over imlu in all pts regardless of ESR1 mutation status. AEs were manageable with supportive medications and/or dose adjustments, resulting in few discontinuations in all arms. Imlu alone or with abema, provides a safe, tolerable, all-oral targeted therapy option for pts with ER+, HER2- ABC."

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

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 estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (ABC): An indirect treatment comparison (ITC) of three phase 3 trials (DKK 2026) - "Although not powered for formal hypothesis testing, PFS favored imlu+abema vs fulv+abema across all three ITC methods including Bucher [E3: effective sample size (ESS)=426, pooled M2/pM: ESS=1037 (HR:0.77; 95% CI:0.58, 1.04)], MAIC [E3: ESS=426, pooled M2/pM: ESS=473 (HR:0.77; 95% CI:0.55, 1.06)] and PSM [E3: ESS=343, pooled M2/pM: ESS=343 (HR:0.83; 95% CI:0.56, 1.22)]. In this exploratory ITC analysis, the all-oral targeted therapy imlu+abema showed a consistent numerical PFS benefit compared with fulv+abema in patients with ER+, HER2ABC previously treated with endocrine therapy (ET) ± CDK4/6i."

Metastases • 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

Imlunestrant with or without Abemaciclib in Advanced Breast Cancer (ABC): A Subgroup Analysis in CDK4/6 inhibitor (CDK4/6i)-pretreated patients from EMBER-3 (DKK 2026) - "The EMBER-3 trial reported significant PFS improvement with imlu over standard therapy (SOC; fulvestrant or exemestane) in patients (pts) with ESR1-mutations (m), and with imlu+abemaciclib (abema)over imlu in all pts, regardless of ESR1m. Benefit was observed regardless of prior CDK4/6i duration or type, though analyses of prior abema pts were limited by a small sample size.In pts with ER+, HER2- ABC who have progressed on prior CDK4/6i, imlu+abema showed a consistent benefit over imlut, regardless of clinico-genomic factors. EMBER-3 is the 1st phase 3 trial to show benefit of an oral SERD+CDK4/6i after disease progression on prior CDK4/6i."

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

A Systematic Review of Major Advances in Breast Cancer Therapeutics in 2025: Synthesis of Conference and Published Evidence. (PubMed, Int J Mol Sci) - "Key 2025 findings (50 clinical trials) include: (1) confirmation of overall survival benefit with adjuvant CDK4/6 inhibitors in HR+/HER2- early breast cancer (monarchE: HR = 0.842, p = 0.0273); (2) establishment of trastuzumab deruxtecan (T-DXd) as a new standard in high-risk HER2+ early disease (DESTINY-Breast05: IDFS HR = 0.47) and first-line metastatic settings (DESTINY-Breast09: PFS HR = 0.58); (3) validation of TROP2-directed ADCs as first-line therapy for metastatic triple-negative breast cancer (ASCENT-03: PFS HR = 0.62; BEGONIA: ORR 79%); (4) paradigm shift to proactive, liquid biopsy-guided therapy switching (SERENA-6: PFS HR = 0.44); (5) updated efficacy and safety of the oral SERD imlunestrant from the EMBER-3 trial, supporting its role in ESR1-mutated advanced breast cancer and in combination with abemaciclib; (6) confirmation of long-term survival benefit for neoadjuvant carboplatin in early TNBC and new positive adjuvant data; (7) pivotal advances in HER2+..."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • Triple Negative Breast Cancer • ER